HumRes52393
|
SNCTP000004660
|
BASEC2020-01826
|
NCT04543617
A study to investigate the safety and efficacy of Atezolizumab and Tiragolumab compared to a placebo treatment in patients with inoperable esophageal cancer
Zusammenfassung der Studie
This is a study to assess the efficacy of Tiragolumab and Tecentriq® (Atezolizumab) compared to a placebo treatment in patients with locally advanced esophageal cancer. Approximately 750 patients will participate in this study worldwide. The study will last approximately 4 years. In this study, patients will be assigned to three treatment groups and will receive either Tiragolumab plus Tecentriq®, placebo plus Tecentriq®, or a double placebo. The group assignment will be determined randomly (like flipping a coin). The probability of being assigned to one of the groups is equal. Neither the patient nor the investigator can choose or know the group.
(BASEC)
Untersuchte Intervention
Patients will receive treatment in 21-day cycles, as described below:
Tecentriq® plus Tiragolumab group
Tecentriq®: i.v. (intravenous) infusion over 30-60 minutes on Day 1 of each cycle
Tiragolumab: i.v. infusion over 30-60 minutes on Day 1 of each cycle
Tecentriq® plus placebo group
Tecentriq®: i.v. infusion over 30-60 minutes on Day 1 of each cycle
Placebo matching Tiragolumab: i.v. infusion over 30-60 minutes on Day 1 of each cycle
Double placebo group
Placebo matching Tecentriq®: i.v. infusion over 30-60 minutes on Day 1 of each cycle
Placebo matching Tiragolumab: i.v. infusion over 30-60 minutes on Day 1 of each cycle
(BASEC)
Untersuchte Krankheit(en)
Esophageal cancer
(BASEC)
Kriterien zur Teilnahme
Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the esophagus ECOG performance status of 0 or 1 Stage II-IVA according to the American Joint Committee on Cancer/Union for International Cancer Control, 8th edition, inoperable locally advanced disease (medical or surgical treatment declined) Patients with stage IVB, where a cervical or upper thoracic squamous cell carcinoma of the esophagus with exclusively supraclavicular lymph node metastases has been diagnosed and who, in the opinion of the treating physician, the multidisciplinary team, or the tumor board, are eligible for definitive chemoradiotherapy, are eligible for participation. Definitive concurrent chemoradiotherapy according to regional oncological guidelines for esophageal cancer with the following criteria: Patients with unresectable tumors must have received at least two cycles of platinum-based chemotherapy and radiotherapy that align with the definitive treatment (50-64 Gy), without evidence of radiological disease progression according to RECIST v1.1, as documented by comparison of scans (pre- and post-definitive chemoradiotherapy) before study initiation. Patients with cervical squamous cell carcinoma of the esophagus may receive a higher radiation dose (50-66 Gy), according to local oncological guidelines. Inclusion in the study must occur within 1-84 days after the last dose of definitive chemoradiotherapy. Archived tumor samples collected prior to the start of definitive chemoradiotherapy in paraffin blocks (preferably) or ≥15 unstained slides with freshly cut, serial sections Patients whose tumor tissue is not evaluable for PD-L1 expression are not eligible for the study. Patients with detectable Hepatitis B surface antigen (HBsAg) or detectable HBV DNA should be treated according to treatment guidelines. Patients receiving antiviral medication must have started treatment at least 2 weeks prior to inclusion in the study and should continue treatment for at least 6 months after the last dose of study treatment. (BASEC)
Ausschlusskriterien
Previous treatment with antibodies (these are molecules released into the blood). The special feature of antibodies is that each antibody has a specific target. For example, certain antibodies of the CD137 agonist class or immune checkpoint inhibitor therapies, including therapeutic anti-CTLA-4, -PD-1, -PD, target specific proteins on the surface of tumor cells. Any persistent adverse effect (grade >=2) from previous chemoradiotherapy. Patients with irreversible or manageable hearing loss may be eligible. Evidence of complete esophageal obstruction (the hollow tube that runs from the throat to the stomach may be narrowed or completely blocked) that cannot be easily treated. Histology (a microscopic examination of