Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| I2I-MC-JMMG | Other Identifier | Eli Lilly and Company |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
LY2603618 is a selective inhibitor of the deoxyribonucleic acid (DNA) damage checkpoint kinase 1 (CHK1). It was being developed as a chemotherapeutic-enhancing agent in the treatment of cancer. Phase 1 studies have shown the feasibility of combining LY2603618 with either gemcitabine or pemetrexed. The objective of this study was to find the dose of LY2603618 that can be safely combined with standard doses of pemetrexed and cisplatin and to test if this triplet offered a significant improvement in progression-free survival (PFS) in participants with Stage IV nonsquamous non-small cell lung cancer (NSCLC) in the first-line of palliative treatment.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1: LY2603618 130 to 275 mg | Experimental | Cycle 1-2 (21-day cycle): Day 1: pemetrexed 500 milligrams per meter square (mg/m^2) + cisplatin 75 mg/m^2 Day 2: LY2603618 at 130-275 milligrams (mg) After 2 cycles, participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met. |
|
| Phase 2: Pemetrexed + Cisplatin + LY2603618 | Experimental | Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose from phase 1 portion of trial After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may continue on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion is met. Maintenance Therapy Experimental Arm (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, participant was in maintenance therapy and randomized to the experimental arm, the participant is eligible to continue with pemetrexed (Day 1)/LY2603618 (Day 2) therapy if the investigator deems it is in the best interest of the participant and the participant consents. |
|
| Phase 2: Pemetrexed + Cisplatin | Active Comparator | Cycle 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may continue on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion is met. Maintenance Therapy Comparator Arm: Phase 2 (every 21 days): Day 1: pemetrexed 500 mg/m^2 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pemetrexed | Drug | Administered intravenously as a continuous 10-minute infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase 2: Progression-Free Survival Time | Progression-free survival (PFS) time is defined as the time from the date of randomization to the first date of documented objective progressive disease (PD) or death from any cause. For participants who were not known to have had objective PD as of the data inclusion cut-off date for a particular analysis, PFS was censored at the date of the last objective progression-free disease assessments. For participants who took any subsequent systemic anticancer therapy prior to progression, PFS was censored at the date of the last objective progression-free disease assessment prior to the start date of any subsequent systemic anticancer therapy. PFS time was summarized using Kaplan-Meier estimates. | Randomization up to first date of PD or death from any cause (up to 6 months after the last participant entered treatment) |
| Phase 1: Recommended Phase 2 Dose of LY2603618 | The recommended Phase 2 dose for LY2603618 when administered approximately 24 hours after pemetrexed and cisplatin was based on the maximum tolerated dose (MTD) and achievement of predefined LY2603618 plasma systemic exposures targets (area under the LY2603618 plasma concentration versus time curve from time zero to infinity [AUC(0-∞)] >21,000 nanogram*hour/milliliter [ng*h/mL] and maximum LY2603618 plasma concentration [Cmax] >2000 nanograms/milliliter [ng/mL]). | Time of first dose to last dose |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 2: Overall Survival | Overall survival (OS) time is defined as the time from the date of randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participant was known to be alive prior to the data cut-off date. OS was summarized using Kaplan-Meier estimates. | Randomization to the date of death from any cause through the time of study discontinuation (approximately 12 months after last participant was randomized) |
| Measure | Description | Time Frame |
|---|---|---|
| Deaths | Deaths that occurred during the study are presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | Randomization through 12 months after the last participant was randomized |
Inclusion Criteria:
Phase 1 portion:
Phase 2 portion:
Phase 1 participants can have measurable or nonmeasurable disease. Phase 2 participants must have at least 1 measurable lesion according to Investigational New Drug (Response Evaluation Criteria in Solid Tumors [RECIST], v1.1) definitions. Tumor lesions located in a previously irradiated area can be considered measurable if they are new or if have shown unequivocal progression.
