- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04606914
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
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
Study Overview
Status
Intervention / Treatment
Detailed Description
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. The selective upregulation of FRα in solid tumors and the potent and selective cytotoxicity of MIRV against FRα-positive tumor cells demonstrated in nonclinical studies and clinical studies to date provide rationale for further investigation of MIRV in the treatment of FRα-positive tumors.
Ovarian cancer is a lethal disease with 22,530 new cases and 13,980 deaths expected in 2019 in the US. The estimated number of new EOC cases in the EU (EU27) in 2012 was 44,149 with 29,758 deaths. The overall 5-year survival for EOC patients is only 44%. Besides the incorporation of a platinum- and taxane-based chemotherapy regimen into the upfront treatment, no major strides have been made to improve overall survival (OS) following EOC diagnosis.
Standard of care chemotherapy includes every 21-day paclitaxel and carboplatin, weekly paclitaxel and every 21-day carboplatin. Recently, bevacizumab was approved to be given with and to follow intravenous chemotherapy in front line ovarian cancer based on the PFS advantage demonstrated in GOG 218 and ICON7. This study continued bevacizumab for 15 cycles post completion of 6 cycles of chemotherapy. In evaluating the morphology of the Kaplan Meier curves from both these trials, it is apparent that there is an inflexion in the curves at the point where the bevacizumab is discontinued. To evaluate whether further continuation of bevacizumab would improve PFS, AGO-OVAR17 (BOOST study) is evaluating 15 versus 30 cycles of bevacizumab following front line chemotherapy. These results are anticipated in 2021. Given the above data, this trial as designed, will not include a specific maintenance portion, but physicians can choice what type of maintenance therapy, if any, they give at the completion of at least 7 cycles of platinum +Mirvetuximab soravtansine.
Despite considerable improvements in primary therapy, 80% of the patients with advanced EOC are expected to relapse during or after treatment with platinum-containing regimens. Disease recurring within 6 months of platinum-based chemotherapy is classified as platinum resistant, whereas, disease recurring longer than 6 months after therapy is termed platinum sensitive.
Those patients with PROC who have received prior bevacizumab, either in the platinum-resistant or in the platinum-sensitive setting, have few options. They typically receive subsequent single-agent chemotherapy. Unfortunately, response rates to single-agent chemotherapy are modest (~10 to 15%) and DOR is typically 4 to 8 months. Similarly, OS is poor (median ~11 to 14 months). Because PROC remains a significant unmet medical need, the National Comprehensive Cancer Network (NCCN) guidelines recommend that platinum-resistant patients participate in clinical trials.
The proposed neoadjuvant chemotherapy regimen is as follows:
IV Carboplatin AUC 5 day 1 (Q21 days) 7 cycles (first cycle is Carbo alone) IV Mirvetuximab 6 mg/kg (adjusted ideal body weight) day 1 (Q21 days) 6 cycles (starting with cycle #2)
Patients will continue to receive MIRV until they present with PD per RECIST 1.1, as assessed by study Investigator, unacceptable toxicity, withdraw consent, or death, whichever comes first, or until the Sponsor terminates the study. Study treatment and/or participation in the study may be discontinued at any time at the discretion of the Investigator. The following may be reasons for the Investigator to remove a patient from the study drug:
The patient suffers an intolerable Adverse Event (AE). Noncompliance, including failure to appear at one or more study visits Study treatment and/or participation in the study may be discontinued at any time at the discretion of the Investigator.
The reason for treatment discontinuation must be captured in the clinical trial database. Any AEs experienced up to the point of discontinuation and 30 days thereafter must be documented. All serious adverse events (SAEs), and those AEs assessed by the Investigator as at least possibly related to study drug should continue to be followed until they resolve or stabilize, whichever comes first. Patients will continue to be followed for OS, after discontinuing study drug.
For purposes of this study, the period of safety observation extends from the time of informed consent until the 30-Day Follow-up visit unless additional follow-up safety information is requested as described in Section 9.3. Short-term follow-up for patients who discontinue study drug without documented PD will be followed per RECIST 1.1 every 12±1 weeks until PD, until the patient starts new anticancer treatment, the patient dies, or the patient withdraws consent, whichever comes first. All patients will be followed every 3±1 months for survival until death, lost to follow-up, withdrawal of consent for survival or until EOS, whichever comes first.
Radiographic tumor evaluation by CT or MRI of chest, abdomen, and pelvis will be performed within 28 days before first dose of study drug, before IDS within 21 days after C4D1, and a minimum of 21 days following C7D1. The same method of radiologic assessment used at Screening must be used at all subsequent radiographic evaluations.
Tumor response will be assessed by the Investigator using RECIST v1.1. Response as determined by the Investigator will be recorded in the clinical trial database.
