Study of Cemiplimab in Adults With Cervical Cancer
- Conditions
- Squamous Cell Carcinoma (SCC)Recurrent or Metastatic, Platinum-refractory Cervical Cancer
- Interventions
- Drug: CemiplimabDrug: Investigator Choice (IC) Chemotherapy
- Registration Number
- NCT03257267
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
The primary objective is to compare overall survival (OS) for patients with recurrent or metastatic cervical cancer who have histology of squamous cell carcinoma (SCC) and who have any eligible histology treated with either cemiplimab or investigator's choice (IC) chemotherapy.
The secondary objectives performed among SCC patients and among all eligible histologies (SCC and adenocarcinoma/adenosquamous carcinoma (AC) are:
* To compare progression-free survival (PFS) of cemiplimab versus IC chemotherapy
* To compare objective response rate (ORR) (partial response \[PR\] + complete response \[CR\]) of cemiplimab versus IC chemotherapy per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* To compare the duration of response (DOR) of cemiplimab versus IC chemotherapy
* To compare the safety profiles of cemiplimab versus IC chemotherapy by describing adverse events (AE)
* To compare quality of life (QOL) for patients treated with cemiplimab versus IC chemotherapy using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 608
-
Recurrent, persistent, and/or metastatic cervical cancer with squamous cell histology, for which there is not a curative-intent option (surgery or radiation therapy with or without chemotherapy).
- Acceptable histologies (squamous carcinoma, adenocarcinoma, and adenosquamous carcinoma) as defined in the protocol
-
Tumor progression or recurrence after treatment with platinum therapy (must have been used to treat metastatic, persistent, or recurrent cervical cancer)
-
Patient must have measurable disease as defined by RECIST 1.1.
-
Eastern Cooperative Oncology Group (ECOG) performance status ≤1
-
≥18 years old
-
Adequate organ or bone marrow function
-
Received prior bevacizumab therapy or had clinically documented reason why not administered
-
Received prior paclitaxel therapy or had clinically documented reason why not administered
Key
-
Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
-
Prior treatment with an agent that blocks the PD-1/PD-L1 pathway
-
Prior treatment with other systemic immune-modulating agents that was
- within fewer than 4 weeks (28 days) of the enrollment date, or
- associated with irAEs of any grade within 90 days prior to enrollment, or
- associated with toxicity that resulted in discontinuation of the immune modulating agent
-
Active or untreated brain metastases
-
Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of study drug cemiplimab or IC chemo)
-
Active infection requiring therapy
-
History of pneumonitis within the last 5 years
-
History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments
-
Concurrent malignancy other than cervical cancer and/or history of malignancy other than cervical cancer within 3 years of date of first planned dose of study drug cemiplimab or IC chemo), except for tumors with negligible risk of metastasis or death, such as adequately treated cutaneous squamous cell carcinoma or basal cell carcinoma of the skin or ductal carcinoma in situ of the breast. Patients with hematologic malignancies (eg, chronic lymphocytic leukemia) are excluded.
Note: Other protocol defined Inclusion/Exclusion apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental Therapy Cemiplimab Cemiplimab Control Therapy Investigator Choice (IC) Chemotherapy Investigator choice (IC) chemotherapy
- Primary Outcome Measures
Name Time Method Overall Survival (OS) From first dose up to 90 following last dose (~42 months) Overall survival was defined as the time from randomization to the date of death due to any cause. A participant who had not died was censored at the last known date of contact.
Overall Survival (OS) in the SCC Population From first dose up to 90 following last dose (~42 months) Overall survival was defined as the time from randomization to the date of death due to any cause. A participant who had not died was censored at the last known date of contact.
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Time from randomization to the date of the first documented tumor progression or death due to any cause (assessed up to 40 months) PFS was defined as the time from randomization to the date of the first documented tumor progression (radiographic) or death due to any cause. Participants who did not have a documented tumor progression or death were censored on the date of their last evaluable tumor assessment.
Objective Response Rate (ORR) Assessed by Investigator Using RECIST 1.1 From date of randomization up to 40 months ORR was defined as the number of participants who achieved complete response (CR) or partial response (PR) as per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm) (\<1 centimeter \[cm\]). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Duration of Response (DOR) Assessed Per RECIST 1.1 Time from the date of first response to the date of the first documented progressive disease or death due to any cause (up to 40 months) DOR was defined as the time from the date of first response (CR or PR) to the date of the first documented progressive disease (per RECIST 1.1) or death due to any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm (\<1 cm). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Participants who never progressed while being followed was censored at the last valid tumor measurement. DOR was determined by Kaplan-Meier estimate.
