Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
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ClinicalTrials.gov Identifier: NCT02101775 |
Recruitment Status :
Active, not recruiting
First Posted : April 2, 2014
Results First Posted : September 8, 2023
Last Update Posted : March 8, 2024
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Tracking Information | ||||
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First Submitted Date ICMJE | March 28, 2014 | |||
First Posted Date ICMJE | April 2, 2014 | |||
Results First Submitted Date ICMJE | March 21, 2023 | |||
Results First Posted Date ICMJE | September 8, 2023 | |||
Last Update Posted Date | March 8, 2024 | |||
Actual Study Start Date ICMJE | July 21, 2014 | |||
Actual Primary Completion Date | February 3, 2022 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
Progression Free Survival [ Time Frame: From start of treatment until date of progression or death, whichever occurs first, up to 1 year follow-up ] To evaluate the progression free survival (PFS) of subjects with recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer receiving gemcitabine in combination with AZD1775 compared to subjects receiving gemcitabine in combination with placebo. Progression is defined, using the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guideline, as at least a 20% increase in the sum of the diameters of target lesions or the appearance of one or more new lesions.
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Original Primary Outcome Measures ICMJE |
PFS evaluated using RECIST version 1.1 [ Time Frame: Time from start of treatment to time to progression or death, whichever occurs first, assessed up to 1 year ] | |||
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Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures |
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Descriptive Information | ||||
Brief Title ICMJE | Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer | |||
Official Title ICMJE | A Randomized Placebo-Controlled Phase II Trial Comparing Gemcitabine Monotherapy to Gemcitabine in Combination With AZD 1775 (MK 1775) in Women With Recurrent, Platinum Resistant Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers | |||
Brief Summary | This randomized phase II clinical trial studies how well gemcitabine hydrochloride and WEE1 inhibitor MK-1775 work compared to gemcitabine hydrochloride alone in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of time. Gemcitabine hydrochloride may prevent tumor cells from multiplying by damaging their deoxyribonucleic acid (DNA, molecules that contain instructions for the proper development and functioning of cells), which in turn stops the tumor from growing. The protein WEE1 may help to repair the damaged tumor cells, so the tumor continues to grow. WEE1 inhibitor MK-1775 may block the WEE1 protein activity and may increase the effectiveness of gemcitabine hydrochloride by preventing the WEE1 protein from repairing damaged tumor cells without causing harm to normal cells. It is not yet known whether gemcitabine hydrochloride with or without WEE1 inhibitor MK-1775 may be an effective treatment for recurrent ovarian, primary peritoneal, or fallopian tube cancer. | |||
Detailed Description | PRIMARY OBJECTIVES: I. To evaluate the progression free survival (PFS) of subjects with recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer receiving gemcitabine (gemcitabine hydrochloride) in combination with AZD 1775 (MK-1775 [WEE1 inhibitor MK-1775]) compared to subjects receiving gemcitabine in combination with placebo. SECONDARY OBJECTIVES: I. To evaluate the objective response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of patients receiving gemcitabine combined with AZD 1775 (MK-1775) compared to patients receiving gemcitabine in combination with placebo. II. To evaluate the Gynecologic Cancer Intergroup (GCIG) cancer antigen (CA)125 response rate of patients receiving gemcitabine combined with AZD 1775 (MK-1775) compared to patients receiving gemcitabine in combination with placebo. III. To evaluate the overall survival of patients (max 1-year [yr] follow-up) receiving gemcitabine combined with AZD 1775 (MK-1775) compared to patients receiving gemcitabine in combination with placebo. IV. To evaluate the safety and tolerability of the combination of gemcitabine combined with AZD 1775 (MK-1775) in patients with recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer. V. To evaluate tumor protein p53 (TP53) mutations (presence of mutation and type of mutation) as potential predictive factors of benefit (defined as response or progression-free survival [PFS] prolongation) to AZD 1775 (MK-1775) and gemcitabine treatment. VI. To evaluate p53 protein expression by immunohistochemistry as potential predictive factors of benefit (defined as response or PFS prolongation) to AZD 1775 (MK-1775) and gemcitabine treatment. TERTIARY OBJECTIVES: I. To evaluate patient reported outcomes using Patient-Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE). II. To evaluate the concordance of TP53 mutations in the tumor specimen and TP53 mutations determined by tagged-amplicon deep sequencing (Tam-Seq) in circulating tumor DNA. III. To correlate the levels circulating DNA TP53 mutations by Tam-Seq with response. IV. Validation of phosphorylated-cyclin-dependent cycle 2 (pCDC2) and gamma-H2A histone family, member X (H2AX) in skin and tumor tissue as a pharmacodynamic marker of therapy. V. To correlate changes in pCDC2 and gamma-H2AX with survival outcomes and response rate. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive WEE1 inhibitor MK-1775 orally (PO) on days 1, 2, 8, 9, 15, and 16 and gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO on days 1, 2, 8, 9, 15, and 16 and gemcitabine hydrochloride as patients in Arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6-8 weeks (after the 30-37 day safety visit) for up to 1 year. |
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Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 2 | |||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single (Participant) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Lheureux S, Cristea MC, Bruce JP, Garg S, Cabanero M, Mantia-Smaldone G, Olawaiye AB, Ellard SL, Weberpals JI, Wahner Hendrickson AE, Fleming GF, Welch S, Dhani NC, Stockley T, Rath P, Karakasis K, Jones GN, Jenkins S, Rodriguez-Canales J, Tracy M, Tan Q, Bowering V, Udagani S, Wang L, Kunos CA, Chen E, Pugh TJ, Oza AM. Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2021 Jan 23;397(10271):281-292. doi: 10.1016/S0140-6736(20)32554-X. | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Active, not recruiting | |||
Actual Enrollment ICMJE |
124 | |||
Original Estimated Enrollment ICMJE |
90 | |||
Estimated Study Completion Date ICMJE | February 20, 2025 | |||
Actual Primary Completion Date | February 3, 2022 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | Canada, Singapore, United States | |||
Removed Location Countries | Australia | |||
Administrative Information | ||||
NCT Number ICMJE | NCT02101775 | |||
Other Study ID Numbers ICMJE | NCI-2014-00620 NCI-2014-00620 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) PHL-093 NCI 9568 9568 ( Other Identifier: University Health Network-Princess Margaret Hospital ) 9568 ( Other Identifier: CTEP ) N01CM00032 ( U.S. NIH Grant/Contract ) N01CM00038 ( U.S. NIH Grant/Contract ) N01CM00071 ( U.S. NIH Grant/Contract ) U10CA180821 ( U.S. NIH Grant/Contract ) UM1CA186644 ( U.S. NIH Grant/Contract ) UM1CA186705 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | No | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Current Responsible Party | National Cancer Institute (NCI) | |||
Original Responsible Party | Same as current | |||
Current Study Sponsor ICMJE | National Cancer Institute (NCI) | |||
Original Study Sponsor ICMJE | Same as current | |||
Collaborators ICMJE | Not Provided | |||
Investigators ICMJE |
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PRS Account | National Cancer Institute (NCI) | |||
Verification Date | March 2024 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |