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BRCA1 Gene MutationPhase 1NCT03552471

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

A Phase 1 study testing Laboratory Biomarker Analysis, Mirvetuximab Soravtansine and Pharmacokinetic Study in people with BRCA1 Gene Mutation and BRCA2 Gene Mutation, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Laboratory Biomarker Analysis, Mirvetuximab Soravtansine and Pharmacokinetic Study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
12 Jul 2018to 19 Dec 2022
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Hormonal therapy does not count towards total lines of therapy
  • Maintenance therapy is considered part of the preceding regimen if one or more of the same drugs are continued
  • Neoadjuvant and adjuvant chemotherapy are considered one regimen if they are a continuation of the same regimen with interval debulking surgery
  • Prior treatment with folate receptor (FR) targeting investigational agents is allowed for dose escalation provided that such treatment was not discontinued due to adverse events; prior FR-targeting investigational agents are not allowed for patients in the expansion cohort
  • Patients with recurrent endometrial, ovarian, fallopian tube or primary peritoneal cancer must have received at least one platinum-based chemotherapy regimen
  • Patients who have received prior taxanes, including weekly taxanes are allowed
  • Patients previously treated with a poly adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitor may be enrolled provided:
  • PARP inhibitor was not the most recent treatment
  • PARP inhibitor treatment was discontinued > 6 months before the first planned dose of rucaparib
  • Time from prior therapy:
  • Systemic anti-neoplastic therapy: five half-lives or four weeks, whichever is shorter (6 weeks for nitrosoureas or mitomycin C)
  • Hormonal therapy is not considered anti-neoplastic therapy
  • Radiotherapy: wide-field radiotherapy (e.g. > 30% of marrow-bearing bones) completed at least four weeks, or focal radiation completed at least two weeks, prior to starting study treatment
  • Eastern cooperative oncology group (ECOG) performance status ? 1 and life expectancy > 12 weeks
  • Leukocytes ? 2,000/mcL
  • Absolute neutrophil count ? 1,500/mcL
  • Platelets ? 100,000/mcL
  • Hemoglobin ? 9.0 g/dL
  • Total bilirubin ? 1.5 x upper limit of normal (ULN) (Patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN)
  • Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/ alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) ? 2.5 ? institutional upper limit of normal
  • Creatinine ? 1.5 x upper limit of normal (ULN) OR creatinine clearance ? 50 mL/min/1.73 m^2 (using Cockroft Gault Formula) for patients with creatinine levels above institutional normal
  • Corrected QT (QTc) interval ? 470 msec on screening electrocardiogram (ECG)
  • Major surgery must have been completed ? 4 weeks prior to starting treatment day 1; patient must be sufficiently recovered and stable from surgery prior to treatment day 1
  • Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; patients must have a negative pregnancy test (urine and/or serum) prior to enrollment
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • 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)
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  • 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)
  • Unstable angina pectoris
  • Recent myocardial infarction (< 6 months)
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled hypertension (? Common Terminology Criteria for Adverse Events [CTCAE] v4.03 grade 3)
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • Hemorrhagic or ischemic stroke < 6 months
  • Clinically-significant vascular disease (e.g. aortic aneurysm, or dissecting aneurysm), severe aortic stenosis clinically significant peripheral vascular disease, or ? grade 3 cardiac toxicity following prior chemotherapy
  • Interstitial lung disease (ILD)
  • Active peptic ulcer disease or gastritis interfering with the absorption of rucaparib
  • Active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C
  • Active varicella zoster infection, cytomegalovirus infection, or history of tuberculosis
  • Psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
  • 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, acquired monocular vision, and any preexisting active conjunctival disease
  • History of neurological conditions that would confound assessment of treatment-emergent neuropathy
  • History of multiple sclerosis or other demyelinating disease and/or Eaton-Lambert syndrome (para-neoplastic syndrome)
  • Previous clinical diagnosis of non-infectious pneumonitis
  • History or evidence of thrombotic disorders within 6 months before first study treatment unless stable on anticoagulation for > 3 months
  • Required used of folate-containing supplements (e.g. folate deficiency)
  • Has a known additional malignancy that is progressing or required active treatment within 3 years of first dose of study treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or other in situ cancers
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with rucaparib and mirvetuximab soravtansine
  • Women who are breastfeeding
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: Phase I Study of Mirvetuximab Soravtansine (IMGN853) and Rucaparib for Recurrent Endometrial, Ovarian, Fallopian Tube or Primary Peritoneal Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the recommended phase II dose (RPTD) of combination mirvetuximab soravtansine and rucaparib camsylate (rucaparib) in patients with recurrent endometrial, epithelial ovarian, primary peritoneal, or fallopian tube carcinoma.

SECONDARY OBJECTIVES:

  1. To determine the safety and tolerability of combination mirvetuximab soravtansine and rucaparib in study patients.

II. To explore the objective antitumor activity (complete and partial response) of combination mirvetuximab soravtansine and rucaparib as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria in the study population.

III. To measure the progression free survival. IV. To evaluate the pharmacokinetics of mirvetuximab soravtansine and rucaparib in combination.

EXPLORATORY OBJECTIVES:

  1. Explore additional biomarkers of response. II. Explore mutation characteristics and frequency with treatment response. III. Evaluate if companion diagnostics can be optimized by combining loss of heterozygosity (LOH) score and level of folate receptor a (FR-alpha) expression, and possible additional predictors of response.

IV. Explore mechanisms of secondary resistance to treatment.

OUTLINE: This is a dose escalation study.

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

After completion of study treatment, participants are followed up at 30 days and then every 3 months for up to a year.

Being tested
Laboratory Biomarker Analysis, Mirvetuximab Soravtansine, Pharmacokinetic Study, Rucaparib Camsylate
Medical subject headings
Fallopian Tube Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Mirvetuximab SoravtansineBiological

    Also called IMGN853, M9346A-sulfo-SPDB-DM4

    Given IV

  • Pharmacokinetic StudyOther

    Also called PHARMACOKINETIC, PK Study

    Correlative studies

  • Rucaparib CamsylateDrug

    Also called 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

    Given PO

Study groups in NCT03552471
Study groupRoleWhat they receive
Treatment (mirvetuximab soravtansine, rucaparib)ExperimentalParticipants 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.
Receives: Other: Laboratory Biomarker Analysis; Biological: Mirvetuximab Soravtansine; Other: Pharmacokinetic Study; Drug: Rucaparib Camsylate

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    based on DLT and toxicity

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

Secondary outcomes (3)

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

    Will be evaluated descriptively using frequencies and percentages

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

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

    Response rate determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

    Measured: Up to 1 year after completion of study treatment

  3. Progression-free survival

    Progression-free survival determined by Kaplan-Meier curves.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jun 2018
  2. Study start12 Jul 2018
  3. Primary completion24 Jun 2022
  4. Study completion19 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03552471
Sponsor's protocol ID
OSU-18007
Other IDs
NCI-2018-00438
Status last verified
Dec 2024
First submitted
26 Apr 2018
Last updated
13 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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