| ID | Type | Description | Link |
|---|---|---|---|
| HUM00079048 | Other Identifier | University of Michigan |
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The investigators' long-term goal is to improve the survival of patients with pancreatic cancer by enhancing the efficacy of gemcitabine-radiation by adding the Wee1 inhibitor MK-1775.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MK-1775/ Gemcitabine/ Radiation Therapy | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-1775 | Drug | MK-1775 will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) of AZD1775 (MK-1775) When Used Concurrently With Gemcitabine and Radiation Therapy. | Probability of dose limiting toxicities was calculated for each dose (p[DLT/d]) using the Time to Event Continual Reassessment Method (TITE-CRM). The target DLT rate was 0.30. Dose level 1 (150 mg AZD1775) was determined to be the MTD and recommended phase 2 dose (RP2D). | The observation period for MTD is defined as the first 4 cycles of treatment (with a 3 week break between cycle 3 and cycle 4), for a total of 105 days in length. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Phosphorylation Inhibition of Greater Than 0 | During the first cycle of treatment, patients underwent 2 biopsies: 3 h after treatment with gemcitabine (but before MK- 1775), and 2 hours after MK-1775. WEE1 signaling was assessed using immunohistochemistry (IHC) to measure phosphorylation of various markers including Cdk1 (Y15). Inhibition was quantified as the within subject change in the above markers between the two biopsy timepoints. Descriptive statistics of inhibition across subjects (for each marker) were calculated and reported by dose level. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Theodore Lawrence, M.D., Ph.D. | University of Michigan Rogel Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan Hospital | Ann Arbor | Michigan | 48109 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31398082 | Derived | Cuneo KC, Morgan MA, Sahai V, Schipper MJ, Parsels LA, Parsels JD, Devasia T, Al-Hawaray M, Cho CS, Nathan H, Maybaum J, Zalupski MM, Lawrence TS. Dose Escalation Trial of the Wee1 Inhibitor Adavosertib (AZD1775) in Combination With Gemcitabine and Radiation for Patients With Locally Advanced Pancreatic Cancer. J Clin Oncol. 2019 Oct 10;37(29):2643-2650. doi: 10.1200/JCO.19.00730. Epub 2019 Aug 9. |
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| ID | Title | Description |
|---|---|---|
| FG000 | AZD-1775 100 mg | AZD-1775 (MK-1775) 100 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3 |
| FG001 | AZD-1775 125 mg | AZD-1775 (MK-1775) 125 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3 |
| FG002 | AZD-1775 150 mg | AZD-1775 (MK-1775) 150 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3 |
| FG003 | AZD-1775 175 mg | AZD-1775 (MK-1775) 175 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | AZD-1775 100 mg | AZD-1775 (MK-1775) 100 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Maximum Tolerated Dose (MTD) of AZD1775 (MK-1775) When Used Concurrently With Gemcitabine and Radiation Therapy. | Probability of dose limiting toxicities was calculated for each dose (p[DLT/d]) using the Time to Event Continual Reassessment Method (TITE-CRM). The target DLT rate was 0.30. Dose level 1 (150 mg AZD1775) was determined to be the MTD and recommended phase 2 dose (RP2D). | All participants who received at least one dose of the study drug were evaluable for MTD. | Posted | Number | mg | The observation period for MTD is defined as the first 4 cycles of treatment (with a 3 week break between cycle 3 and cycle 4), for a total of 105 days in length. |
|
Adverse events were collected during the course of treatment (26 weeks). The time frame for data collection for all-cause mortality varied depending on the length of patient follow-up, which ranged from 1.8 months to 47.2 months. All-cause mortality includes all observed deaths while the study was ongoing, regardless of duration of patient follow-up. Patients who enrolled soon after the study opened may have been followed longer than patients who enrolled later, toward the end of the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AZD-1775 100 mg | AZD-1775 (MK-1775) 100 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pruritic Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Theodore Lawrence, M.D., Ph.D. | University of Michigan Rogel Cancer Center | 734-647-9955 | tsl@umich.edu |
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| 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 | Apr 7, 2017 | Oct 10, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| C549567 | adavosertib |
| D000093542 | Gemcitabine |
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
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| Gemcitabine | Drug | Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. |
|
| Radiation Therapy | Radiation | 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. |
|
| First cycle of treatment |