Quality of Life (QoL): Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) of Global Health Status /Quality of Life (GHS/QoL) and Physical Functioning Scales From Cycle 1 Day 1 up to 40 months (Each cycle = 42 days) EORTC QLQ-C30 is a 30-question tool used to assess the overall QoL in cancer participants. It consisted of 15 domains: 1 GHS/QoL scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the GHS/QoL, which are scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100. For the GHS/QoL and 5 functional scales a high score indicates better global health status/functioning and a negative change from baseline indicated less improvement. For the symptom scales, a high score indicates a higher level of symptoms, and a negative change from baseline indicated an improvement in symptoms.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Death From first dose up to 90 following last dose (~36 months) An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A Treatment-emergent adverse event (TEAE) was defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life- threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious TEAEs. Number of participants with TEAEs, serious TEAEs, and TEAEs leading to death were reported.
Number of Participants With New or Worsened Laboratory Results by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE) Grade From first dose up to 90 following last dose (~36 months) Laboratory parameters included hematology, electrolytes, chemistry (other), and liver function. Clinically significant abnormalities were determined by the investigator based on NCI-CTCAE Grade where Grade 1 = Mild, Grade 2 = moderate, Grade 3 = severe; Grade 4 = life threatening or disabling; Grade 5 = death. Participants with at least 1 lab abnormality Graded 3/4 in hematology, electrolytes, chemistry (other), or liver function reported.
Trial Locations
- Locations (104)
First Health of the Carolinas Outpatient Cancer Center
🇺🇸Pinehurst, North Carolina, United States
Liga Norte Riograndense Contra o Câncer
🇧🇷Natal, Rio Grande Do Norte, Brazil
Irmandade da Santa Casa de Misericórdia de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hosptial Sao Lucas da PUC de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
UZLeuven Gynaelologic Oncology
🇧🇪Leuven, Belgium
OLV ziekenhuis Aalst, Medische oncologie- Radiotherapie
🇧🇪Aalst, Belgium
Fundação Pio XII - Hospital de Câncer de Barretos
🇧🇷Barretos, São Paulo, Brazil
Institut Bordet
🇧🇪Brussels, Belgium
University Hospital of Ioannina
🇬🇷Ioannina, Greece
General Hospital of Athens Alexandra
🇬🇷Athens, Greece
State Autonomous Healthcare Institution ,Republican Clinical Oncological Dispensary of the Ministry of Healthcare of the Tatarstan Republic
🇷🇺Kazan, Tatarstan, Russian Federation
MacKay Memorial Hospital
🇨🇳Taipei City, Taiwan
Saitama Medical University
🇯🇵Saitama, Saitama Prefecture, Japan
A. Tsyb Medical Radiological Research Center
🇷🇺Obninsk, Kaluga, Russian Federation
State Budgetary Institution of Healthcare, Clinical Oncology Dispensary #1 of Ministry of Health of Krasnodar Region
🇷🇺Krasnodar, Krasnodar Territory, Russian Federation
Center and Institute of Oncology Gliwice
🇵🇱Gliwice, Poland
Centrum Onkologii Ziemi Lubelskiej im sw. Jana z Dukli
🇵🇱Lublin, Poland
Budgetary Institution of Healthcare of Omsk region Clinical Oncology Dispensary
🇷🇺Omsk, Russian Federation
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
Szpitale Pomorskie
🇵🇱Gdynia, Poland
Regional Budgetary Institution of Healthcare Ivanovo Regional Oncology Dispensary
🇷🇺Ivanovo, Ivanovo Region, Russian Federation
Saint- Petersburg State Budgetary institution of Healthcare "City Clinical Oncological Dispensary"
🇷🇺Saint Petersburg, Russian Federation
National Cancer Center
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
University of California Irvine
🇺🇸Orange, California, United States
Cancer Research for the Ozarks
🇺🇸Springfield, Missouri, United States
New York Presbyterian Queens
🇺🇸Flushing, New York, United States
St. George Hospital
🇦🇺Kogarah, New South Wales, Australia
Northern NSW Health District, The Tweed Hospital
🇦🇺Tweed Heads, New South Wales, Australia
Royal Brisbane & Women's Hospital
