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Carboplatin and Mirvetuximab Soravtansine in First-Line Treatment of Patients Receiving Neoadjuvant Chemotherapy for Folate Receptor Alpha Positive Advanced-Stage Ovarian, Fallopian Tube or Primary Peritoneal Cancer
Trial Status: active
This phase II trial tests whether mirvetuximab soravtansine and carboplatin works to shrink tumors in patients with folate receptor alpha positive ovarian, fallopian tube or primary peritoneal cancer (that has spread to other places in the body (advanced). Mirvetuximab soravtansine is a monoclonal antibody, called mirvetuximab, linked to a chemotherapy drug called soravtansine. Mirvetuximab attached to folate receptor 1 (FOLR1) positive cancer cells in a targeted way and delivers soravtansine to kill them. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Giving mirvetuximab soravtansine and carboplatin may kill more tumor cells in patients with advanced stage ovarian, fallopian tube or primary peritoneal cancer.
Inclusion Criteria
Patients must have biopsy-confirmed epithelial ovarian cancer prior to treatment with mirvetuximab soravtansine (MIRV).
* Note: Patients may sign consent prior to a histologic diagnosis in order to obtain tissue for folate receptor alpha (FRalpha) testing as long as there is a reasonable suspicion for advanced ovarian cancer by the treating oncologist (i.e., radiographic evidence of carcinomatosis, omental caking, or pleural effusions; CA-125/ carcinoembryonic antigen [CEA] ratio >= 25; and/or malignant ascites).
Patients must present with stage III or IV disease and be eligible 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 FRalpha positivity.
Patients must have a performance status of 0, 1, or 2.
Patient’s tumor must be positive for FRalpha expression as defined by a score of 2+ in 75% of cells.
Platelet count >= 100 x 10 ^ 9/L (100,000/uL) 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 or their legally authorized representative 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 have a negative pregnancy test within 4 days prior to the first dose of carboplatin and must agree to immediately begin using highly effective contraceptive method(s) until at least 6 months after the last dose of the study drugs.
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 intravenous (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 Common Terminology Criteria for Adverse Events [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 FRalpha-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.
Additional locations may be listed on ClinicalTrials.gov for NCT04606914.
I. To assess the feasibility of obtaining tissue, assessing alpha-folate receptor status, and initiating treatment based on this data in advanced-stage ovarian, fallopian tube, or peritoneal cancer (epithelial ovarian cancer [EOC]) patients treated with carboplatin-mirvetuximab soravtansine (NACT) using a every (Q) 21-day schedule.
SECONDARY OBJECTIVES:
I. To assess safety and feasibility of treatment with carboplatin-mirvetuximab soravtansine (NACT) using a Q 21-day schedule in advanced-stage EOC patients, without an unacceptable interval debulking surgery (IDS) delay.
II. To assess progression free survival (PFS).
III. To assess percentage disease free at 2 years.
IV. Objective response rate (ORR) prior to IDS per Response Evaluation Criteria in Solid Tumors (iRECIST) 1.1 and Gynecologic Cancer Intergroup (GCIG) CA-125 criteria.
V. To assess percentage of optimal cytoreduction and pathological complete response (pCR) at IDS.
EXPLORATORY OBJECTIVE:
I. Folate receptor alpha testing will be an integral biomarker (by immunohistochemistry [IHC]).
OUTLINE:
Patients receive carboplatin intravenously (IV) on day 1. Beginning cycle 2, patients also receive mirvetuximab soravtansine IV on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo interval debulking surgery. Patients then receive carboplatin IV and mirvetuximab soravtansine IV on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 12 weeks for the 1st year.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationUniversity of Alabama at Birmingham Cancer Center