Carboplatin, Gemcitabine Hydrochloride, and Berzosertib in Treating Patients With Recurrent and Metastatic Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
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|ClinicalTrials.gov Identifier: NCT02627443|
Recruitment Status : Active, not recruiting
First Posted : December 11, 2015
Last Update Posted : June 30, 2022
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Fallopian Tube Carcinoma Metastatic Ovarian Carcinoma Metastatic Primary Peritoneal Carcinoma Ovarian Endometrioid Tumor Ovarian High Grade Serous Adenocarcinoma Platinum-Sensitive Ovarian Carcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Stage IV Fallopian Tube Cancer AJCC v6 and v7 Stage IV Ovarian Cancer AJCC v6 and v7 Stage IV Primary Peritoneal Cancer AJCC v7||Drug: Berzosertib Drug: Carboplatin Drug: Gemcitabine Hydrochloride Other: Laboratory Biomarker Analysis Other: Pharmacological Study||Phase 1|
I. Assess safety and tolerability of the combination therapy carboplatin, gemcitabine hydrochloride (gemcitabine), and berzosertib (M6620 [VX-970]) in adult women with platinum sensitive recurrent high grade serous or high grade endometrioid ovarian, primary peritoneal or fallopian tube cancer. (Phase I Dose Escalation/Safety Lead-in) II. Determine the dose of the triple therapy to be used in the dose expansion cohort of the study. (Phase I Dose Escalation/Safety Lead-in) III. Confirm the safety at the maximum tolerated dose (MTD) for the addition of M6620 (VX-970) to carboplatin and gemcitabine in first or second recurrence of platinum sensitive high grade serous or endometrioid ovarian, primary peritoneal or fallopian tube carcinoma. (Expansion Cohort)
I. To determine if the MTD for the combination of carboplatin, gemcitabine and M6620 (VX-970) improves the confirmed response rate in adult women with platinum sensitive recurrent high grade serous or high grade endometrioid ovarian, primary peritoneal or fallopian tube cancer.
II. To determine the impact of the MTD on overall survival (OS), duration of response, and progression-free survival (PFS).
INTEGRATED CORRELATIVE STUDY OBJECTIVES:
I. Collection of specimens for biomarker studies to provide preliminary proof of mechanism. Assess, in an exploratory fashion, whether the combination of gemcitabine and carboplatin activates the ATR/CHK1 pathway at achievable concentrations and also whether M6620 inhibits the activated pathway.
II. To determine whether increased deoxyribonucleic acid (DNA) damage as assessed by two different multiplex assays correlates with response to combination therapy with M6620 (VX-970).
III. To determine whether mutations in homologous recombination repair genes correlate with response to combination therapy with M6620 (VX-970).
IV. To ascertain modulation of ATR autophosphorylation and other pharmacodynamic readouts for ATR inhibition by M6620 (VX-970).
OUTLINE: This is a dose-escalation study of gemcitabine hydrochloride and berzosertib.
Patients receive carboplatin intravenously (IV) over 30 minutes on day 1, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and berzosertib IV over 60 minutes on days 2 and 9. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1 Dose Escalation and Expansion Cohort of Carboplatin and Gemcitabine With or Without M6620 (VX-970) in First or Second Recurrence Platinum-Sensitive Epithelial Ovarian, Peritoneal, and Fallopian Tube Cancer|
|Actual Study Start Date :||November 4, 2016|
|Estimated Primary Completion Date :||November 30, 2022|
|Estimated Study Completion Date :||November 30, 2022|
Experimental: Treatment (carboplatin, gemcitabine hydrochloride, VX-970)
Patients receive carboplatin IV over 30 minutes on day 1, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and berzosertib IV over 60 minutes on days 2 and 9. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Gemcitabine Hydrochloride
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Maximum tolerated dose (MTD) (phase I dose escalation) [ Time Frame: Up to 28 days ]The MTD in this study will be defined as the highest safely tolerated dose, up to a maximum of dose level 4, where at most 1 out of six patients experience a dose limiting toxicity (DLT) with the next higher dose having at least 2 DLTs in 3 or more patients. Will be reported descriptively.
- Incidence of adverse events [ Time Frame: Up to 3 years ]The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Confirmed response rate [ Time Frame: Up to 3 years ]Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
- Overall survival (OS) [ Time Frame: From study entry to death from any cause, assessed up to 3 years ]OS will be estimated using the Kaplan-Meier method.
- Duration of response [ Time Frame: From first documented date of confirmed response (complete response [CR] or partial response [PR]), to the date at which progression is first documented, up to 3 years ]The duration of confirmed responses will be assessed using the Kaplan-Meier method.
- Progression free survival (PFS) [ Time Frame: From registration to the first of either disease progression or death from any cause, up to 3 years ]Disease progression will be determined based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. PFS will be estimated using the Kaplan-Meier method.
- Changes in the frequency of marker inhibition [ Time Frame: Baseline to up to 3 years ]Semi-quantitative data will be used to compare the data between the treatment arms using boxplots and descriptive statistics.
- Correlation between deoxyribonucleic acid (DNA) damage markers and mutation data with clinical endpoints (i.e. response, PFS, OS) [ Time Frame: Up to 3 years ]Statistical and graphical techniques will be used to explore these relationships. For time-to-event endpoints, we will use Cox proportional hazards models, and for response data we will use Logistic regression models. In addition, we will use Fisher's exact tests to test the association between categorical marker data and response.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02627443
|United States, Arizona|
|Mayo Clinic Hospital in Arizona|
|Phoenix, Arizona, United States, 85054|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Colorado|
|University of Colorado Hospital|
|Aurora, Colorado, United States, 80045|
|United States, Florida|
|University of Florida Health Science Center - Gainesville|
|Gainesville, Florida, United States, 32610|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224-9980|
|United States, Kentucky|
|University of Kentucky/Markey Cancer Center|
|Lexington, Kentucky, United States, 40536|
|United States, Michigan|
|Wayne State University/Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|Weisberg Cancer Treatment Center|
|Farmington Hills, Michigan, United States, 48334|
|United States, Minnesota|
|Mayo Clinic in Rochester|
|Rochester, Minnesota, United States, 55905|
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08903|
|United States, Pennsylvania|
|Thomas Jefferson University Hospital|
|Philadelphia, Pennsylvania, United States, 19107|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, Virginia|
|University of Virginia Cancer Center|
|Charlottesville, Virginia, United States, 22908|
|Principal Investigator:||Andrea E Wahner Hendrickson||Mayo Clinic Cancer Center LAO|