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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02631876
Other study ID # IMGN853-0403
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date March 2, 2016
Est. completion date January 2020

Study information

Verified date September 2020
Source ImmunoGen, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a Phase 3, open label, randomized study designed to compare the safety and efficacy of mirvetuximab soravtansine to that of selected single-agent chemotherapy (Investigator's choice) in women with platinum-resistant FR-alpha positive advanced EOC, primary peritoneal cancer and/or fallopian tube cancer.


Description:

Participants will be randomized to either mirvetuximab soravtansine or investigator's choice chemotherapy.


Recruitment information / eligibility

Status Completed
Enrollment 366
Est. completion date January 2020
Est. primary completion date January 2019
Accepts healthy volunteers No
Gender Female
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Participants must be diagnosed with advanced epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer

- Participants must have folate receptor alpha positive tumor expression as defined in the protocol

- Participants must have platinum-resistant ovarian cancer, defined as progression within 6 months from completion of a minimum of four cycles of platinum-containing therapy.

- Participants must have received at least one but no more than three prior systemic treatment regimens and for whom single-agent chemotherapy is appropriate as the next line of treatment

- Participants must have at least one lesion that meets the definition of measurable disease by RECIST 1.1

Exclusion Criteria:

- Diagnosis of clear cell, low grade ovarian cancer or mixed tumors

- Participants with primary platinum-refractory disease

- Serious concurrent illness or clinically relevant active infection as defined in the protocol

- Prior treatment with mirvetuximab soravtansine

- Women who are pregnant or breast feeding

Study Design


Intervention

Drug:
Mirvetuximab soravtansine
Mirvetuximab Soravtansine will be administered per dose and schedule specified in the arm.
Paclitaxel
Paclitaxel will be administered per dose and schedule specified in the arm.
Pegylated liposomal doxorubicin
Pegylated liposomal doxorubicin will be administered per dose and schedule specified in the arm.
Topotecan
Topotecan will be administered per dose and schedule specified in the arm.

