Mirvetuximab Soravtansine and Gemcitabine Hydrochloride in Treating Patients With FRalpha-Positive Recurrent Ovarian, Primary Peritoneal, Fallopian Tube, Endometrial, or Triple Negative Breast Cancer

NCT02996825 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 16294NCI-2016-01913
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the side effects and best dose of mirvetuximab soravtansine and gemcitabine hydrochloride in treating patients with folate receptor (FR) alpha-positive ovarian, primary peritoneal, fallopian tube, endometrial, or triple negative breast cancer that has come back. Mirvetuximab soravtansine is a monoclonal antibody, called mirvetuximab, linked to a chemotherapy drug called DM4. Mirvetuximab attaches to FOLR1 positive cancer cells in a targeted way and delivers DM4 to kill them. Drugs used in the chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving mirvetuximab soravtansine and gemcitabine may work better in treating patients with FRalpha-positive ovarian, primary peritoneal, fallopian tube, endometrial, or triple negative breast cancer.

Conditions

Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Recommended phase II dose assessed by Common Terminology Criteria for Adverse Events version 4

  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 Outcomes (4)

• Incidence of treatment-emergent adverse events and clinically significant >= grade 3 changes assessed by Common Terminology Criteria for Adverse Events version 4.0

  Up to 2 years

• Response

  Up to 2 years

• Progression free survival

  Time from study entry to disease progression, assessed up to 2 years

• Assessment of biological correlatives assessed by biopsy

  Up to 2 years

Other Outcomes (1)

• FRalpha expression

  Day 1

Study Arms (1)

Treatment (IMGN853, gemcitabine hydrochloride)

EXPERIMENTAL

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.

Drug: Gemcitabine; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Biological: Mirvetuximab Soravtansine; Other: Pharmacological Study

Interventions

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Treatment (IMGN853, gemcitabine hydrochloride)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832, FF10832, Gemcitabine HCI, Gemzar, LY-188011, LY188011

Treatment (IMGN853, gemcitabine hydrochloride)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (IMGN853, gemcitabine hydrochloride)

Mirvetuximab Soravtansine BIOLOGICAL

Given IV

Also known as: IMGN853, M9346A-sulfo-SPDB-DM4

Treatment (IMGN853, gemcitabine hydrochloride)

Pharmacological Study OTHER

Correlative studies

Treatment (IMGN853, gemcitabine hydrochloride)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must have one of the following pathologically documented recurrent tumor types with FRalpha positivity by the Ventana immunohistochemistry (IHC):
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope Upland

Upland, California, 91786, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Fallopian Tube Neoplasms; Ovarian Neoplasms; Triple Negative Breast Neoplasms

Interventions

Gemcitabine; mirvetuximab soravtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Edward W Wang

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2016
• First Posted: December 19, 2016
• Study Start: March 22, 2017
• Primary Completion: February 9, 2024
• Study Completion: February 9, 2024
• Last Updated: April 2, 2024

Record last verified: 2024-03

Locations

US (2)