tissue) shows a type of small cell cancer of the esophagus. High risk for the development of an esophageal fistula according to clinical assessment or imaging, such as a history or symptoms of an esophageal fistula or tumor invasion into major vessels or the trachea (the trachea is the tubular organ that connects the larynx to the two main bronchi). Previous surgical removal of the esophagus Positive Epstein-Barr virus (EBV) viral capsid antigen IgM test at screening History of other malignancies (malignant cancers) other than esophageal cancer within 2 years prior to screening. Exceptions are malignancies with negligible risk of metastasis or death (e.g., 5-year survival rate > 90%), such as adequately treated cervical cancer, clear cell skin cancer, localized prostate cancer, ductal carcinoma in situ (a pathological proliferation of cells in the milk ducts of the female breast) or early-stage uterine cancer. (BASEC)
Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the esophagus ECOG performance status of 0 or 1 Stage II-IVA according to the American Joint Committee on Cancer/Union for International Cancer Control, 8th edition, inoperable locally advanced disease (medical or surgical treatment declined) Patients with stage IVB, where a cervical or upper thoracic squamous cell carcinoma of the esophagus with exclusively supraclavicular lymph node metastases has been diagnosed and who, in the opinion of the treating physician, the multidisciplinary team, or the tumor board, are eligible for definitive chemoradiotherapy, are eligible for participation. Definitive concurrent chemoradiotherapy according to regional oncological guidelines for esophageal cancer with the following criteria: Patients with unresectable tumors must have received at least two cycles of platinum-based chemotherapy and radiotherapy that align with the definitive treatment (50-64 Gy), without evidence of radiological disease progression according to RECIST v1.1, as documented by comparison of scans (pre- and post-definitive chemoradiotherapy) before study initiation. Patients with cervical squamous cell carcinoma of the esophagus may receive a higher radiation dose (50-66 Gy), according to local oncological guidelines. Inclusion in the study must occur within 1-84 days after the last dose of definitive chemoradiotherapy. Archived tumor samples collected prior to the start of definitive chemoradiotherapy in paraffin blocks (preferably) or ≥15 unstained slides with freshly cut, serial sections Patients whose tumor tissue is not evaluable for PD-L1 expression are not eligible for the study. Patients with detectable Hepatitis B surface antigen (HBsAg) or detectable HBV DNA should be treated according to treatment guidelines. Patients receiving antiviral medication must have started treatment at least 2 weeks prior to inclusion in the study and should continue treatment for at least 6 months after the last dose of study treatment. (BASEC)
Ausschlusskriterien
Previous treatment with antibodies (these are molecules released into the blood). The special feature of antibodies is that each antibody has a specific target. For example, certain antibodies of the CD137 agonist class or immune checkpoint inhibitor therapies, including therapeutic anti-CTLA-4, -PD-1, -PD, target specific proteins on the surface of tumor cells. Any persistent adverse effect (grade >=2) from previous chemoradiotherapy. Patients with irreversible or manageable hearing loss may be eligible. Evidence of complete esophageal obstruction (the hollow tube that runs from the throat to the stomach may be narrowed or completely blocked) that cannot be easily treated. Histology (a microscopic examination of tissue) shows a type of small cell cancer of the esophagus. High risk for the development of an esophageal fistula according to clinical assessment or imaging, such as a history or symptoms of an esophageal fistula or tumor invasion into major vessels or the trachea (the trachea is the tubular organ that connects the larynx to the two main bronchi). Previous surgical removal of the esophagus Positive Epstein-Barr virus (EBV) viral capsid antigen IgM test at screening History of other malignancies (malignant cancers) other than esophageal cancer within 2 years prior to screening. Exceptions are malignancies with negligible risk of metastasis or death (e.g., 5-year survival rate > 90%), such as adequately treated cervical cancer, clear cell skin cancer, localized prostate cancer, ductal carcinoma in situ (a pathological proliferation of cells in the milk ducts of the female breast) or early-stage uterine cancer. (BASEC)
