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Study of Carboplatin and Mirvetuximab Soravtansine in First-Line Treatment of Patients Receiving Neoadjuvant Chemotherapy With Advanced-Stage Ovarian, Fallopian Tube or Primary Peritoneal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04606914
Recruitment Status : Not yet recruiting
First Posted : October 28, 2020
Last Update Posted : October 28, 2020
Sponsor:
Information provided by (Responsible Party):
Rebecca Arend, University of Alabama at Birmingham

Brief Summary:
The proposed study design is a single arm Phase II trial to document the feasibility of carboplatin-mirvetuximab - in patients with advanced-stage EOC. Patients with biopsy confirmed, newly diagnosed, advanced-stage serous EOC deemed appropriate for NACT will have their tumors evaluated for FRα receptor over-expression via a centralized immunohistochemical assay (IHC) and identified as appropriate for study participation if IHC staining is PS2+ in >75% of cells (40% of all serous patients). Eligible patients will receive NACT with one cycle of carboplatin, followed by mirvetuximab + carboplatin (if FRα +) every 21 days for three cycles prior to interval cytoreductive surgery (iCRS). A total of 70 will be included in the study. Following completion of 4 cycles total of NACT and after allowing for appropriate recovery of cycle # 4, patients eligible for surgery, will undergo an iCRS. Patients will then complete 3 more cycles of mirvetuximab + carboplatin for a total of 7 intended cycles of treatment. It is up to the treating physician if they want to add bevacizumab to the last 2 cycles or use any type of maintenance therapy. The decision to add bevacizumab or use maintenance therapy does not need to be made upfront. Patients will sign a screening consent form prior to tissue biopsy. If a patient is found to be FRα negative, their treating physician can select the treatment they deem appropriate and the patient will be declared a screen failure. Patients with BRCA mutations are not excluded from this trial and are allowed to receive standard of care maintenance therapy including bevacizumab and/or PARP inhibitors.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Fallopian Tube Primary Peritoneal Cancer Drug: mirvetuximab soravtansine (MIRV; IMGN853) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single-Arm Phase II Study of Carboplatin and Mirvetuximab Soravtansine in First-Line Treatment of Patients Receiving Neoadjuvant Chemotherapy With Advanced-Stage Ovarian, Fallopian Tube or Primary Peritoneal Cancer Who Are Folate Receptor α Positive
Estimated Study Start Date : March 31, 2021
Estimated Primary Completion Date : August 31, 2023
Estimated Study Completion Date : August 31, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Carboplatin

Arm Intervention/treatment
Experimental: neoadjuvant chemotherapy regimen
  • IV Carboplatin AUC 5 (Q21 days) 7 cycles (first cycle is Carbo alone, dosing for C1D1 will be provider's choice)
  • IV Mirvetuximab 6 mg/kg (adjusted ideal body weight) day 1 (Q21 days) 6 cycles (starting with cycle #2)
Drug: mirvetuximab soravtansine (MIRV; IMGN853)
Mirvetuximab soravtansine (also known as IMGN853 and MIRV) is an antibody-drug conjugate (ADC) that consists of a high affinity humanized monoclonal antibody against folate receptor α (FRα, the protein product of the folate receptor 1 [FOLR1] gene) that is conjugated to a cytotoxic maytansinoid by the hindered disulfide succinimidyl 4-(pyridin-2-yl)disulfanyl)-2-sulfo-butyrate linker (sulfo-SPDB) linker. FRα is a glycosyl-phosphatidylinositol (GPI)-linked protein, which shows limited normal tissue expression and high expression on the surface of solid tumors, particularly epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer (referenced herein collectively as EOC), endometrial cancer, non-small cell lung cancer (NSCLC), and renal cell cancer.




Primary Outcome Measures :
  1. progression free survival (PFS) [ Time Frame: Baseline through 2 years ]
    To assess percentage of patients with advanced-stage ovarian, fallopian tube, and peritoneal cancers per Response Evaluation Criteria in Solid Tumors (RACIST)1.1 and Gynecological Cancer Intergroup Cancer antigen 125 (GCIG CA-125) criteria.