The sample size will comprise of approximately 70 patients from the University of Alabama at Birmingham.
The primary objective will be feasibility (the proportion of consented patients who successfully obtain biopsy confirmation of disease status and IHC analysis of FRα receptor status prior to starting treatment with mirv). The primary analysis will include all consenting patients. Patients who obtain both the biopsy confirm and are FRα positive will be considered feasibility successes. The remainder of the consenting sample will be considered feasibility failures, regardless of the reason for failure.
Key Secondary Objective will be progression free survival (PFS), percentage disease free at 2 years, ORR prior to interval debulking surgery (IDS) per iRECIST 1.1 and GCIG CA-125 criteria, and percentage of optimal cytoreduction and pathological complete response (PCR) at IDS.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Rebecca Arend, M.D.
- Phone Number: 205-934-4986
- Email: rarend@uabmc.edu
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35233
- Recruiting
- University of Alabama at Birmingham Womens & Infants Center
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Contact:
- Rebecca Arend
-
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: neoadjuvant chemotherapy regimen
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate (ORR)
Time Frame: Baseline through 2 years
|
To assess ORR per iRECIST 1.1 and GCIG CA-125 criteria
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Baseline through 2 years
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Radiographic tumor assessment per RECIST v1.1 criteria
Time Frame: Baseline through 2 years
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Radiographic tumor response by CT or MRI of chest, abdomen, and pelvis using RECIST v1.1
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Baseline through 2 years
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progression free survival (PFS)
Time Frame: Baseline through 2 years
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To assess percentage of patients with advanced-stage ovarian, fallopian tube, and peritoneal cancers per Response Evaluation Criteria in Solid Tumors (RECIST)1.1 and Gynecological Cancer Intergroup Cancer antigen 125 (GCIG CA-125) criteria.
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Baseline through 2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serum Cancer Antigen 125 (CA-125) assessments
Time Frame: Baseline through 2 years
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Serum CA-125 will be assessed by the same laboratory throughout the study.
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Baseline through 2 years
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Safety profile of treatment with carboplatin-mirvetuximab soravtansine according to CTCAE v4.03
Time Frame: Baseline through 2 years
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To determine the nature and degree of toxicity oftreatment with carboplatin-mirvetuximab soravtansine according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03
|
Baseline through 2 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Rebecca Arend, M.D., University of Alabama at Birmingham
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Peritoneal Diseases
- Genital Neoplasms, Female
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Abdominal Neoplasms
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Ovarian Neoplasms
- Peritoneal Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Immunoconjugates
- Maytansine
- Mirvetuximab soravtansine
Other Study ID Numbers
- IRB-300005764
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Sidney Kimmel Cancer Center at Thomas Jefferson...CompletedStage I Breast Cancer | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage... and other conditionsUnited States
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Eve RodlerNot yet recruitingBreast Cancer | Ovarian Cancer | Breast Neoplasm | Breast Carcinoma | Breast Cancer Stage IV | Breast Cancer Stage I | Breast Cancer Stage II | Invasive Breast Cancer | Cancer, Breast | Breast Cancer Stage III | Ovary Cancer | Malignant Tumor of Breast | Ovarian Cancer Stage IIIC | Ovarian Cancer Stage IV | Ovarian Cancer... and other conditionsUnited States
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Clinical Trials on mirvetuximab soravtansine (MIRV; IMGN853)
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ImmunoGen, Inc.CompletedFallopian Tube Cancer | Epithelial Ovarian Cancer | Peritoneal CancerUnited States, Belgium, Spain, Israel, Australia, Ireland, Germany, Italy, Bulgaria, Czechia, Poland
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Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.RecruitingFallopian Tube Cancer | Epithelial Ovarian Cancer | Peritoneal CancerChina
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University of Colorado, DenverImmunoGen, Inc.RecruitingFallopian Tube Cancer | Peritoneal Cancer | Ovary CancerUnited States
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ImmunoGen, Inc.Active, not recruitingFallopian Tube Cancer | Primary Peritoneal Cancer | High Grade Ovarian CancerUnited States, United Kingdom, Belgium, Spain, Canada, Georgia
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ImmunoGen, Inc.Active, not recruitingOvarian Cancer | Fallopian Tube Cancer | Peritoneal CancerUnited States, France, Belgium, Spain, Ireland, Italy, Australia, Canada
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Alessandro SantinImmunoGen, Inc.RecruitingEndometrial CancerUnited States
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Duke UniversityNational Comprehensive Cancer NetworkWithdrawnBreast Cancer Triple NegativeUnited States
-
TakedaNot yet recruiting
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Dana-Farber Cancer InstituteMerck Sharp & Dohme LLC; ImmunoGen, Inc.RecruitingEndometrial CancerUnited States