Have a performance status ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale
Have adequate hematologic, hepatic, and renal organ function
Prior radiation therapy for treatment of cancer is allowed to <25% of the bone marrow, and participants must have recovered from the acute toxic effects of their treatment prior to study enrollment. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 4 weeks before study entry
For women: Must be surgically sterile, postmenopausal, or compliant with a highly reliable contraceptive method (failure rate <1%) during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment and must not be breast-feeding. For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 6 months after the treatment period
Exclusion Criteria:
Have serious preexisting medical conditions or serious concomitant systemic disorders that would compromise the safety of the participant or his/her ability to complete the study, at the discretion of the investigator (for example, unstable angina pectoris or uncontrolled diabetes mellitus). Special attention should be paid to kidney and heart conditions that may be worsened with cisplatin treatment or hydration
Have central nervous system (CNS) metastases (unless the participant has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). A screening computed tomography scan or magnetic resonance imaging before enrollment in the absence of a clinical suspicion of brain metastases is not required.
Have current active infection that would, in the opinion of the investigator, compromise the participant's ability to tolerate therapy
Have known allergy to pemetrexed, cisplatin, LY2603618, or any ingredient of pemetrexed, cisplatin, or LY2603618
Have clinically significant (by physical exam) third-space fluid collections; for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry
Participants taking non-steroidal anti-inflammatory drugs who cannot interrupt the treatment appropriately according to the guidelines
Have received a recent yellow-fever vaccination (within 28 days of enrollment) or are receiving concurrent yellow-fever vaccination
Phase 1 portion:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY(1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Mannheim | Baden-Wurttemberg | 68167 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28625637 | Derived | Wehler T, Thomas M, Schumann C, Bosch-Barrera J, Vinolas Segarra N, Dickgreber NJ, Dalhoff K, Sebastian M, Corral Jaime J, Alonso M, Hynes SM, Lin J, Hurt K, Bence Lin A, Calvo E, Paz-Ares L. A randomized, phase 2 evaluation of the CHK1 inhibitor, LY2603618, administered in combination with pemetrexed and cisplatin in patients with advanced nonsquamous non-small cell lung cancer. Lung Cancer. 2017 Jun;108:212-216. doi: 10.1016/j.lungcan.2017.03.001. Epub 2017 Mar 6. | |
| 24942404 |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1: Pemetrexed + Cisplatin + LY2603618 | Cycles 1-2 (21-day cycle): Day 1: pemetrexed 500 milligrams per square meter (mg/m^2) + cisplatin 75 mg/m^2 Day 2: LY2603618 130 to 275 milligrams (mg) After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Pemetrexed, cisplatin, and LY2603618 were administered intravenously (IV) over 10 minutes, 1 hour, and 1 hour, respectively. |
| FG001 | Phase 2: Pemetrexed + Cisplatin + LY2603618 | Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively. |
| FG002 | Phase 2: Pemetrexed + Cisplatin | Cycles 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Day 1: pemetrexed 500 mg/m^2 Pemetrexed was administered IV over 10 minutes and cisplatin was administered IV over 1 hour. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All participants.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Phase 1: Pemetrexed + Cisplatin + LY2603618 | Cycles 1-2 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 130 to 275 mg After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Phase 2: Progression-Free Survival Time | Progression-free survival (PFS) time is defined as the time from the date of randomization to the first date of documented objective progressive disease (PD) or death from any cause. For participants who were not known to have had objective PD as of the data inclusion cut-off date for a particular analysis, PFS was censored at the date of the last objective progression-free disease assessments. For participants who took any subsequent systemic anticancer therapy prior to progression, PFS was censored at the date of the last objective progression-free disease assessment prior to the start date of any subsequent systemic anticancer therapy. PFS time was summarized using Kaplan-Meier estimates. | All randomized Phase 2 participants. | Posted | Median | 90% Confidence Interval | months | Randomization up to first date of PD or death from any cause (up to 6 months after the last participant entered treatment) |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase 1: Pemetrexed + Cisplatin + LY2603618 | Cycles 1-2 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 130 to 275 mg After 2 cycles, participants may have continued on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 16.