Carboplatin-paclitaxel With Retifanlimab or Placebo in Participants With Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (POD1UM-303/InterAACT 2).

Squamous Cell Carcinoma of the Anal Canal Clinical Trial

Official title:

A Phase 3 Global, Multicenter, Double-Blind Randomized Study of Carboplatin-Paclitaxel With INCMGA00012 or Placebo in Participants With Inoperable Locally Recurrent or Metastatic Squamous Cell Carcinoma of the Anal Canal Not Previously Treated With Systemic Chemotherapy (POD1UM-303/InterAACT 2)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04472429
• Other study ID #: INCMGA 0012-303
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 12, 2021
• Est. completion date: October 27, 2024

Study information

• Verified date: June 2024
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a Phase 3 global, multicenter, placebo-controlled double-blind randomized study that will enroll participants with inoperable locally recurrent or metastatic SCAC not previously treated with systemic chemotherapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 308
• Est. completion date: October 27, 2024
• Est. primary completion date: October 24, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Able to comprehend and willing to sign a written ICF for the study.
• Are 18 years of age or older (or as applicable per local country requirements).
• Histologically or cytologically verified, inoperable locally recurrent or metastatic SCAC.
• No prior systemic therapy other than the following: a. Chemotherapy administered concomitantly with radiotherapy as a radiosensitizing agent is permitted. b. Prior neoadjuvant or adjuvant therapy if completed = 6 months before study entry.
• Has measurable disease per RECIST v1.1 as determined by local site investigator/radiology assessment. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion.
• Able and willing to provide adequate tissue sample and whole blood sample with central testing result prior to randomization. Biopsy for archival samples should have occurred within 9 months prior to randomization.
• ECOG performance status 0 to 1.
• If HIV-positive, then must be stable as defined by: a. CD4+ count = 200/µL, b. Undetectable viral load per standard of care assay, c. Receiving antiretroviral therapy (ART/HAART) for at least 4 weeks prior to study enrollment, and have not experienced any HIV-related opportunistic infection for at least 4 weeks prior to study enrollment.
• Willingness to avoid pregnancy or fathering children

Exclusion Criteria:

• Has received prior PD-(L)1 directed therapy
• Has received prior radiotherapy with or without radiosensitizing chemotherapy within 28 days of Cycle 1 Day 1 except for palliative radiation (30 Gy or less) which is restricted for 14 days of Cycle 1 Day 1 (note: all toxicities associated should have resolved to Grade = 1).
• Participants with laboratory outside of the protocol defined ranges.
• History of second malignancy within 3 years (with exceptions).
• Clinically significant pulmonary, cardiac, gastrointestinal or autoimmune disorders.
• Active bacterial, fungal, or viral infections, including hepatitis A, B, and C and IV antibiotic use within 7 days of Cycle 1 Day 1.
• Receipt of a live vaccine within 28 days of planned start of study therapy.
• History of organ transplant, including allogeneic stem cell transplantation.
• Known active CNS metastases and/or carcinomatous meningitis.
• Known hypersensitivity to platinum, paclitaxel, another monoclonal antibody, or any of the excipients that cannot be controlled with standard measures (eg, antihistamines, corticosteroids).
• Participant is pregnant or breastfeeding.
• Current use of protocol defined prohibited medication.
• Has pre-existing peripheral neuropathy that is = Grade 2 by CTCAE v5.
• Inability or unlikely, in the opinion of the investigator, to comply with the Protocol requirements

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma of the Anal Canal

Intervention

Drug:
• carboplatin
carboplatin will be administered intravenous on Day 1 of each 28 day cycle
• paclitaxel
paclitaxel will be administered intravenous on Days 1,8, and 15 of each 28 day cycle
• retifanlimab
retifanlimab will be administered intravenous on Day 1 of each 28 day cycle

