Mirvetuximab Soravtansine and Rucaparib Camsylate in Treating Participants With Recurrent Endometrial, Ovarian, Fallopian Tube or Primary Peritoneal Cancer

NCT03552471 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-18007NCI-2018-00438
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of mirvetuximab soravtansine and rucaparib camsylate in treating participants with endometrial, ovarian, fallopian tube or primary peritoneal cancer that has come back. Drugs such as mirvetuximab soravtansine are antibodies linked to a toxic substance and may help find certain tumor cells and kill them without harming normal cells. Rucaparib camsylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving mirvetuximab soravtansine and rucaparib camsylate may work better in treating participants with recurrent endometrial, ovarian, fallopian tube or primary peritoneal cancer.

Conditions

BRCA1 Gene Mutation; BRCA2 Gene Mutation; Folate Receptor Alpha Positive; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Uterine Serous Carcinoma; Recurrent Uterine Carcinosarcoma; Platinum Resistant Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Recommended phase II dose (RPTD) of mirvetuximab soravtansine and rucaparib camsylate in combination

  based on DLT and toxicity

  At the end of Cycle 1 (each cycle 15 days)

Secondary Outcomes (3)

• Incidence of adverse effects graded according to CTCAE v. 4.0

  while on study drug and up to 30 days after (through study treatment completion, an average of 1 year)

• Objective anti-tumor activity (complete and partial response) of mirvetuximab soravtansine and rucaparib in combination

  Up to 1 year after completion of study treatment

• Progression-free survival

  From start of treatment up to 1 year after completion of study treatment

Other Outcomes (1)

• Pharmacokinetics of mirvetuximab soravtansine and rucaparib in combination Cmax trough concentrations

  predose and post dose at selected times

Study Arms (1)

Treatment (mirvetuximab soravtansine, rucaparib)

EXPERIMENTAL

Participants receive mirvetuximab soravtansine IV on day 1 and rucaparib PO BID on days 1 through 21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Mirvetuximab Soravtansine; Other: Pharmacokinetic Study; Drug: Rucaparib Camsylate

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (mirvetuximab soravtansine, rucaparib)

Mirvetuximab Soravtansine BIOLOGICAL

Given IV

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

Treatment (mirvetuximab soravtansine, rucaparib)

Pharmacokinetic Study OTHER

Correlative studies

Also known as: PHARMACOKINETIC, PK Study

Treatment (mirvetuximab soravtansine, rucaparib)

Rucaparib Camsylate DRUG

Given PO

Also known as: 8-Fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one ((1S,4R)-7,7dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonic Acid Salt, C0-338, Rubraca, Rucaparib Phosphate

Treatment (mirvetuximab soravtansine, rucaparib)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed:
• Recurrent endometrial cancer (all histologies, including carcinosarcoma)
• Recurrent ovarian, primary peritoneal (female only), or fallopian tube cancer
• all histologies except low grade serous or clear cell carcinoma unless the patient has a known somatic or germline breast cancer (BRCA) mutation disease that is metastatic and for which standard curative measures do not exist or are no longer effective
• For the dose escalation portion of the trial, patients with available therapies known to confer clinical benefit (platinum sensitive ovarian cancer) must be excluded
• For the dose expansion cohort, patients with recurrent endometrial cancer, recurrent BRCA mutated ovarian cancer (except first-recurrence platinum sensitive ovarian cancer), and platinum resistant ovarian cancer are eligible
• Patients must have confirmation of folate receptor-a (FR-alpha) positivity by immunohistochemistry (IHC) (? 25% of tumor staining at ? 2 + intensity) on archival tissue or recent biopsy.
• Patients must be willing and able to undergo tissue biopsy for research
• If tumor tissue obtained from the biopsy is deemed inadequate, and the patient is unwilling or unable to have another biopsy, the patient may be considered for enrollment if archival tumor tissue is provided and deemed of adequate quality; this must occur prior to any treatment with rucaparib or mirvetuximab soravtansine
• If biopsy is deemed unsafe to attempt or to perform, and if archival tumor tissue is available and deemed of adequate quality, the patient may enroll on trial
• Biopsy must be of solid tumor tissue; ascites is not acceptable
• Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
• Prior therapy:
• Patients may have received unlimited prior treatment for the dose escalation part
• For the expansion cohort patients must have ? 4 prior lines of chemotherapy

You may not qualify if:

• Patients with available therapies known to confer clinical benefit (platinum sensitive recurrent ovarian cancer) must be excluded from the dose escalation portion
• For the dose expansion cohort patients with first-recurrence platinum-sensitive ovarian cancer must be excluded
• Patients who have had chemotherapy or radiotherapy within 4 weeks or five half-lives whichever is shorter (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual drug related toxicities \> grade 1) except for alopecia and grade 2 fatigue
• Patients who are receiving any other investigational agents
• Primary platinum refractory disease (disease progression on first platinum treatment or recurrence within 3 months of completing first platinum regimen)
• Patients with clear cell or low grade ovarian cancer unless the patient has a known germline or somatic breast cancer (BRCA) mutation or a mutation in another homologous recombination gene
• Any known gastrointestinal disorder determined by the investigator that interferes with the absorption of rucaparib
• Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids; patients with treated brain metastases are eligible as long as they completed prior brain radiation therapy more than 14 days prior to first dose of study therapy, are not experiencing seizures and are not receiving steroids for symptomatic brain metastases (for at least 7 days prior to first dose of study treatment)
• History of leptomeningeal carcinomatosis
• Subjects with a known history of uncontrolled seizures
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to rucaparib, mirvetuximab soravtansine or monoclonal antibodies
• Uncontrolled inter-current illness including, but not limited to:
• Ongoing or active infection (requiring IV antibiotics within 2 weeks of study enrollment)
• Symptomatic/uncontrolled congestive heart failure (New York heart association \> class II)

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• ImmunoGen, Inc.: collaborator
• Clovis Oncology, Inc.: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

mirvetuximab soravtansine; Pharmacogenomic Variants; rucaparib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; 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)

Polymorphism, Genetic; Genetic Variation; Genetic Phenomena

Study Officials

• Floor Backes, MD

  Ohio State University Comprehensive Cancer 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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 26, 2018
• First Posted: June 11, 2018
• Study Start: July 12, 2018
• Primary Completion: June 24, 2022
• Study Completion: December 19, 2022
• Last Updated: February 13, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)