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 16.1 | Systematic Assessment |
Enrollment was halted on 25 October 2012 due to a numerical imbalance in events of thromboembolic nature between the experimental arm and the control arm.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
Not provided
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D008654 | Mesothelioma |
| D002277 | Carcinoma |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068437 | Pemetrexed |
| D002945 | Cisplatin |
| C582547 | LY2603618 |
| ID | Term |
|---|---|
| D006147 | Guanine |
| D007042 | Hypoxanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Cisplatin | Drug | Administered intravenously as a continuous 1-hour infusion |
|
| LY2603618 | Drug | Administered intravenously as a continuous 1-hour infusion |
|
| Phase 2: Overall Tumor Response Rate: Percentage of Participants Who Achieved a Confirmed Best Response of Completed Response (CR) or Partial Response (PR) | Overall response rate is the best response of CR or PR as classified by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) guidelines. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100. | Randomization until date of disease progression (up to 6 months after the last participant was randomized) |
| Phase 2: Change in Tumor Size | Change in tumor size was based on tumor measurements collected according to RECIST, v1.1 guidelines. Tumor size is the sum of the tumor measurements (longest diameters) of target lesions at each tumor evaluation. Change in tumor size was defined as the change in log tumor size from baseline evaluation to the evaluation at the end of Cycle 2. | Baseline, end of Cycle 2 |
| Phase 1: Pharmacokinetic: Maximum Plasma Concentration (Cmax) (LY2603618) | Cmax is reported for each LY2603618 dose level on Cycle 1 /Day 2 and Cycle 2 /Day 2. The number of pharmacokinetic observations (n) used in the analysis is presented for each dose level and time point. | Cycle 1/Day 2 - immediately prior to end of LY2603618 infusion, and 1, 3, 6, 24, 48, 72, and 144 hours postdose; Cycle 2/Day 2 - predose, immediately prior to end of LY2603618 infusion, and 1, 3, 6, 24, 48, 72, and 144 hours postdose |
| Phase 1: Pharmacokinetic: Cmax (Pemetrexed and Cisplatin) | Cmax for pemetrexed and total platinum (t-platinum) from cisplatin is reported. The number of pharmacokinetic observations (n) used in the analysis is presented for each drug. | Pemetrexed: Cycle 1/Day 1 - immediately prior to end of pemetrexed infusion and 1, 2, 6 and 24 hours postdose. Cisplatin: Cycle 1/Day 1 - immediately prior to end of cisplatin infusion and 0.5, 1, 2, 6, 24, 72, 96, and 168 hours postdose. |
| Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618) | AUC from time zero to 24 hours (AUC[0-24]), AUC from time zero to the last time point with a measurable concentration (AUC[0-tlast]), and AUC from time zero to infinity (AUC[0-∞]) values are reported for each LY2603618 dose level on Cycle 1 /Day 2 and Cycle 2 /Day 2. The number of pharmacokinetic observations (n) used in the analysis is presented for each dose level and time point. | Cycle 1/Day 2 - immediately prior to end of LY2603618 infusion and 1, 3, 6, 24, 48, 72, and 144 hours postdose; Cycle 2/Day 2 - predose, immediately prior to end of LY2603618 infusion, and 1, 3, 6, 24, 48, 72, and 144 hours postdose |
| Phase 1: Pharmacokinetic: AUC (Pemetrexed and Cisplatin) | AUC(0-tlast) and AUC(0-∞) values are reported for pemetrexed and t-platinum from cisplatin. The number of pharmacokinetic observations (n) used in the analysis is presented for each drug. | Pemetrexed: Cycle 1/Day 1 - immediately prior to end of pemetrexed infusion and 1, 2, 6 and 24 hours postdose. Cisplatin: Cycle 1/Day 1 - immediately prior to end of cisplatin infusion and 0.5, 1, 2, 6, 24, 72, 96, and 168 hours postdose. |
| Phase 2: Pharmacokinetic: Cmax (LY2603618) | Cycle 1/Day 2 - predose, immediately prior to the end of the LY2603618 infusion, and 2-6, 24-48, and 72-96 hours postdose |
