Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Clovis Oncology, Inc. | INDUSTRY |
Not provided
Not provided
Not provided
The purpose of this study is to evaluate survival and response rate of the combination rucaparib and nivolumab as maintenance therapy in platinum-sensitive small cell lung carcinoma.
Small cell lung cancer (SCLC) is one of the most aggressive malignancies with a 5-year survival rate of less than 7%. SCLC is characterized by rapid doubling time, high growth fraction and early development of widespread metastases. SCLC accounts for roughly 93% of all high-grade neuroendocrine carcinomas. The prognosis for SCLC is extremely poor with a median survival less than a year for extensive-stage disease. Therapeutic options have not advanced significantly in over two decades, with frontline treatment consisting of platinum doublet therapy for 3-6 cycles. While most patients show an initial favorable response to Carboplatin/cisplatin + etoposide, this response is usually short-lived. Most patients relapse with resistant disease between 3 to 6 months after completion of initial chemotherapy.
Based on preclinical data supporting the role of immune checkpoint and PARP (poly ADP ribose polymerase ) inhibitors in SCLC, combining nivolumab and rucaparib has the potential to prolong progression-free survival and overall survival. These two classes of drugs have non-overlapping toxicities. This novel combination has not been tried in a front-line maintenance setting for SCLC.
Eligible patients will have pathological (biopsy) or cytologically confirmed stage IV SCLC, and have achieved either partial or complete response post frontline chemotherapy with platinum doublet. Patients will be treated with combination rucaparib and nivolumab. The recommended starting dose of rucaparib as a continuously administered oral monotherapy is 600 mg BID. Nivolumab will be administered as an intravenous infusion once every 4 weeks at a fixed dose of 480 mg. In the absence of treatment delays due to adverse event(s), treatment may continue for 24 months.
Progression-free survival, overall survival, disease control rates, objective response rate, quality of life, and tumor mutation burden will be evaluated during this study (up to 2 years).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with Stage IV SCLC | Experimental | Patients with extensive stage (IV) SCLC (small cell lung cancer) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rucaparib and Nivolumab | Combination Product | Rucaparib (600mg BID) and Nivolumab (480mg IV q4 wk) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival | Duration (time) of progression-free survival after response to initial platinum-based therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions from starting maintenance treatment | 0-2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Disease Control Rate | Disease control rate (DCR) is the number of patients who had either complete response (CR, Disappearance of all target lesions), partial response (PR, >=30% decrease in the sum of the longest diameter of target lesions) or stable disease (SD, less than 30% decrease in the sum of the biggest dimension but no more than 20% increase ) per RECICST 1.0 divided by the total number of patients. DOR= (CR+PR+SD)/Total number on trial x 100%. The timepoints were combined. The best responses were used in calculating disease control rate |
| Measure | Description | Time Frame |
|---|---|---|
| Tumor Mutation Burden | Correlate tumor mutation burden with treatment response. | 0-3 years |
| PD-L1 CPS | A combined positive score (CPS) for Programmed Death Ligand 1 (PD-L1) will be derived from immunohistochemical analysis of tumor tissue. |
Inclusion Criteria
Exclusion Criteria
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Zhonglin Hao, MD | University of Kentucky | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Markey Cancer Center, University of Kentucky | Lexington | Kentucky | 40536 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Patients With Stage IV SCLC | Patients with extensive stage (IV) SCLC (small cell lung cancer) Rucaparib and Nivolumab: Rucaparib (600mg BID) and Nivolumab (480mg IV q4 wk) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Patients With Stage IV SCLC | Patients with extensive stage (IV) SCLC (small cell lung cancer) Rucaparib and Nivolumab: Rucaparib (600mg BID) and Nivolumab (480mg IV q4 wk) |
| 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 | Progression Free Survival | Duration (time) of progression-free survival after response to initial platinum-based therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions from starting maintenance treatment | Posted | Median | 95% Confidence Interval | months | 0-2 years |
|
|
2 years
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 | Patients With Stage IV SCLC | Patients with extensive stage (IV) SCLC (small cell lung cancer) Rucaparib and Nivolumab: Rucaparib (600mg BID) and Nivolumab (480mg IV q4 wk) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Zhonglin Hao | University of Kentucky | 859-218-6704 | zhonglin.hao@uky.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 21, 2022 | Oct 19, 2023 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D055752 | Small Cell Lung Carcinoma |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| C531549 | rucaparib |
| D000077594 | Nivolumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 8 weeks, 16 weeks and 24 weeks post-treatment |
| Overall Survival | Percentage of surviving participants at 1 and 2 years | 0-2 years |
| Objective Response Rate | Objective response rate (ORR) is the proportion of patients with complete response or partial response according to RECIST v1.1. Patients with complete response at baseline will be excluded from ORR analysis. The timepoints were combined. The best responses were used in calculating objective response rate | 8 weeks, 16 weeks and 24 weeks post-treatment |
| Quality of Life Scale Baseline | Quality of life is assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaire, which probes function and symptoms. Scores range from 0-100. High scores on functional scales represent a high/healthy level of functioning; high scores symptom scales represent a high level of symptomology. | Baseline |
