A Study Combining the M3814 Pill With Standard Chemotherapy in Patients With Ovarian Cancer With an Expansion in High Grade Serous Ovarian Cancer and Low Grade Serous Ovarian Cancer Patients
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|ClinicalTrials.gov Identifier: NCT04092270|
Recruitment Status : Recruiting
First Posted : September 17, 2019
Last Update Posted : May 5, 2020
|Condition or disease||Intervention/treatment||Phase|
|Fallopian Tube Clear Cell Adenocarcinoma Fallopian Tube Endometrioid Adenocarcinoma Fallopian Tube Mucinous Adenocarcinoma Fallopian Tube Transitional Cell Carcinoma Fallopian Tube Undifferentiated Carcinoma FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma FIGO Grade 3 Endometrial Endometrioid Adenocarcinoma High Grade Fallopian Tube Serous Adenocarcinoma High Grade Ovarian Serous Adenocarcinoma Ovarian Seromucinous Carcinoma Ovarian Undifferentiated Carcinoma Platinum-Sensitive Ovarian Carcinoma Primary Peritoneal High Grade Serous Adenocarcinoma Primary Peritoneal Transitional Cell Carcinoma Primary Peritoneal Undifferentiated Carcinoma Recurrent Fallopian Tube Carcinoma Recurrent Low Grade Fallopian Tube Serous Adenocarcinoma Recurrent Low Grade Ovarian Serous Adenocarcinoma Recurrent Ovarian Carcinoma Recurrent Ovarian Clear Cell Adenocarcinoma Recurrent Ovarian Endometrioid Adenocarcinoma Recurrent Ovarian Mucinous Adenocarcinoma Recurrent Ovarian Transitional Cell Carcinoma Recurrent Primary Peritoneal Carcinoma Recurrent Primary Peritoneal Low Grade Serous Adenocarcinoma||Drug: Nedisertib Drug: Pegylated Liposomal Doxorubicin Hydrochloride||Phase 1|
I. To determine the safety and tolerability of nedisertib (M3814) in combination with pegylated liposomal doxorubicin hydrochloride (PLD) and determine the recommended phase 2 dose (RP2D) of the combination in women with recurrent ovarian cancer.
I. To observe and record anti-tumor activity. II. To evaluate the pharmacokinetics of M3814 when given in combination with PLD.
I. To correlate response to treatment (as defined by response rate and progression free survival) with PLD exposure (in area under the curve [AUC]) and PLD associated toxicities in women with recurrent high grade serous and low grade serous ovarian cancer treated in the expansion cohorts.
OUTLINE: This is a dose-escalation study of nedisertib.
Patients receive nedisertib orally (PO) twice daily (BID) on days 1-28 and pegylated liposomal doxorubicin hydrochloride intravenously (IV) on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||46 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/Ib Dose Escalation Study of Pegylated Liposomal Doxorubicin (PLD) With M3814 in Ovarian Cancer With Planned Expansions in High Grade Serous (HGSOC) and Low Grade Serous Ovarian Cancer (LGSOC)|
|Actual Study Start Date :||February 24, 2020|
|Estimated Primary Completion Date :||September 1, 2022|
|Estimated Study Completion Date :||September 1, 2022|
Experimental: Treatment (nedisertib, PLD)
Patients receive nedisertib PO BID on days 1-28 and pegylated liposomal doxorubicin hydrochloride IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Pegylated Liposomal Doxorubicin Hydrochloride
- Incidence of adverse events [ Time Frame: Up to 1 year ]The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 will be utilized for adverse event reporting.
- Pharmacokinetics (PK) parameters of nedisertib [ Time Frame: Up to 1 year ]Individual PK parameters will be estimated for maximum of concentration, area under the curve, T1/2, apparent clearance/oral bioavailability, and apparent volume using non-compartmental methods. The PK variables will be tabulated and descriptive statistics (e.g., geometric means and coefficients of variation) calculated for each dose level. Pharmacokinetic parameters will be reported descriptively for exploratory comparison with historical data. Samples from the expansion phase may also be analyzed for M3814 for the purpose of population-PK analyses.
- Tumor response [ Time Frame: Within the first 10 months of treatment ]Tumor response will be defined according to Response Evaluation Criteria in Solid Tumors 1.1 and refers to the best overall response occurring.
- Duration of response [ Time Frame: From response documentation until progression of disease, assessed up to 1 year ]
- Progression-free survival [ Time Frame: From the beginning of the treatment until the progression date, death date, or the last radiological assessment without progressive disease, assessed up to 1 year ]Will be estimated using Kaplan-Meier method.
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): NCT04092270
|United States, Virginia|
|University of Virginia Cancer Center||Recruiting|
|Charlottesville, Virginia, United States, 22908|
|Contact: Site Public Contact 434-243-6303 PAS9E@virginia.edu|
|Principal Investigator: Linda R. Duska|
|Principal Investigator:||Rachel N Grisham||JHU Sidney Kimmel Comprehensive Cancer Center LAO|