Niraparib and Copanlisib in Treating Patients With Recurrent Endometrial, Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
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|ClinicalTrials.gov Identifier: NCT03586661|
Recruitment Status : Recruiting
First Posted : July 13, 2018
Last Update Posted : July 21, 2020
|Condition or disease||Intervention/treatment||Phase|
|Deleterious BRCA1 Gene Mutation Deleterious BRCA2 Gene Mutation Endometrial Adenocarcinoma High Grade Ovarian Serous Adenocarcinoma Platinum-Resistant Ovarian Carcinoma Primary Peritoneal High Grade Serous Adenocarcinoma Progressive Disease Recurrent Endometrial Carcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma||Drug: Copanlisib Drug: Niraparib||Phase 1|
I. To determine the maximally tolerated dose (MTD) and recommended phase II dose (RP2D) of the combination of niraparib and copanlisib in patients with recurrent high-grade serous or BRCA mutant ovarian cancer or recurrent endometrial, fallopian tube, or primary peritoneal cancer.
I. To determine the tolerability of the RP2D of niraparib and copanlisib. II. To determine the safety and observed toxicities of the combination of niraparib and copanlisib in patients with recurrent endometrial, recurrent high-grade serous ovarian, or BRCA mutant ovarian cancer.
III. To estimate the activity of the drug combination at all dose levels in each patient cohort by objective response rate and proportion of patients surviving progression free (PFS) at 6 months.
IV. To determine response duration of the drug combination at all dose levels. V. To determine the pharmacokinetics (PK) of the combination to assess the presence of any drug interaction between the two co-administered agents.
I. To determine if response to therapy is associated with molecular profile of the tumor (including, but not limited to, molecular aberrations in the PI3K-AKT-mTOR pathway or defects in homologous recombination) before treatment.
II. To examine associations with early changes in functional proteomic biomarkers in tumor biopsies before and after treatment and tumor response in patients with recurrent endometrial, recurrent high-grade serous ovarian, or BRCA mutant ovarian cancer treated with the investigational agents.
OUTLINE: This is a dose-escalation study.
Patients receive niraparib orally (PO) daily on days 1-28 and copanlisib intravenously (IV) over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 and 90 days, then every 3 months for up to 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||44 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib Study of the Oral PARP Inhibitor Niraparib With the Intravenous PI3K Inhibitor Copanlisib for Recurrent Endometrial and Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer|
|Actual Study Start Date :||April 29, 2019|
|Estimated Primary Completion Date :||April 30, 2021|
|Estimated Study Completion Date :||April 30, 2022|
Experimental: Treatment (niraparib, copanlisib)
Patients receive niraparib PO daily on days 1-28 and copanlisib IV on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Maximum tolerated dose [ Time Frame: Up to 4 weeks ]Defined as the highest dose for which the posterior probability of toxicity is closest to 30%. Will employ the Bayesian optimal interval design. We will report the posterior probability of dose limiting toxicities (DLT) for each dose level and a 90% credible interval for the probability of DLT at each dose level.
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): NCT03586661
|Contact: Shannon Westinfirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Shannon N. Westin 713-794-4314|
|Principal Investigator: Shannon N. Westin|
|Principal Investigator:||Shannon N Westin||M.D. Anderson Cancer Center|