| Phase 2: Pharmacokinetic: AUC (LY2603618) | AUC (0-24), AUC(0-tlast), and AUC(0-∞) values are reported for LY2603618. The number of pharmacokinetic observations (n) used in the analysis is presented. | Cycle 1/Day 2 - predose, immediately prior to the end of the LY2603618 infusion, and 2-6, 24-48, and 72-96 hours postdose |
| Phase 2: Change From Baseline to Long-term Follow up in Lung Cancer Symptom Scale (LCSS) | Health-related quality of life and participant symptoms were assessed using the LCSS (patient scale). However, improper implementation of questionnaires at the site level reduced the sponsor's ability to accurately evaluate the impacted data. Therefore, the LCSS data should be interpreted with caution. The LCSS is a 9-item questionnaire. Six questions are symptom-specific measures for lung cancer (appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items describe total symptomatic distress, activity status, and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-milliliter (mm) lines. Scores range from 0 (for best outcome) to 100 (for worst outcome). The Average Symptom Burden Index (ASBI) was calculated as the mean of 6 symptom-specific questions from the LCSS. The total LCSS score was calculated as the mean of 9 questions from the LCSS. | Randomization to the end of study (approximately 12 months after the last participant entered treatment) |
| Phase 1: Document Any Antitumor Activity Per Radiological Scans and/or Tumor Markers | Overall response rate is presented. Overall response rate is defined as the percentage of participants with a best response of CR or PR as classified by the investigators according to RECIST, v1.1 criteria. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100. | Baseline through end of Phase 1 |
| Phase 2: Proportion of Participants Receiving Maintenance Therapy | Cycle 5 |
| Phase 2: Clinical Benefit Rate: Percentage of Participant Who Achieved a Response of Stable Disease (SD), Partial Response (PR), or Complete Response (CR) | Clinical benefit rate is the best response CR, PR, or SD as classified by the investigators according to the RECIST, v1.1 guidelines. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameter since treatment started. Clinical benefit rate is calculated as a total number of participants with CR, PR, or SD divided by the total number of participants with at least 1 measurable lesion, multiplied by 100. | Randomization until date of disease progression or death (up to 6 months after the last participant was randomized) |
| Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Münster | Nordhein-Westfalen | 48149 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Coswig | Saxony | 01640 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Berlin | 14165 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Frankfurt | 60596 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Hanover | 30625 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Heidelberg | 69126 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Homburg | 66421 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Immenhausen | 34376 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Lübeck | 23538 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Mainz | D-55131 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Rheine | 48431 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Ulm | 89081 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Mataró | Barcelona | 08304 | Spain |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Pozuelo de Alarcón | Madrid | 28223 | Spain |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Oviedo | Principality of Asturias | 33006 | Spain |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Barcelona | 08035 | Spain |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Barcelona | 08036 | Spain |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Barcelona | 08908 | Spain |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Girona | 17007 | Spain |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Madrid | 28034 | Spain |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Madrid | 28046 | Spain |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Madrid | 28050 | Spain |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Seville | 41013 | Spain |
| Derived |
