Clinical Trials /

Mirvetuximab Soravtansine (IMGN853) and Bevacizumab in Patients With Endometrial Cancer

NCT03836157

Description:

IMGN853 is designed to inhibit cell division and cell growth of folate receptor 1 (FRα)-expressing tumor cells. The purpose of this study is to test the safety of IMGN853 and bevacizumab and see what effects (good and bad) that this combination treatment has on subjects with recurrent endometrial cancer.

Related Conditions:
  • Endometrial Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Mirvetuximab Soravtansine (IMGN853) and Bevacizumab in Patients With Endometrial Cancer
  • Official Title: Phase II Trial of Mirvetuximab Soravtansine (IMGN853) and Bevacizumab in Patients With Endometrial Cancer

Clinical Trial IDs

  • ORG STUDY ID: OUSCC-IMGN-001
  • NCT ID: NCT03836157

Conditions

  • Endometrial Cancer
  • Endometrial Adenocarcinoma
  • Endometrial Serous Adenocarcinoma
  • Endometrial Clear Cell Adenocarcinoma

Interventions

DrugSynonymsArms
Mirvetuximab SoravtansineIMGN853Mirvetuximab and Bevacizumab
BevacizumabMirvetuximab and Bevacizumab

Purpose

IMGN853 is designed to inhibit cell division and cell growth of folate receptor 1 (FRα)-expressing tumor cells. The purpose of this study is to test the safety of IMGN853 and bevacizumab and see what effects (good and bad) that this combination treatment has on subjects with recurrent endometrial cancer.

Detailed Description

      SCREENING: During the screening portion of the study, the subject will need to have tumor
      tissue tested and other exams to determine if s/he may proceed to the treatment part of the
      study. The subject's tumor tissue will be tested from either a previous or recent surgery or
      biopsy to see if it contains the FRα protein. If the tumor is positive and the patient meets
      all other eligibility, then the subject may proceed to treatment.

      TREATMENT: Study drugs (IMGN853 and bevacizumab) will be given by vein (IV) once each cycle
      on day 1 of 21 day cycle.

      Regular cancer care exams, tests, and procedures will occur. Additionally, an eye doctor
      visit with complete eye examination every other treatment cycle. Subjects will also
      self-administer eye drops as prescribed by the eye doctor.

      Study participation is up to three years.
    

Trial Arms

NameTypeDescriptionInterventions
Mirvetuximab and BevacizumabExperimentalMirvetuximab Soravtansine 6mg/kg IV (adjusted ideal body weight), on day 1 of each 21 day cycle. Bevacizumab 15 mg/kg, IV, on day 1 of each 21-day cycle.
  • Mirvetuximab Soravtansine
  • Bevacizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with histological diagnosis of endometrial carcinoma (including others per
             protocol).

          2. Expression of folate receptor alpha (FRα) on either archival tumor or new biopsy is
             required.

          3. Measurable disease

          4. Evidence that the endometrial cancer is advanced, recurrent, or persistent and has
             relapsed or is refractory to curative therapy or established treatments.

          5. At least 1 prior platinum-based chemotherapeutic regimen, but not more than 2 prior
             chemotherapeutic regimens, for management of endometrial carcinoma. Prior treatment
             may include chemotherapy, or chemotherapy/radiation therapy . Chemotherapy
             administered in conjunction with primary radiation as a radio-sensitized therapy will
             be considered a systemic chemotherapy regimen

          6. Female patients 18 years or older

          7. Eastern Cooperative Oncology Group performance status of 0 to 1;

          8. Patient must have archival tumor tissue available from the primary or recurrent cancer
             prior to first dose. If archival tumor sample is not available, tumor sample from new
             biopsy is acceptable.

          9. Patients must have acceptable organ and marrow function as defined per protocol

         10. Time from prior therapy:

               1. Systemic anti-neoplastic therapy: five half-lives or four weeks, whichever is
                  shorter. Hormonal therapy is not considered anti-neoplastic therapy.

               2. 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

         11. Patients must have a life expectancy of at least 3 months

         12. Patients should have no major existing co-morbidities or medical conditions that will
             preclude therapy

         13. Ability to understand and the willingness to sign a written informed consent document,
             and to comply with the requirements of the protocol; with the understanding that
             consent may be withdrawn by the patient at any time without prejudice to future
             medical care.

         14. Female patients of reproductive potential and their male partners must agree to
             practice 1 highly effective method of contraception and 1 additional effective
             (barrier) method at the same time, from the time of signing the informed consent
             through at least twelve weeks after the last dose of IMGN853 and/ or bevacizumab.

        Exclusion Criteria:

          1. Previous treatment with mirvetuximab.

          2. Invasive cancer within the past 2 years. Noninvasive non-melanoma skin cancers are not
             exclusions if they have undergone complete resection.

          3. Untreated or symptomatic central nervous system (CNS) metastases. Patients with
             asymptomatic CNS metastases are eligible provided they have been clinically stable for
             at least 4 weeks prior to first dose of study treatment), have no evidence of new or
             emerging CNS metastasis, and are not using steroids for at least 7 days prior to first
             dose of study treatment.

          4. Unstable angina or myocardial infarction within the previous 6 months; uncontrolled
             hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure
             > 100 mmHg on antihypertensive medications); prior history of hypertensive crisis or
             hypertensive encephalopathy; symptomatic congestive heart failure (NYHA Class III and
             IV); uncontrolled cardiac arrhythmia; clinically-significant vascular disease (e.g.
             aortic aneurysm, or dissecting aneurysm), severe aortic stenosis; clinically
             significant peripheral vascular disease; history of any CNS cerebrovascular ischemia
             or stroke within the last 6 months.

          5. Active pulmonary disease or other coexisting medical condition that would preclude
             full compliance with the study.

          6. Receiving any other investigational agents.

          7. History of prior severe infusion reaction to a monoclonal antibody. Patients with
             known hypersensitivity of Chinese hamster ovary cell products or other recombinant
             human antibodies.

          8. Persisting ≥Grade 2 toxicity (except alopecia) from previous anti-cancer treatment.

          9. Patients with > Grade 1 peripheral neuropathy

         10. 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

               -  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 monocular
                  vision.

         11. 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 within 2
                  weeks of study enrollment

         12. History of cirrhotic liver disease

         13. History or evidence of thrombotic or hemorrhagic disorders within 6 months before
             first study treatment

         14. Required used of folate-containing supplements (e.g. for folate deficiency)

         15. Pregnancy

         16. History of bowel obstruction (including subocclusive disease) related to underlying
             disease within 6 months of study treatment.

         17. Clinically-significant proteinuria defined per protocol
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate of patients who remain progression free
Time Frame:6 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:up to 3 years
Safety Issue:
Description:
Measure:Progression free survival
Time Frame:up to 3 years
Safety Issue:
Description:
Measure:Overall survival
Time Frame:up to 3 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Withdrawn
Lead Sponsor:University of Oklahoma

Trial Keywords

  • Mirvetuximab soravtansine
  • gynecologic cancer

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