🇦🇺Herston, Queensland, Australia
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
St. John of God Subiaco Hospital
🇦🇺Subiaco, Western Australia, Australia
Cliniques universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
CHC Saint Joseph
🇧🇪Liège, Belgium
CHU Liège
🇧🇪Liège, Belgium
CHU UCL Namur site Sainte Elisabeth
🇧🇪Namur, Belgium
Centro de Novos Tratamentos Itajai
🇧🇷Itajai, Santa Catarina, Brazil
Instituto Nacional de Cancer - INCA
🇧🇷Rio de Janeiro, Brazil
Instituto de Pesquisas Clinicas para Estudos Multicentricos - IPCEM
🇧🇷Caxias do Sul, Brazil
Instituto COI de Pesquisa
🇧🇷Rio de Janeiro, Brazil
Tom Baker Cancer Center
🇨🇦Calgary, Alberta, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Hospital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
Hopital Notre-Dame du Centre Hospitalier de l'Universite de Montreal
🇨🇦Montréal, Quebec, Canada
Jewish General Hospital
🇨🇦Montréal, Quebec, Canada
Euromedica General Clinic, B'Oncology Clinic
🇬🇷Thessaloniki, Greece
Azienda Ospedaliero Universitaria di Bologna
🇮🇹Bologna, Italy
Asst Lecco
🇮🇹Lecco, Italy
U.O Oncologia Medica P.O Vito Fazzi
🇮🇹Lecce, Italy
Irst Irccs
🇮🇹Meldola, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
AUSL, IRCCS di Reggio Emilia
🇮🇹Reggio Emilia, Italy
Fondazione Policlinico Agostino Gemelli IRCCS di Roma
🇮🇹Roma, Italy
Regina Elena National Cancer Institute
🇮🇹Rome, Italy
Shikoku Cancer Center
🇯🇵Matsuyama, Ehime, Japan
Ehime University Hospital
🇯🇵Toon, Ehime, Japan
Kurume University Hospital
🇯🇵Kurume, Fukuoka, Japan
Fukui University Hospital
🇯🇵Yoshida-gun, Fukui, Japan
University of the Ryukyus Hospital
🇯🇵Nakagami-gun, Okinawa, Japan
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
St. Marianna University School of Medicine Hospital
🇯🇵Kawasaki, Kanagawa, Japan
Saitama Cancer Center
🇯🇵Saitama, Tokyo, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Koto-Ku, Tokyo, Japan
Kyorin University Hospital
🇯🇵Mitaka, Tokyo, Japan
Kagoshima City Hospital
🇯🇵Kagoshima, Japan
National Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Bialostockie Centrum Onkologii
🇵🇱Białystok, Poland
State Budgetary Healthcare Institution Leningrad Regional Oncological Dispensary (SBHI "LROD")
🇷🇺Vsevolozhsk, Leningrad Region, Russian Federation
State Budgetary Institution of Healthcare "Orenburg Regional Clinical Oncology Dispensary"
🇷🇺Orenburg, Russian Federation
Vall d´Hebron University Hospital
🇪🇸Barcelona, Spain
Hospital Reina Sofia
🇪🇸Cordoba, Spain
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
Instituto Catalan de Oncologia de Gerona
🇪🇸Girona, Spain
Hospital Universitario HM Sanchinarro CIOCC
🇪🇸Madrid, Spain
Koo-Foundation Sun Yat-Sen Cancer Center
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
NHS Greater Glasgow and Clyde Beatson, West of Scotland Cancer care
🇬🇧Glasgow, United Kingdom
Royal Marsden NHS Foundation Trust, Chelsea
🇬🇧London, United Kingdom
University College Hospital
🇬🇧London, United Kingdom
Laura and Issac Perlmutter Cancer Center at NYU Langone
🇺🇸New York, New York, United States
Arizona Oncology Associates
🇺🇸Tucson, Arizona, United States
Northwell Health
🇺🇸Lake Success, New York, United States
London Health Sciences Centre
🇨🇦London, Ontario, Canada
General Hospital of Patras
🇬🇷Patras, Greece
Keimyung University Dongsan Medical Center
🇰🇷Daegu, Korea, Republic of
Greater Poland Cancer Center
🇵🇱Poznań, Poland
State Budgetary Healthcare Institution "Oncology Dispensary" of Ministry of Healthcare of the Kabardino-Balkarian Republic
🇷🇺Nal'chik, Kabardino-Balkarian, Russian Federation
Hospital Universitario Son Espases
🇪🇸Palma de Mallorca, Illes Balears, Spain
Hospital Virgen de la Victoria
🇪🇸Malaga, Spain
Fundacion Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
Hospital Universitario La Fe
🇪🇸Valencia, Spain
Hospital Clinico Universitario Lozano Blesa
🇪🇸Zaragoza, Spain
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
Royal Marsden NHS Foundation Trust, Sutton
🇬🇧Sutton, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Texas Oncology, P.A.
🇺🇸Austin, Texas, United States
British Columbia Cancer Agency
🇨🇦Vancouver, British Columbia, Canada
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia