Clinical Trials /

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

NCT03552471

Description:

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.

Related Conditions:
  • Endometrial Carcinoma
  • Fallopian Tube Carcinoma
  • Low Grade Ovarian Serous Adenocarcinoma
  • Ovarian Carcinoma
  • Ovarian Clear Cell Adenocarcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Mirvetuximab Soravtansine and Rucaparib Camsylate in Treating Participants With Recurrent Endometrial, Ovarian, Fallopian Tube or Primary Peritoneal Cancer
  • Official Title: Phase I Study of Mirvetuximab Soravtansine (IMGN853) and Rucaparib for Recurrent Endometrial, Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Clinical Trial IDs

  • ORG STUDY ID: OSU-18007
  • SECONDARY ID: NCI-2018-00438
  • NCT ID: NCT03552471

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

Interventions

DrugSynonymsArms
Mirvetuximab SoravtansineIMGN853, M9346A-sulfo-SPDB-DM4Treatment (mirvetuximab soravtansine, rucaparib)
Rucaparib Camsylate8-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 PhosphateTreatment (mirvetuximab soravtansine, rucaparib)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. 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:

      I. 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:

      I. 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.
    

Trial Arms

NameTypeDescriptionInterventions
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.
  • Mirvetuximab Soravtansine
  • Rucaparib Camsylate

Eligibility Criteria

        Inclusion Criteria:

          -  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

               -  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

        Exclusion Criteria:

          -  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)

               -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended phase II dose (RPTD) of mirvetuximab soravtansine and rucaparib camsylate in combination
Time Frame:At the end of Cycle 1 (each cycle 15 days)
Safety Issue:
Description:based on DLT and toxicity

Secondary Outcome Measures

Measure:Incidence of adverse effects graded according to CTCAE v. 4.0
Time Frame:while on study drug and up to 30 days after (through study treatment completion, an average of 1 year)
Safety Issue:
Description:Will be evaluated descriptively using frequencies and percentages
Measure:Objective anti-tumor activity (complete and partial response) of mirvetuximab soravtansine and rucaparib in combination
Time Frame:Up to 1 year after completion of study treatment
Safety Issue:
Description:Response rate determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Measure:Progression-free survival
Time Frame:From start of treatment up to 1 year after completion of study treatment
Safety Issue:
Description:Progression-free survival determined by Kaplan-Meier curves.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ohio State University Comprehensive Cancer Center

Last Updated

July 13, 2018