Mirvetuximab Soravtansine and Gemcitabine Hydrochloride in Treating Patients With FRa-Positive Recurrent Ovarian, Primary Peritoneal, Fallopian Tube, Endometrial, or Triple Negative Breast Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02996825|
Recruitment Status : Recruiting
First Posted : December 19, 2016
Last Update Posted : October 16, 2019
|Condition or disease||Intervention/treatment||Phase|
|Estrogen Receptor Negative HER2/Neu Negative Progesterone Receptor Negative Recurrent Breast Carcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Recurrent Uterine Corpus Carcinoma Triple-Negative Breast Carcinoma Folate Receptor Alpha Positive||Drug: Gemcitabine Hydrochloride Other: Laboratory Biomarker Analysis Biological: Mirvetuximab Soravtansine Other: Pharmacological Study||Phase 1|
I. To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of gemcitabine hydrochloride (gemcitabine) when given in combination with mirvetuximab soravtansine (IMGN853) to patients with FRalpha-positive recurrent ovarian, primary peritoneal, fallopian tube, endometrial cancer, or triple negative breast cancer (TNBC).
I. To explore the toxicity, response rate (RR) and progression free survival (PFS) in three expanded cohorts of heavily pre-treated FRalpha-positive a) TNBC patients; b) endometrial cancer patients; and c) ovarian, primary peritoneal, or fallopian tube cancer patients, all treated at the initial recommended phase II dose.
II. To provide additional safety data from the expanded cohorts to help inform on the RP2D for each cohort.
III. To evaluate the relationship between intratumoral levels of DM4, tumoral expression of FRalpha, and plasma concentration of DM4 at 48 and 72 hours following the first dose.
IV. To determine the pharmacokinetics (PK) of DM4 and gemcitabine when given in combination.
I. To evaluate the role of archival FRalpha expression as a substitute for the 48-72 hour (H) expression in determining intratumoral concentration of DM4.
OUTLINE: This is a dose escalation study.
Patients receive mirvetuximab soravtansine intravenously (IV) on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 3 weeks in the absence of disease progression or unexpected toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 12 weeks thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||44 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Dose-Escalation Safety and Tolerability Study of Mirvetuximab Soravtansine (IMGN853) and Gemcitabine in Patients With FRa-positive Recurrent Ovarian, Primary Peritoneal, Fallopian Tube, Endometrial Cancer, or Triple Negative Breast Cancer (TNBC)|
|Actual Study Start Date :||October 2, 2017|
|Estimated Primary Completion Date :||September 2020|
|Estimated Study Completion Date :||September 2020|
Experimental: Treatment (IMGN853, gemcitabine hydrochloride)
Patients receive mirvetuximab soravtansine IV on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 3 weeks in the absence of disease progression or unexpected toxicity.
Drug: Gemcitabine Hydrochloride
Other: Laboratory Biomarker Analysis
Biological: Mirvetuximab Soravtansine
Other: Pharmacological Study
- Recommended phase II dose assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4 [ Time Frame: Up to 3 weeks ]Tables will be created to summarize toxicities by dose level, cycles delivered, and total dose delivered, and side effects by dose and by cycle.
- Assessment of biological correlatives assessed by biopsy [ Time Frame: Up to 2 years ]
- Incidence of treatment-emergent adverse events and clinically significant >= grade 3 changes assessed by CTCAE 4.0 [ Time Frame: Up to 2 years ]Will assess the type, severity and attribution, time to onset, and duration.
- PFS [ Time Frame: Time from study entry to disease progression, assessed up to 2 years ]
- Response assessed by Response Evaluation Criteria in Solid Tumors 1.1 [ Time Frame: Up to 2 years ]
- FRalpha expression [ Time Frame: Day 1 ]FRalpha expression at baseline (in archival tissue) and in a single research biopsy (Cohort C only) at 48-72H will be correlated to intratumoral and circulating levels of DM4. Will develop a model incorporating both blood levels and FRalpha expression as predictors of DM4 intratumoral drug concentration.
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): NCT02996825
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Mihaela C. Cristea, MD 800-826-4673 firstname.lastname@example.org|
|Principal Investigator: Mihaela C. Cristea, MD|
|City of Hope Rancho Cucamonga||Recruiting|
|Rancho Cucamonga, California, United States, 91730|
|Contact: Valerie Estala 626-256-4673 ext 81699 email@example.com|
|Principal Investigator: Behnam Ebrahimi, MD|
|Principal Investigator:||Mihaela Cristea, MD||City of Hope Medical Center|