| Calvo E, Chen VJ, Marshall M, Ohnmacht U, Hynes SM, Kumm E, Diaz HB, Barnard D, Merzoug FF, Huber L, Kays L, Iversen P, Calles A, Voss B, Lin AB, Dickgreber N, Wehler T, Sebastian M. Preclinical analyses and phase I evaluation of LY2603618 administered in combination with pemetrexed and cisplatin in patients with advanced cancer. Invest New Drugs. 2014 Oct;32(5):955-68. doi: 10.1007/s10637-014-0114-5. Epub 2014 Jun 20. |
| Withdrawal by Subject |
|
| Physician Decision |
|
| BG001 | Phase 2: Pemetrexed + Cisplatin + LY2603618 | Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively. |
| BG002 | Phase 2: Pemetrexed + Cisplatin | Cycles 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Day 1: pemetrexed 500 mg/m^2 Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
|
| Region of Enrollment | Count of Participants | Participants | No |
|
| Initial Pathological Diagnosis | Count of Participants | Participants | No |
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status | Eastern Cooperative Oncology Group (ECOG) Performance Status classifies participants according to their functional impairment. Scores range from 0 (Fully Active) to 5 (Death) as follows: 0 - Fully Active; 1 - Ambulatory, Restricted Strenuous Activity; 2 - Ambulatory, No Work Activities; 3 - Partially Confined to Bed, Limited Self Care; 4 - Completely Disabled; and 5 - Dead. | Count of Participants | Participants | No |
|
Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively. |
| OG001 | Phase 2: Pemetrexed + Cisplatin | Cycles 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Day 1: pemetrexed 500 mg/m^2 Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour. |
|
|
|
| Primary | Phase 1: Recommended Phase 2 Dose of LY2603618 | The recommended Phase 2 dose for LY2603618 when administered approximately 24 hours after pemetrexed and cisplatin was based on the maximum tolerated dose (MTD) and achievement of predefined LY2603618 plasma systemic exposures targets (area under the LY2603618 plasma concentration versus time curve from time zero to infinity [AUC(0-∞)] >21,000 nanogram*hour/milliliter [ng*h/mL] and maximum LY2603618 plasma concentration [Cmax] >2000 nanograms/milliliter [ng/mL]). | Phase 1 participants who received at least 1 dose of any of the study drugs. | Posted | Number | mg | Time of first dose to last dose |
|
|
|
| Secondary | Phase 2: Overall Survival | Overall survival (OS) time is defined as the time from the date of randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participant was known to be alive prior to the data cut-off date. OS was summarized using Kaplan-Meier estimates. | All randomized Phase 2 participants. | Posted | Median | 90% Confidence Interval | months | Randomization to the date of death from any cause through the time of study discontinuation (approximately 12 months after last participant was randomized) |
|
|
|
|
| Secondary | Phase 2: Overall Tumor Response Rate: Percentage of Participants Who Achieved a Confirmed Best Response of Completed Response (CR) or Partial Response (PR) | Overall response rate is the best response of CR or PR as classified by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) guidelines. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100. | All randomized Phase 2 participants. | Posted | Number | 90% Confidence Interval | percentage of participants | Randomization until date of disease progression (up to 6 months after the last participant was randomized) |
|
|
|
|
| Secondary | Phase 2: Change in Tumor Size | Change in tumor size was based on tumor measurements collected according to RECIST, v1.1 guidelines. Tumor size is the sum of the tumor measurements (longest diameters) of target lesions at each tumor evaluation. Change in tumor size was defined as the change in log tumor size from baseline evaluation to the evaluation at the end of Cycle 2. | Participants with measureable disease (target lesions) at baseline who received at least 1 dose of study drug. | Posted | Mean | Standard Deviation | centimeters | Baseline, end of Cycle 2 |
|
|
|
|
| Secondary | Phase 1: Pharmacokinetic: Maximum Plasma Concentration (Cmax) (LY2603618) | Cmax is reported for each LY2603618 dose level on Cycle 1 /Day 2 and Cycle 2 /Day 2. The number of pharmacokinetic observations (n) used in the analysis is presented for each dose level and time point. | Phase 1 participants who received at least 1 dose of LY2603618 and had samples collected for pharmacokinetic analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1/Day 2 - immediately prior to end of LY2603618 infusion, and 1, 3, 6, 24, 48, 72, and 144 hours postdose; Cycle 2/Day 2 - predose, immediately prior to end of LY2603618 infusion, and 1, 3, 6, 24, 48, 72, and 144 hours postdose |