Locations

Country Name City State
Belgium Cliniques Universitaires Saint-Luc Brussels
Belgium AZ Groeninge - Oncology Centre Kortrijk
Belgium Universitaire Ziekenhuizen (UZ) Leuven-Gasthuisberg Leuven
Belgium Centre Hospitalier de l'Ardenne Libramont
Bosnia and Herzegovina University Clinical Center of Republic of Srpska Banja Luka
Canada Tom Baker Cancer Centre Calgary Alberta
Canada Cross Cancer Institute Edmonton Alberta
Canada Juravinski Cancer Centre Hamilton Ontario
Canada Hopital de la CitedelaSante Laval Quebec
Canada London Health Sciences Centre London Ontario
Canada Centre hospitalier de l'Université de Montréal Montreal Quebec
Canada McGill University Health Centre - Glen Site Montréal Quebec
Canada The Ottawa Hospital Cancer Centre Ottawa Ontario
Canada Princess Margaret Cancer Centre Toronto Ontario
Canada Sunnybrook Research Institute - Odette Cancer Centre Toronto Ontario
Czechia Porodnicka A Gynekologicka Klinika Hradec Králové
Czechia University Hospital Ostrava Ostrava Poruba
Czechia Onkologicke oddeleni Krajske nemocnice T. Bati, a.s., Zlin Zlín
France Institut de Cancerologie de L'Ouest - site Paul Papin Angers
France CHRU Jean Minjoz Besançon
France Institut Bergonie Bordeaux
France Cochin Hospital Paris
France Hôpital Croix St-Simon Paris
France Centre Hospitalier Lyon-Sud Pierre-Bénite
France Centre Armoricain de radiotherapie, Imagerie Medicale et Oncol Plérin
France Centre Eugene Marquis Rennes
France Institut Curie-Hopital Rene Huguenin Saint-Cloud
France Institut Claudius Regaud Toulouse
France Institut de Cancerologie de Lorraine Vandœuvre-lès-Nancy
France Gustave Roussy Institution Villejuif
Ireland Bon Secours Hospital Cork
Ireland Mater Private Hospital and Mater Misericordiae University Hospital Dublin
Italy Azienda Ospedaliero Universitaria di Bologna Policlinico S. Orsola-Malpighi Bologna
Italy Azienda Sanitaria Locale (ASL) Brindisi
Italy Azienda Unita Sanitaria Locale di Ravenna Faenza
Italy Romagnolo per lo Studio e la Cura dei Tumori IRST-IRCCS - Oncologia medica Meldola (FC)
Italy Fondazione IRCCS National Cancer Institute Milan
Italy Ospedale San Raffaele Milan
Italy Istituto Europeo di Oncologia Milano MI
Italy Istituto Nazionale Tumori- G. Pascale Naples
Italy Policlinico Universitario Agostino Gemelli Roma
Russian Federation LLC "VitaMed" Moscow
Russian Federation State Budget-Funded Healthcare Institution of Novosibirsk Oblast "Novosibirsk Oblast Oncology Dispensary" Novosibirsk
Russian Federation Budget-Funded Healthcare Institution of Omsk Oblast "Clinical Oncology Dispensary" Omsk
Russian Federation State Budget Institution of Health "Leningrad Regional Oncologicacal Dispensary" Saint Petersburg
Serbia Oncology and Radiology Institute Serbia Belgrade
Serbia Clinical Centre Nis, Oncology Clinic Niš
Serbia Oncology Institute Vojvodina Sremska Kamenica
Spain Hospital Teresa Herrera (CHUACoruña) A Coruña
Spain ICO Hospital Germans Trias i Pujol Badalona Barcelona
Spain Hospital Vall D'Hebron Barcelona
Spain Institut Català d'Oncologia - Unitad de Investigación Clínica Barcelona
Spain IOR - Hospital Quiron Dexeus Barcelona
Spain Hospital Reina Sofia Córdoba
Spain Onkologikoa Donostia San Sebastian Gipuzkoa
Spain Complejo Hospitalario Granada Granada
Spain Hospital Universitario Gregorio Maranon Madrid
Spain Hospital Universitario HM Sanchinarro Madrid
Spain Hospital Universitario Ramon Y Cajal Madrid
Spain MD Anderson Cancer Center - Madrid Madrid
Spain Servicio de Oncología Médica Hospital Universitario La Paz Madrid
Spain Hospital Regional Universitario Malaga - Hospital Materno Infantil de Málaga Malaga
Spain Hospital Son Llatzer (HSLL) Palma de Mallorca
Spain Instituto Valenciano de Oncologia Valencia
Switzerland Hopitaux Universitaires de Geneve Geneve
Switzerland Kantonsspital Winterthur Zurich
Switzerland Kantonsspital Winterthur, Medizinische Onkologie Winterthur Zurich
United Kingdom University Hospitals Coventry & Warwickshire NHS Trust, Arden Cancer Centre Coventry
United Kingdom Beatson West of Scotland Cancer Centre Glasgow Scotland
United Kingdom UCL Cancer Institute London England
United Kingdom The Christie NHS Foundation Trust Manchester England
United Kingdom Mount Vernon Cancer Centre Northwood
United Kingdom Nottingham University Hospitals NHS Trust - City Hospital Nottingham England
United Kingdom Peterborough City Hospital Peterborough Great Britain
United Kingdom Lancashire Teaching Hospitals NHS Foundation Trust - Royal Preston Hospital Preston England
United Kingdom Cancer,Haematology and Physics Directorate, Cancer Centre Royal Stoke University Stoke-on-Trent Staffordshire
United Kingdom The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital (RMH) Sutton England
United Kingdom The Royal Wolverhampton Hospitals NHS Trust - New Cross Hospital - GOW Wolverhampton England
United States The University of New Mexico Comprehensive Cancer Center - Memorial Medical Center Albuquerque New Mexico
United States Georgia Regents University (GRU)-Medical College of Georgia (MCG) - Cancer Center Augusta Georgia
United States Texas Oncology-Austin Central Austin Texas
United States University of Alabama at Birmingham Birmingham Alabama
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
United States MD Anderson Cancer Center - Cooper Health Camden New Jersey
United States Hollings Cancer Center Charleston South Carolina
United States Levine Cancer Institute - Carolinas Medical Center Charlotte North Carolina
United States Rush University Medical Center Chicago Illinois
United States University of Cincinnati Medical Center Cincinnati Ohio
United States Cleveland Clinic Cleveland Ohio
United States Fairview Hospital, Moll Pavilion Cancer Center Cleveland Ohio
United States OSU Wexner Medical Center Columbus Ohio
United States Women's Cancer Care Covington Louisiana
United States University of Texas Southwestern Medical Center Dallas Texas
United States Henry Ford Hospital Detroit Michigan
United States Karmanos Cancer Institute Detroit Michigan
United States Texas Oncology - Fort Worth Fort Worth Texas
United States Sudarshan Sharma LTD Hinsdale Illinois
United States Community Health Network, Inc. Indianapolis Indiana
United States Indiana University School of Medicine Indianapolis Indiana
United States Kadlec Clinic Hematology & Oncology Kennewick Washington
United States Dartmouth-Hitchcock Medical Center Lebanon New Hampshire
United States UCLA Women's Health Clinical Research Unit - OBGYN Los Angeles California
United States Norton Cancer Institute Louisville Kentucky
United States Hillcrest Hospital Mayfield Ohio
United States Froedtert and Medical College of Wisconsin Milwaukee Wisconsin
United States Yale University School of Medicine New Haven Connecticut
United States Ochsner Clinic Foundation New Orleans Louisiana
United States Icahn School of Medicine at Mount Sinai New York New York
United States Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York
United States Memorial Sloan Kettering Cancer Center and (MSK Monmouth) and ( MSK Westchester) New York New York
United States Norwalk Hospital/WCHN Norwalk Connecticut
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States University of Pennsylvania Philadelphia Pennsylvania
United States Magee - Womens Hospital of UPMC Pittsburgh Pennsylvania
United States Women & Infants of Rhode Island Providence Rhode Island
United States Center of Hope Reno Nevada
United States University of California San Diego Medical Center San Diego California
United States California Pacific Medical Center San Francisco California
United States Florida State University College of Medicine Sarasota Florida
United States WK Physician Network Clinical Research Shreveport Louisiana
United States Holy Cross Hospital Silver Spring Maryland
United States Mercy Women's Oncology Springfield Missouri
United States Overlook Medical Center Summit New Jersey
United States Arizona Oncology Associates, PC - HAL Tempe Arizona
United States Texas Oncology - The Woodlands, Gynecologic Oncology The Woodlands Texas
United States Arizona Oncology Associates, PC - HOPE Tucson Arizona
United States Oklahoma Cancer Specialists and Research Institute, LLC Tulsa Oklahoma
United States Texas Oncology-Tyler Tyler Texas
United States Kaiser Permanente Medical Center Vallejo California
United States University of Massachusetts Memorial Medical Center Worcester Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
ImmunoGen, Inc. Gynecologic Oncology Group