  2. Objective response rate (ORR) [ Time Frame: Baseline through 2 years ]
    To assess ORR per iRECIST 1.1 and GCIG CA-125 criteria

  3. Radiographic tumor assessment per RECIST v1.1 criteria [ Time Frame: Baseline through 2 years ]
    Radiographic tumor response by CT or MRI of chest, abdomen, and pelvis using RECIST v1.1


Secondary Outcome Measures :
  1. Serum Cancer Antigen 125 (CA-125) assessments [ Time Frame: Baseline through 2 years ]
    Serum CA-125 will be assessed by the same laboratory throughout the study.

  2. Safety profile of treatment with carboplatin-mirvetuximab soravtansine according to CTCAE v4.03 [ Time Frame: Baseline through 2 years ]
    To determine the nature and degree of toxicity oftreatment with carboplatin-mirvetuximab soravtansine according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Women with biopsy-confirmed high grade serous epithelial ovarian cancer
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have biopsy-confirmed high grade serous epithelial ovarian cancer.
  • Patients must present with stage III or IV disease and be appropriate to receive neoadjuvant chemotherapy
  • Patients must be willing to provide an archival tumor tissue block or slides, or undergo procedure to obtain a new biopsy using a low-risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα positivity
  • Patients must have a performance status of 0 or 1.
  • Patient's tumor must be positive for FRα expression as defined by a score of PS2+ intensity in >75% of cells
  • Patients must have adequate hematologic, liver and kidney functions defined as:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1,500/μL)
  • Platelet count ≥ 100 x 109/L (100,000/μL) without platelet transfusion in the prior 10 days
  • Hemoglobin ≥ 9.0 g/dL
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
  • Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN)
  • Serum albumin ≥ 2 g/dL
  • Patients must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements
  • Women of childbearing potential (WCBP) must agree to use highly effective contraceptive method(s) (as defined in Section 5.8.6 while on MIRV and for at least 4 months after the last dose
  • WCBP must have a negative pregnancy test within the 4 days prior to the first dose of MIRV

Exclusion Criteria:

  • Patients who have previously been treated with a systemic anti-cancer therapy
  • Patients with low-grade serous, endometrioid, clear cell, or mucinous histology
  • Patients with active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, and /or monocular vision
  • Patients with serious concurrent illness or clinically relevant active infection, including, but not limited to the following:
  • History of hepatitis B or C infection (whether or not on active antiviral therapy)
  • History of human immunodeficiency virus (HIV) infection
  • Any other concurrent infectious disease requiring IV antibiotics within 2 weeks prior to the first dose of MIRV
  • Patients with a history of multiple sclerosis (MS) or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
  • Patients with clinically significant cardiac disease including, but not limited to, any of the following:
  • Myocardial infarction ≤ 6 months prior to first dose
  • Unstable angina pectoris
  • Uncontrolled congestive heart failure (New York Heart Association > class II)
  • Uncontrolled ≥ Grade 3 hypertension (per CTCAE)
  • Uncontrolled cardiac arrhythmias
  • Patients with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment
  • Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
  • Patients with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis
  • Patients requiring use of folate-containing supplements (eg, folate deficiency)
  • Patients with prior hypersensitivity to monoclonal antibodies (mAb)
  • Women who are pregnant or breastfeeding
  • Patients who received prior treatment with MIRV or other FRα-targeting agents
  • Patients with untreated or symptomatic central nervous system (CNS) metastases
  • Patients with a history of other malignancy within 3 years prior to enrollment Note: patients with tumors with a negligible risk for metastasis or death (eg, adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04606914


Contacts
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Contact: Rebecca Arend, M.D. 205-934-4986 rarend@uabmc.edu

Locations
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United States, Alabama
University of Alabama at Birmingham Womens & Infants Center
Birmingham, Alabama, United States, 35233
Contact: Rebecca Arend         
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
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Principal Investigator: Rebecca Arend, M.D. University of Alabama at Birmingham
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Responsible Party: Rebecca Arend, Assistant Professor, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT04606914    
Other Study ID Numbers: IRB-300005764
First Posted: October 28, 2020    Key Record Dates
Last Update Posted: October 28, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rebecca Arend, University of Alabama at Birmingham:
First line treatment
Advanced epithelial ovarian cancer
mirvetuximab soravtansine
IMGN853
Additional relevant MeSH terms:
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Ovarian Neoplasms
Peritoneal Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Maytansine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action