|
|
|
| Secondary | Phase 1: Pharmacokinetic: Cmax (Pemetrexed and Cisplatin) | Cmax for pemetrexed and total platinum (t-platinum) from cisplatin is reported. The number of pharmacokinetic observations (n) used in the analysis is presented for each drug. | Phase 1 participants who received at least 1 dose of pemetrexed or cisplatin and had samples collected for pharmacokinetic analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pemetrexed: Cycle 1/Day 1 - immediately prior to end of pemetrexed infusion and 1, 2, 6 and 24 hours postdose. Cisplatin: Cycle 1/Day 1 - immediately prior to end of cisplatin infusion and 0.5, 1, 2, 6, 24, 72, 96, and 168 hours postdose. |
|
|
|
| Secondary | Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618) | AUC from time zero to 24 hours (AUC[0-24]), AUC from time zero to the last time point with a measurable concentration (AUC[0-tlast]), and AUC from time zero to infinity (AUC[0-∞]) values are reported for each LY2603618 dose level on Cycle 1 /Day 2 and Cycle 2 /Day 2. The number of pharmacokinetic observations (n) used in the analysis is presented for each dose level and time point. | Phase 1 participants who received at least 1 dose of LY2603618 and had samples collected for pharmacokinetic analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Cycle 1/Day 2 - immediately prior to end of LY2603618 infusion and 1, 3, 6, 24, 48, 72, and 144 hours postdose; Cycle 2/Day 2 - predose, immediately prior to end of LY2603618 infusion, and 1, 3, 6, 24, 48, 72, and 144 hours postdose |
|
|
|
| Secondary | Phase 1: Pharmacokinetic: AUC (Pemetrexed and Cisplatin) | AUC(0-tlast) and AUC(0-∞) values are reported for pemetrexed and t-platinum from cisplatin. The number of pharmacokinetic observations (n) used in the analysis is presented for each drug. | Phase 1 participants who received at least 1 dose of pemetrexed or cisplatin and had samples collected for pharmacokinetic analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Pemetrexed: Cycle 1/Day 1 - immediately prior to end of pemetrexed infusion and 1, 2, 6 and 24 hours postdose. Cisplatin: Cycle 1/Day 1 - immediately prior to end of cisplatin infusion and 0.5, 1, 2, 6, 24, 72, 96, and 168 hours postdose. |
|
|
|
| Secondary | Phase 2: Pharmacokinetic: Cmax (LY2603618) | Phase 2 participants who received at least 1 dose of LY2603618 and had samples collected for pharmacokinetic analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1/Day 2 - predose, immediately prior to the end of the LY2603618 infusion, and 2-6, 24-48, and 72-96 hours postdose |
|
|
|
| Secondary | Phase 2: Pharmacokinetic: AUC (LY2603618) | AUC (0-24), AUC(0-tlast), and AUC(0-∞) values are reported for LY2603618. The number of pharmacokinetic observations (n) used in the analysis is presented. | Phase 2 participants who received at least 1 dose of LY2603618 and had samples collected for pharmacokinetic analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Cycle 1/Day 2 - predose, immediately prior to the end of the LY2603618 infusion, and 2-6, 24-48, and 72-96 hours postdose |
|
|
|
| Secondary | Phase 2: Change From Baseline to Long-term Follow up in Lung Cancer Symptom Scale (LCSS) | Health-related quality of life and participant symptoms were assessed using the LCSS (patient scale). However, improper implementation of questionnaires at the site level reduced the sponsor's ability to accurately evaluate the impacted data. Therefore, the LCSS data should be interpreted with caution. The LCSS is a 9-item questionnaire. Six questions are symptom-specific measures for lung cancer (appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items describe total symptomatic distress, activity status, and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-milliliter (mm) lines. Scores range from 0 (for best outcome) to 100 (for worst outcome). The Average Symptom Burden Index (ASBI) was calculated as the mean of 6 symptom-specific questions from the LCSS. The total LCSS score was calculated as the mean of 9 questions from the LCSS. | All enrolled Phase 2 participants who had the baseline LCSS assessment and at least 1 post-baseline assessment. | Posted | Mean | Standard Deviation | units on a scale | Randomization to the end of study (approximately 12 months after the last participant entered treatment) |
|
|
|