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Monash Medical Centre Clayton	Clayton	Victoria
Australia	Princess Alexandra Hospital Australia	Woolloongabba	Queensland
Belgium	Zna Middelheim	Antwerpen
Belgium	Ulb Hospital Erasme	Bruxelles
Denmark	Herlev Og Gentofte Hospital	Herlev
Denmark	Vejle Hospital	Vejle
France	Institut de Cancerologie de L Ouest - Site Paul Papin	Angers Cedex 2
France	Chu Besancon Hospital Jean Minjoz	Besançon
France	Centre Hospitalier Universitaire de Bordeaux	Bordeaux Cedex
France	Centre Leon Berard	Lyon
France	Chu Hopital de La Timone	Marseille Cedex 5
France	Institut Du Cancer de Montpellier	Montpellier
France	Centre Antoine Laccassagne	Nice
France	Hospital Universitaire Pitie-Salpetriere	Paris Cedex 13
France	Hospital de La Miletrie	Poitiers Cedex
France	Chu de Rennes - Hospital Pontchaillou	Rennes Cedex 09
France	Hopital Charles Nicolle Chu Rouen Hospital de Bois-Guillaume	Rouen Cedex
France	Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau	Saint Herblain
France	Institut de Cancerologie de Strasbourg	Strasbourg
France	Chu Toulouse Hopital Rangueil	Toulouse Cedex 9
France	Institut Gustave Roussy	Villejuif Cedex
Germany	Universitatsklinikum Bonn Aoer	Bonn
Germany	University Clinic Carl Gustav Carus Technical University Dresden	Dresden
Germany	Asklepios Klinik Altona	Hamburg
Italy	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milan
Italy	Fondazione Irccs Ca Granda Ospedale Maggiore	Milan
Italy	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milano
Italy	Comitato Etico Fondazione Irccs Istituto Nazionale Dei Tumori Milano	Milano
Italy	European Institute of Oncology	Milano
Italy	University Di Cagliari-Presidio Policlinico Monserrato	Monserrato
Italy	Azienda Ospedaliera Universitaria University Degli Studi Della Campania Luigi Vanvitelli	Napoli
Italy	Iov - Istituto Oncologico Veneto Irccs	Padova
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Ospedale Degli Infermi	Rimini
Italy	I.R.C.C.S. Casa Sollievo Della Sofferenza	San Giovanni Rotondo
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti	Torrette
Japan	National Cancer Center Hospital	Chuo-ku
Japan	Kyushu University Hospital	Fukuoka-shi
Japan	Saitama Medical University International Medical Center	Hidaka-shi
Japan	Aichi Cancer Center Hospital	Nagoya-shi
Japan	Osaka International Cancer Institute	Osaka-shi
Japan	Tohoku University Hospital	Sendai-shi
Japan	Center Hospital of the National Center For Global Health and Medicine	Shinjuku-ku
Norway	Haukeland University Hospital	Bergen
Norway	Oslo Universitetssykehus	Oslo
Puerto Rico	Panoncology Trials Pan American Center For Oncology Trials, Llc	San Juan
Spain	Complejo Hospitalario Universitario A Coruna	A Coruña
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital General Universitario Vall D Hebron	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de La Paz	Madrid
Spain	Son Espases University Hospital	Palma de Mallorca
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Spain	Hospital Universitario Miguel Servet	Zaragoza
Sweden	Sahlgrenska University Hospital	Goteborg
Sweden	Skaenes Universitetssjukhus Lund	Lund
Sweden	Stockholm South General Hospital Sodersjukhuset	Stockholm
United Kingdom	Royal Sussex County Hospital	Brighton
United Kingdom	Addenbrooke'S Hospital	Cambridge
United Kingdom	Royal Surrey County Hospital	Guildford
United Kingdom	Castle Hill Hospital	Hull
United Kingdom	Leeds Teaching Hospital	Leeds
United Kingdom	Royal Free London Nhs Foundation Trust	London
United Kingdom	The Royal Marsden Nhs Foundation Trust - Chelsea	London
United Kingdom	The Christie Nhs Foundation Trust Uk	Manchester
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Royal Preston Hospital	Preston
United Kingdom	The Royal Marsden Nhs Foundation Trust - Sutton	Sutton
United Kingdom	Royal Cornwall Hospital Truro Sunrise Centre	Truro
United States	Virginia Cancer Specialists, Pc	Arlington	Virginia
United States	Texas Oncology	Austin	Texas
United States	Maryland Oncology Hematology, P.A.	Columbia	Maryland
United States	Baylor Scott and White Research Institute	Dallas	Texas
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	City of Hope National Medical Center	Duarte	California
United States	Ochsner Clinic	New Orleans	Louisiana
United States	Blue Ridge Cancer Care	Roanoke	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	Sansum Clinic	Santa Barbara	California
United States	Renovatio Clinical Consultants Llc	The Woodlands	Texas
United States	The University of Arizona Cancer Center	Tucson	Arizona
United States	Texas Oncology-Wichita Falls Texoma Cancer Center	Wichita Falls	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Denmark,  France,  Germany,  Italy,  Japan,  Norway,  Puerto Rico,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	Defined as the time from the date of randomization until disease progression according to RECIST v1.1 by BICR or death due to any cause.	up to 4.5 years
Secondary	Overall Survival (OS)	Defined as the time from the date of randomization until death due to any cause.	Up to 4.5 years
Secondary	Overall Response Rate (ORR)	Defined as the proportion of participants who have a confirmed complete response or partial response per RECIST v1.1 based on BICR.	Up to 4.5 years
Secondary	Duration of Response (DOR)	Defined as the time from the earliest date of documented response until earliest date of disease progression (per RECIST v1.1 based on BICR) or death from any cause, whichever comes first.	Up to 4.5 years
Secondary	Disease Control Rate(DCR)	Defined as the number of participants maintaining either an ORR or stable disease.	Up to 4.5 years
Secondary	Number of treatment-emergent adverse events	Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study treatment up to 90 days after last dose of study treatment.	Up to 4.5 years
Secondary	Cmax of retifanlimab when administered with chemotherapy	Maximum observed plasma or serum concentration.	Up to 4.5 years
Secondary	tmax of retifanlimab when administered with chemotherapy	Time to maximum concentration	Up to 4.5 years
Secondary	Cmin of retifanlimab when administered with chemotherapy	Minimum observed plasma or serum concentration over the dose interval	Up to 4.5 years
Secondary	AUC0-t of retifanlimab when administered with chemotherapy	Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t	Up to 4.5 years