- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02996825
Mirvetuximab Soravtansine and Gemcitabine Hydrochloride in Treating Patients With FRalpha-Positive Recurrent Ovarian, Primary Peritoneal, Fallopian Tube, Endometrial, or Triple Negative Breast Cancer
A Phase I Dose-Escalation Safety and Tolerability Study of MirvetuximabSoravtansine (IMGN853) and Gemcitabine in Patients With FRa-positive Recurrent Ovarian, Primary Peritoneal, Fallopian Tube, Endometrial Cancer, or Triple Negative Breast Cancer (TNBC)
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVE:
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).
SECONDARY OBJECTIVES:
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.
EXPLORATORY OBJECTIVE:
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. Cycles repeat every 3 weeks in the absence of disease progression or unexpected toxicity.
After completion of study treatment, patients are follow up at 30 days and then every 12 weeks thereafter.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Duarte, California, United States, 91010
- City of Hope Medical Center
-
Upland, California, United States, 91786
- City of Hope Upland
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
All patients must have one of the following pathologically documented recurrent tumor types with FRalpha positivity by the Ventana immunohistochemistry (IHC):
- Ovarian, primary peritoneal, fallopian tube (with exclusion of low grade, clear cell or sarcomatoid histologies for ovarian cancer) >= 50% of tumor staining >= 2+ intensity
- Endometrial >= 50% of tumor staining >= 2+ intensity
- TNBC confirmed by medical history of HER2-negative (confirmed by IHC 0, 1+ regardless of fluorescence in situ hybridization [FISH] ratio; IHC 2+ with FISH ratio < 2.0 or HER2 gene copy < 6.0; FISH ratio of 0, indicating gene deletion; when positive and negative in situ hybridization controls are present); estrogen receptor (ER) negative (confirmed as ER expression =< 1% positive tumor nuclei); progesterone receptor (PR) negative (confirmed as PR expression =< 1% positive tumor nuclei): >= 25% of tumor staining >= 1+ intensity
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions >= 10 mm and short axis for nodal lesions >= 15 mm); patients with recurrent ovarian, primary peritoneal, fallopian tube cancer may have biochemical relapse only, with baseline values of CA-125 at least 2 X upper limit of normal (ULN)
- Treatment with targeted agents, immunotherapy, or hormones is allowed; patients are only eligible if they have received and failed, or have been intolerant to standard treatments known to confer clinical benefit
- Life expectancy of greater than 3 months
- Absolute neutrophil count >= 1.5 x 10^9/L, determined within 14 days of registration
- Platelets >= 100 x 10^9/L, determined within 14 days of registration
- Total bilirubin =< 1.5 x upper limit of normal (ULN), determined within 14 days of registration
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal, determined within 14 days of registration
- Alkaline phosphatase =< 2.5 X institutional upper limit of normal, determined within 14 days of registration
- Creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal, determined within 14 days of registration
- Women of childbearing potential must have a negative pregnancy test at screening and must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 3 months after the last dose of IMGN853 and gemcitabine
- Patients must consent to analysis on archival tissue
- Ability to understand and the willingness to sign a written informed consent document
- Patients must have resolution of toxic effect(s) of the most recent prior chemotherapy to grade 1 or less (except alopecia)
- Cohort A: Patients with TNBC must have received no more than 4 lines of systemic cytotoxic chemotherapy; patients must have received and failed, or have been intolerant to anthracycline, taxanes, capecitabine, eribulin or other agents known to confer clinical benefit; patients are not required to fail all these agents if, in the investigator's opinion, patients would benefit from treatment on current protocol
- Cohort B: Patients with recurrent endometrial cancer may have received up to 2 lines of cytotoxic chemotherapy (adjuvant and one line for recurrent disease, or 2 lines of chemotherapy for recurrent uterine cancer in patients who did not receive adjuvant chemotherapy); patients must have received and failed, or have been intolerant to platinum agents, taxanes, liposomal doxorubicin or other agents known to confer clinical benefit; patients are not required to fail all these agents if, in the investigator's opinion, patients would benefit from treatment on current protocol
- Cohort C: Eligible patients must have received no more than 4 lines of systemic cytotoxic chemotherapy and must have disease resistant to platinum therapy (disease that progressed during or within six months of completing subsequent platinum therapy); primary platinum refractory patients are eligible providing they meet other eligibility criteria; in addition to platinum agents, patients must have received and failed, or have been intolerant to taxanes, liposomal doxorubicin or other agents known to confer clinical benefit; patients are not required to fail all these agents if, in the investigator's opinion, patients would benefit from treatment on current protocol
- Cohort C: Patients in this cohort only will require a single tumor biopsy 48-72H after the first administration of IMGN853 and gemcitabine on day 1, cycle 1 of treatment, providing it is safe/feasible and confers non-significant risk to patient
Exclusion Criteria:
- Previous treatment with gemcitabine
- Prior treatment with FR-targeting investigational agents is not allowed
- Patients who have had chemotherapy (including investigational cytotoxic chemotherapy), biologic agents (e.g., cytokines or antibodies) within 3 weeks (6 weeks for nitrosoureas or mitomycin C) before the first dose of study treatment
- Patients who have received radiation within 14 days before the first dose of study treatment
- Any other prior malignancy from which the patient has been disease free for less than 3 years, with the exception of adequately treated and basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site
- Patients with known brain metastases
Serious concurrent illness or clinically-relevant active infection, including, but not limited to the following:
- Known active hepatitis B or C
- Known human immunodeficiency virus (HIV) infection
- Varicella-zoster virus (shingles)
- Cytomegalovirus infection
- Any other known concurrent infectious disease, requiring IV antibiotics with 2 weeks of study enrollment
- Other intercurrent illness including, but not limited to symptomatic congestive heart failure and/or QT interval > 470 for females and > 450 for males, unstable angina pectoris, cardiac arrhythmia, hemorrhagic or ischemic stroke within the last 6 months or psychiatric illness/social situations that would limit compliance with study requirements
- History of interstitial pneumonitis
- History of cirrhotic liver disease
- Presence of > grade 1 peripheral neuropathy
- Active or chronic corneal disorder, including but not limited to the following: Sjogren's syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring on-going treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision
- Major surgery within 2 months prior to enrollment or minor surgery within 7 days of the first day of treatment
- History or evidence of thrombotic or hemorrhagic disorders within 6 months before first study treatment
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or IMGN853
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with gemcitabine or IMGN853
- Required used of folate-containing supplements (e.g. folate deficiency)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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. Cycles repeat every 3 weeks in the absence of disease progression or unexpected toxicity.
|
Correlative studies
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Recommended phase II dose assessed by Common Terminology Criteria for Adverse Events 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.
|
Up to 3 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of treatment-emergent adverse events and clinically significant >= grade 3 changes assessed by Common Terminology Criteria for Adverse Events version 4.0
Time Frame: Up to 2 years
|
Will assess the type, severity and attribution, time to onset, and duration.
|
Up to 2 years
|
Response
Time Frame: Up to 2 years
|
Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1.
|
Up to 2 years
|
Progression free survival
Time Frame: Time from study entry to disease progression, assessed up to 2 years
|
Time from study entry to disease progression, assessed up to 2 years
|
|
Assessment of biological correlatives assessed by biopsy
Time Frame: Up to 2 years
|
Up to 2 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Day 1
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Edward W Wang, City of Hope Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Skin Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Breast Diseases
- Breast Neoplasms
- Carcinoma
- Recurrence
- Triple Negative Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Immunoconjugates
- Maytansine
- Gemcitabine
- Mirvetuximab soravtansine
Other Study ID Numbers
- 16294 (Other Identifier: City of Hope Medical Center)
- NCI-2016-01913 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Recurrent Fallopian Tube Carcinoma
-
National Cancer Institute (NCI)NRG OncologyActive, not recruitingOvarian Seromucinous Carcinoma | Recurrent Ovarian High Grade Serous Adenocarcinoma | Recurrent Platinum-Resistant Ovarian Carcinoma | Fallopian Tube Mucinous Adenocarcinoma | Recurrent Fallopian Tube Clear Cell Adenocarcinoma | Recurrent Fallopian Tube Endometrioid Adenocarcinoma | Recurrent... and other conditionsUnited States, Puerto Rico
-
National Cancer Institute (NCI)CompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal CarcinomaUnited States
-
Roswell Park Cancer InstituteCompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian Clear Cell Tumor | Fallopian Tube Endometrioid Tumor | Ovarian Endometrioid Tumor | Fallopian Tube Mucinous Neoplasm | Fallopian Tube Serous Neoplasm | Ovarian Serous Tumor | Ovarian Mucinous...United States
-
Mayo ClinicNational Cancer Institute (NCI)CompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal CarcinomaUnited States
-
Northwestern UniversityNational Cancer Institute (NCI); Ipsen BiopharmaceuticalsCompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Platinum-Resistant Ovarian Carcinoma | Refractory Ovarian Carcinoma | Refractory Fallopian Tube... and other conditionsUnited States
-
National Cancer Institute (NCI)NRG OncologyActive, not recruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian Seromucinous Carcinoma | Recurrent Platinum-Resistant Ovarian Carcinoma | Primary Peritoneal High Grade Serous Adenocarcinoma | Ovarian High Grade Serous Adenocarcinoma | Fallopian... and other conditionsUnited States, Puerto Rico
-
National Cancer Institute (NCI)CompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal CarcinomaUnited States
-
National Cancer Institute (NCI)NRG OncologyCompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian Clear Cell Adenocarcinoma | Fallopian Tube Clear Cell AdenocarcinomaUnited States
-
M.D. Anderson Cancer CenterAstraZeneca; Aravive Biologics IncActive, not recruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Platinum-Resistant Ovarian Carcinoma | Refractory Ovarian Carcinoma | Refractory Fallopian Tube... and other conditionsUnited States
-
Roswell Park Cancer InstituteActive, not recruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Platinum-Resistant Ovarian Carcinoma | Platinum-Sensitive Ovarian Carcinoma | Refractory Ovarian... and other conditionsUnited States
Clinical Trials on Laboratory Biomarker Analysis
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
National Cancer Institute (NCI)Recruiting
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingLynch Syndrome | Recurrent Uterine Corpus Carcinoma | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingRecurrent Uterine Corpus Carcinoma | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)RecruitingStage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian CancerUnited States
-
Ohio State University Comprehensive Cancer CenterActive, not recruitingLung Cancer | Radiation Toxicity | Adult Brain TumorUnited States
-
National Cancer Institute (NCI)Active, not recruitingMalignant NeoplasmUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Askin TumorUnited States, Canada, Puerto Rico, Australia, New Zealand, Switzerland
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Osteosarcoma | Metastatic Osteosarcoma | Localized OsteosarcomaUnited States