| Overall Survival | Overall survival (OS) summarized by Kaplan-Meier curves and characterized by descriptive statistics such as median OS. The time frame for data collection for OS varied depending on the length of patient follow-up, which ranged from 1.8 months to 47.2 months. Patients who enrolled soon after the study opened may have been followed longer than patients who enrolled later, toward the end of the study. | Up to 48 months following treatment |
| Time From Date of Registration to Date of Documented Disease Progression | Time from date of registration to date of documented disease progression summarized by Kaplan-Meier method. The time frame for data collection varied depending on the length of patient follow-up, which ranged from 1.8 months to 47.2 months. Patients who enrolled soon after the study opened may have been followed longer than patients who enrolled later, toward the end of the study. | Up to 48 months following treatment |
| BG001 | AZD-1775 125 mg | AZD-1775 (MK-1775) 125 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3 |
| BG002 | AZD-1775 150 mg | AZD-1775 (MK-1775) 150 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3 |
| BG003 | AZD-1775 175 mg | AZD-1775 (MK-1775) 175 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3 |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
| Secondary | Number of Patients With Phosphorylation Inhibition of Greater Than 0 | During the first cycle of treatment, patients underwent 2 biopsies: 3 h after treatment with gemcitabine (but before MK- 1775), and 2 hours after MK-1775. WEE1 signaling was assessed using immunohistochemistry (IHC) to measure phosphorylation of various markers including Cdk1 (Y15). Inhibition was quantified as the within subject change in the above markers between the two biopsy timepoints. Descriptive statistics of inhibition across subjects (for each marker) were calculated and reported by dose level. | 20 participants were evaluable for this outcome measure. Two sequential skin punch biopsies were obtained from 20 of the 34 study participants. | Posted | Number | participants | First cycle of treatment |
|
|
|
| Secondary | Overall Survival | Overall survival (OS) summarized by Kaplan-Meier curves and characterized by descriptive statistics such as median OS. The time frame for data collection for OS varied depending on the length of patient follow-up, which ranged from 1.8 months to 47.2 months. Patients who enrolled soon after the study opened may have been followed longer than patients who enrolled later, toward the end of the study. | Posted | Median | 90% Confidence Interval | months | Up to 48 months following treatment |
|
|
|
| Secondary | Time From Date of Registration to Date of Documented Disease Progression | Time from date of registration to date of documented disease progression summarized by Kaplan-Meier method. The time frame for data collection varied depending on the length of patient follow-up, which ranged from 1.8 months to 47.2 months. Patients who enrolled soon after the study opened may have been followed longer than patients who enrolled later, toward the end of the study. | Posted | Median | 90% Confidence Interval | months | Up to 48 months following treatment |
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| 1 |
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| 1 |
| 1 |
| 0 |
| 1 |
| EG001 | AZD-1775 125 mg | AZD-1775 (MK-1775) 125 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3 | 9 | 13 | 5 | 13 | 3 | 13 |
| EG002 | AZD-1775 150 mg | AZD-1775 (MK-1775) 150 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3 | 5 | 9 | 4 | 9 | 3 | 9 |
| EG003 | AZD-1775 175 mg | AZD-1775 (MK-1775) 175 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3 | 6 | 11 | 8 | 11 | 4 | 11 |
| ALT/AST elevation | Gastrointestinal disorders | Systematic Assessment |
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| Anorexia, nausea/vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Cholangitis | Gastrointestinal disorders | Systematic Assessment |
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| Colitis | Gastrointestinal disorders | Systematic Assessment |
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| Diverticulitis | Gastrointestinal disorders | Systematic Assessment |
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| GI bleed | Gastrointestinal disorders | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | Systematic Assessment |
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| Febrile Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Septic shock | Blood and lymphatic system disorders | Systematic Assessment |
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| Pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Pulmonary embolus | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Fever | General disorders | Systematic Assessment |
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| Altered mental status | General disorders | Systematic Assessment |
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| Fever | General disorders | Systematic Assessment |
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| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
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| Edema | General disorders | Systematic Assessment |
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| D011743 |
| Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D013812 | Therapeutics |