| Quality of Life Scale 4 Months | Quality of life is assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaire, which probes function and symptoms. Scores range from 0-100. High scores on functional scales represent a high/healthy level of functioning; high scores symptom scales represent a high level of symptomology. | 4 months |
| Quality of Life Scale at Disease Progression | Quality of life is assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaire, which probes function and symptoms. Scores range from 0-100. High scores on functional scales represent a high/healthy level of functioning; high scores symptom scales represent a high level of symptomology. | Disease Progression up to 2 years |
| 0-3 years |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Participants |
|
|
| Secondary | Disease Control Rate | Disease control rate (DCR) is the number of patients who had either complete response (CR, Disappearance of all target lesions), partial response (PR, >=30% decrease in the sum of the longest diameter of target lesions) or stable disease (SD, less than 30% decrease in the sum of the biggest dimension but no more than 20% increase ) per RECICST 1.0 divided by the total number of patients. DOR= (CR+PR+SD)/Total number on trial x 100%. The timepoints were combined. The best responses were used in calculating disease control rate | Posted | Number | percentage of participants | 8 weeks, 16 weeks and 24 weeks post-treatment |
|
|
|
| Secondary | Overall Survival | Percentage of surviving participants at 1 and 2 years | Posted | Number | percentage of participants | 0-2 years |
|
|
|
| Secondary | Objective Response Rate | Objective response rate (ORR) is the proportion of patients with complete response or partial response according to RECIST v1.1. Patients with complete response at baseline will be excluded from ORR analysis. The timepoints were combined. The best responses were used in calculating objective response rate | Posted | Count of Participants | Participants | 8 weeks, 16 weeks and 24 weeks post-treatment |
|
|
|
| Secondary | Quality of Life Scale Baseline | Quality of life is assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaire, which probes function and symptoms. Scores range from 0-100. High scores on functional scales represent a high/healthy level of functioning; high scores symptom scales represent a high level of symptomology. | 3 participants did not answer all questions | Posted | Mean | Standard Deviation | units on a scale | Baseline |
|
|
|
| Secondary | Quality of Life Scale 4 Months | Quality of life is assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaire, which probes function and symptoms. Scores range from 0-100. High scores on functional scales represent a high/healthy level of functioning; high scores symptom scales represent a high level of symptomology. | Only 10 participants completed the scale at the 4 month timepoint | Posted | Mean | Standard Deviation | units on a scale | 4 months |
|
|
|
| Secondary | Quality of Life Scale at Disease Progression | Quality of life is assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaire, which probes function and symptoms. Scores range from 0-100. High scores on functional scales represent a high/healthy level of functioning; high scores symptom scales represent a high level of symptomology. | Only 2 subjects have completed the questionnaire at progression. Due to this small sample size, the standard deviation can be 0 if the responses happen to be the same for questions related to "physical functioning" | Posted | Mean | Standard Deviation | units on a scale | Disease Progression up to 2 years |
|
|
|
| Other Pre-specified | Tumor Mutation Burden | Correlate tumor mutation burden with treatment response. | Not Posted | 0-3 years | Participants |
| Other Pre-specified | PD-L1 CPS | A combined positive score (CPS) for Programmed Death Ligand 1 (PD-L1) will be derived from immunohistochemical analysis of tumor tissue. | Not Posted | 0-3 years | Participants |
| 16 |
| 33 |
| 12 |
| 33 |
| 33 |
| 33 |
| Thrombotic thrombocytopenic purpura | Blood and lymphatic system disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | Systematic Assessment |
|
| Flu like symptoms | General disorders | Systematic Assessment |
|
| Enterocolitis infectious | Infections and infestations | Systematic Assessment |
|
| Lung infection | Infections and infestations | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | Systematic Assessment |
|
| White blood cell decreased | Investigations | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Encephalopathy | Nervous system disorders | Systematic Assessment |
|
| Seizure | Nervous system disorders | Systematic Assessment |
|
| Thrombotic thrombocytopenic purpura | Blood and lymphatic system disorders | Systematic Assessment |
|
| Blurred Vision | Eye disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Mucositis Oral | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
| Generalized Edema | General disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| Shingles | Infections and infestations | Systematic Assessment |
|
| Sinusitis | Infections and infestations | Systematic Assessment |
|
| Lung Infection | Infections and infestations | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | Systematic Assessment |
|
| Creatinine increased | Investigations | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | Systematic Assessment |
|
| Platelet count decreased | Investigations | Systematic Assessment |
|
| Thyroid stimulating hormone increased | Investigations | Systematic Assessment |
|
| Weight loss | Investigations | Systematic Assessment |
|
| White blood cell decreased | Investigations | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Other | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Sore Throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
|
| Emotional Functioning |
|
|
| Cognitive Functioning |
|
|
| Social Functioning |
|
|
| Global health status |
|
|
| Title | Measurements |
|---|---|
|
| Cognitive Functioning |
|
| Social Functioning |
|
| Global health status |
|
| Title | Measurements |
|---|---|
|
| Cognitive Functioning |
|
| Social Functioning |
|
| Global health status |
|