| Secondary | Phase 1: Document Any Antitumor Activity Per Radiological Scans and/or Tumor Markers | Overall response rate is presented. Overall response rate is defined as the percentage of participants with a best response of CR or PR as classified by the investigators according to RECIST, v1.1 criteria. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100. | All randomized Phase 1 participants. | Posted | Number | 90% Confidence Interval | percentage of participants | Baseline through end of Phase 1 |
|
|
|
| Other Pre-specified | Deaths | Deaths that occurred during the study are presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | All enrolled participants. | Posted | Count of Participants | Participants | No | Randomization through 12 months after the last participant was randomized |
|
|
|
| Secondary | Phase 2: Proportion of Participants Receiving Maintenance Therapy | Zero participants analyzed. Treatment with LY2603618 was discontinued after 25 October 2012, data was not collected for analysis of the Phase 2: Proportion of Participants Receiving Maintenance Therapy. | Posted | Cycle 5 |
|
|
| Secondary | Phase 2: Clinical Benefit Rate: Percentage of Participant Who Achieved a Response of Stable Disease (SD), Partial Response (PR), or Complete Response (CR) | Clinical benefit rate is the best response CR, PR, or SD as classified by the investigators according to the RECIST, v1.1 guidelines. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameter since treatment started. Clinical benefit rate is calculated as a total number of participants with CR, PR, or SD divided by the total number of participants with at least 1 measurable lesion, multiplied by 100. | All randomized Phase 2 participants. | Posted | Number | 90% Confidence Interval | percentage of participants | Randomization until date of disease progression or death (up to 6 months after the last participant was randomized) |
|
|
|
|
| 1 |
| 14 |
| 14 |
| 14 |
| EG001 | Phase 2: Pemetrexed + Cisplatin + LY2603618 | Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 (275 mg) After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, the participant was in maintenance therapy and randomized to the experimental arm, the participant was eligible to continue with pemetrexed/LY2603618 therapy if the investigator deemed it was in the participant's best interest and the participant consented. Pemetrexed, cisplatin, and LY2603618 were administered IV over 10 minutes, 1 hour, and 1 hour, respectively. | 16 | 39 | 37 | 39 |
| EG002 | Phase 2: Pemetrexed + Cisplatin | Cycles 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may have continued on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion was met. Maintenance therapy (every 21 days): Day 1: pemetrexed 500 mg/m^2 Pemetrexed was administered IV over 10 minutes, and cisplatin was administered IV over 1 hour. | 6 | 22 | 22 | 22 |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Angina pectoris | Cardiac disorders | MedDRA 16.1 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 16.1 | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Death | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Urinary tract infection bacterial | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
|
| Tibia fracture | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 16.1 | Systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA 16.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 16.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 16.1 | Systematic Assessment |
|
| Ketoacidosis | Metabolism and nutrition disorders | MedDRA 16.1 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Metastases to bone | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.1 | Systematic Assessment |
|
| Metastatic pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.1 | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Ischaemic stroke | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 16.1 | Systematic Assessment |
|
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Ototoxicity | Ear and labyrinth disorders | MedDRA 16.1 | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA 16.1 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 16.1 | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA 16.1 | Systematic Assessment |
|
| Eye oedema | Eye disorders | MedDRA 16.1 | Systematic Assessment |
|
| Eyelid oedema | Eye disorders | MedDRA 16.1 | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA 16.1 | Systematic Assessment |
|