Countries where clinical trial is conducted

United States,  Belgium,  Bosnia and Herzegovina,  Canada,  Czechia,  France,  Ireland,  Italy,  Russian Federation,  Serbia,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Progression-Free Survival (PFS), as Assessed by BIRC Per RECIST Version 1.1 in All Participants Randomized to the Study PFS was defined as the time from randomization until PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the sum of the longest diameters (SoD) of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. From the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Primary PFS, as Assessed by BIRC Per RECIST Version 1.1 in Participants With High Folate Receptor Alpha Level (= 75% of Tumor Staining) PFS was defined as the time from randomization until PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. From the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Secondary Objective Response Rate (ORR): Percentage of Participants With Objective Response, as Assessed by BIRC Per RECIST1.1 ORR was defined as percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR: At least 30 percent (%) decrease in the SoD of target lesions, taking as reference the baseline SoD. From randomization until first BOR of CR or PR (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Secondary Overall Survival (OS) OS was defined as the time from the date of randomization until the date of death from any cause. Participants who did not experience the event of death were censored at their last date known to be alive. OS was estimated using the Kaplan-Meier method. From the date of randomization until the time of death (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Secondary Number of Participants Achieving at Least a 15% (= 15-Point) Absolute Improvement From Baseline on the EORTC QLQ-OV28 Abdominal/Gastrointestinal (AB/GI) Symptom Subscale at Week 8/9 Assessment European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Ovarian Cancer 28 (EORTC QLQ-OV28) is a 28-item ovarian cancer supplemental module. It comprises of 6 symptom scales (AB/GI symptoms, peripheral neuropathy, other chemotherapy side-effects, hormonal symptoms, body image, attitude to disease, treatment), and sexual functioning. Participants were asked to indicate extent to which they experienced AB/GI symptoms. Participants responded on a scale of 1-4(1=not at all, 2=a little, 3=quite a bit, 4=very much) to following: Did you have abdominal pain? Did you have a bloated feeling in your abdomen? Did you have problems with your clothes feeling too tight? Did you experience any change in bowel habit as a result of your disease or treatment? Were you troubled by passing wind/gas/flatulence? Have you felt full too quickly after beginning to eat? Have you had indigestion/heartburn? Data were transformed to a scale from 0-100. Lower scores=better health. Baseline, Week 8/9
Secondary Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Adverse event (AE): any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to study drug. Severity: graded per National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) v4.03 on following scale: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death. Relation of AE to treatment was determined by investigator. Serious AEs: death, life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent/significant disability or incapacity, congenital anomaly or birth defect, or an important medical event that required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: any AE that emerged on or after the first dose, and within 30 days of the last dose. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported AEs module. From first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Secondary Gynecologic Cancer Intergroup (GCIG) CA-125 Response Rate: Percentage of Participants With GCIG CA-125 Confirmed Clinical Responses CA-125 Response rate wasdefined as the number of participants with a CA-125 confirmed response divided by the number of participants in the CA-125 response-evaluable population multiplied by 100. From first dose of study drug until CA-125 response (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Secondary PFS, as Assessed by Investigator Per RECIST Version 1.1 PFS was defined as the time from randomization until PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. From the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Secondary Duration of Response (DOR), as Assessed by BIRC Per RECIST v1.1 DOR was defined as the time from the date of the first response (CR or PR), whichever was recorded first, until the date of PD. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. DOR was only defined for participants who had a BOR of CR or PR using the method of Kaplan-Meier. From the date of first response (CR or PR) until the date of PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Secondary Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-methyl DM4 PK parameters were calculated using standard non-compartmental methods. Pre-dose and within 5 minutes after mirvetuximab soravtansine infusion on Day 1 of Cycles 1 and 3; and Day 8 and 15 of Cycles 1 and 3
Secondary Number of Participants With Anti-Drug Antibodies (ADA) An electrochemiluminescent method was used for the detection of anti-mirvetuximab soravtansine antibodies in plasma from samples collected in dipotassium ethylenediaminetetraacetic acid (K2EDTA) tubes. The qualitative assay was designed to detect anti-mirvetuximab soravtansine antibodies in human plasma. Pre-dose and within 5 minutes after mirvetuximab soravtansine infusion on Day 1 of Cycles 1, 2, and 4; pre-dose on Day 1 of Cycle 6
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