| Papilloedema | Eye disorders | MedDRA 16.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Catheter site related reaction | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Catheter site swelling | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Infusion site extravasation | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Infusion site pain | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Candida infection | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Eye infection | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Gingivitis | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Herpes simplex | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Laryngitis | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Paronychia | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Contrast media reaction | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 16.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 16.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 16.1 | Systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA 16.1 | Systematic Assessment |
|
| C-reactive protein increased | Investigations | MedDRA 16.1 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 16.1 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 16.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 16.1 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 16.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dyslipidaemia | Metabolism and nutrition disorders | MedDRA 16.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 16.1 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 16.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 16.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dysaesthesia | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Neurotoxicity | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Paresis | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 16.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 16.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 16.1 | Systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedDRA 16.1 | Systematic Assessment |
|
| Menstruation irregular | Reproductive system and breast disorders | MedDRA 16.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Erythema multiforme | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Skin disorder | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Catheterisation venous | Surgical and medical procedures | MedDRA 16.1 | Systematic Assessment |
|
| Circulatory collapse | Vascular disorders | MedDRA 16.1 | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA 16.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 16.1 | Systematic Assessment |
|
| Hypertensive crisis | Vascular disorders | MedDRA 16.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 16.1 | Systematic Assessment |
|
| Phlebitis | Vascular disorders | MedDRA 16.1 | Systematic Assessment |
|
Not provided
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D000236 | Adenoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D018301 | Neoplasms, Mesothelial |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D005971 | Glutamates |
| D024342 | Amino Acids, Acidic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000600 | Amino Acids, Dicarboxylic |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
|
| 185 mg, Cycle 1/Day 2 |
|
|
| 185 mg, Cycle 2/Day 2 |
|
|
| 240 mg, Cycle 1/Day 2 |
|
|
| 240 mg, Cycle 2/Day 2 |
|
|
| 275 mg, Cycle 1/Day 2 |
|
|
| 275 mg, Cycle 2/Day 2 |
|
|
|
| 130 mg, Cycle 1/Day 2, AUC(0-tlast) |
|
|
| 130 mg, Cycle 2/Day 2, AUC(0-tlast) |
|
|
| 130 mg, Cycle 1/Day 2, AUC(0-∞) |
|
|
| 130 mg, Cycle 2/Day 2, AUC(0-∞) |
|
|
| 185 mg, Cycle 1/Day 2, AUC(0-24) |
|
|
| 185 mg, Cycle 2/Day 2, AUC(0-24) |
|
|
| 185 mg, Cycle 1/Day 2, AUC(0-tlast) |
|
|
| 185 mg, Cycle 2/Day 2, AUC(0-tlast) |
|
|
| 185 mg, Cycle 1/Day 2, AUC(0-∞) |
|
|
| 185 mg, Cycle 2/Day 2, AUC(0-∞) |
|
|
| 240 mg, Cycle 1/Day 2, AUC(0-24) |
|
|
| 240 mg, Cycle 2/Day 2, AUC(0-24) |
|
|
| 240 mg, Cycle 1/Day 2, AUC(0-tlast) |
|
|
| 240 mg, Cycle 2/Day 2, AUC(0-tlast) |
|
|
| 240 mg, Cycle 1/Day 2, AUC(0-∞) |
|
|
| 240 mg, Cycle 2/Day 2, AUC(0-∞) |
|
|
| 275 mg, Cycle 1/Day 2, AUC(0-24) |
|
|
| 275 mg, Cycle 2/Day 2, AUC(0-24) |
|
|
| 275 mg, Cycle 1/Day 2, AUC(0-tlast) |
|
|
| 275 mg, Cycle 2/Day 2, AUC(0-tlast) |
|
|
| 275 mg, Cycle 1/Day 2, AUC(0-∞) |
|
|
| 275 mg, Cycle 2/Day 2, AUC(0-∞) |
|
|
| Title | Measurements |
|---|---|
|
| T-platinum from cisplatin, AUC (0-∞) |
|
|
| AUC (0-∞) |
|
|
| ASBI |
|
|
|
| 240 mg |
|
|
| 275 mg |
|
|
| Title | Measurements |
|---|---|
|
| Death within 30 days of last dose of study drug |
|
| Deaths during follow-up period |
|