Studienstandort
Bern, Zürich
(BASEC)
Argentina, Australia, Austria, Belgium, Brazil, China, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Kenya, Korea, Republic of, Morocco, New Zealand, Poland, Portugal, Russian Federation, South Africa, Spain, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States (ICTRP)
Sponsor
NA
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Annina Williner
+41 61 715 43 55
switzerland.clinical-research@clutterroche.comRoche Pharma (Schweiz) AG
(BASEC)
Allgemeine Auskünfte
Hoffmann-La Roche
(ICTRP)
Wissenschaftliche Auskünfte
Hoffmann-La Roche
(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Bern
(BASEC)
Datum der Bewilligung durch die Ethikkommission
11.01.2021
(BASEC)
ICTRP Studien-ID
NCT04543617 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF ATEZOLIZUMAB WITH OR WITHOUT TIRAGOLUMAB (ANTI-TIGIT ANTIBODY) IN PATIENTS WITH UNRESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA WHOSE CANCERS HAVE NOT PROGRESSED FOLLOWING DEFINITIVE CONCURRENT CHEMORADIOTHERAPY (BASEC)
Wissenschaftlicher Titel
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab With or Without Tiragolumab (Anti-TIGIT Antibody) in Patients With Unresectable Esophageal Squamous Cell Carcinoma Whose Cancers Have Not Progressed Following Definitive Concurrent Chemoradiotherapy (ICTRP)
Öffentlicher Titel
A Study of Atezolizumab With or Without Tiragolumab in Participants With Unresectable Esophageal Squamous Cell Carcinoma Whose Cancers Have Not Progressed Following Definitive Concurrent Chemoradiotherapy (ICTRP)
Untersuchte Krankheit(en)
Esophageal Squamous Cell Carcinoma (ICTRP)
Untersuchte Intervention
Drug: TiragolumabDrug: AtezolizumabDrug: Tiragolumab Matching PlaceboDrug: Atezolizumab Matching Placebo (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Ein-/Ausschlusskriterien
Key Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of
the esophagus
- Unresectable disease ineligible for curative surgery based on the documented opinion
of the qualified medical, surgical or radiation oncologist prior to dCRT and is not
expected to undergo tumor resection during the course of the study
- dCRT treatment according to regional oncology guidelines for esophageal cancer
- Representative archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens
collected prior to initiation of dCRT
- Adequate hematologic and end-organ function prior to randomization
- Women of childbearing potential must remain abstinent or use contraceptive methods
with a failure rate of < 1% per year during the treatment period, for 5 months after
the final dose of atezolizumab/placebo, and for 90 days after the final dose of
tiragolumab/placebo, whichever is later
- Men must agree to remain abstinent (refrain from heterosexual intercourse) or use a
condom, and agree to refrain from donating sperm during the treatment period and for
90 days after the final dose of tiragolumab/placebo.
Key Exclusion Criteria:
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies,
including anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-TIGIT therapeutic antibodies
- Any unresolved toxicity of National Cancer Institute's (NCI) Common Terminology
Criteria for Adverse Events (CTCAE) Grade = 2 from the prior chemoradiation therapy
with the exception of irreversible and manageable hearing loss
- Prior allogeneic stem cell or solid organ transplantation
- Active or history of autoimmune disease or immune deficiency
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis
- Malignancies other than esophageal cancer within 2 years prior to screening, with
the exception of malignancies with a negligible risk of metastasis or death
- Treatment with any other investigational agent, including epidermal growth factor
receptor (EGFR) inhibitors, with therapeutic intent for esophageal cancer prior to
randomization. (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Arm A vs Arm C: Investigator-Assessed Progression-Free Survival (PFS);Arm A vs Arm C: Overall Survival (OS);Arm B vs Arm C: OS (ICTRP)
Arm B vs Arm C: Investigator-Assessed PFS;Arm A vs Arm B: Investigator-Assessed PFS;Arm A vs Arm B: OS;Independent Review Facility (IRF)-Assessed PFS;Investigator-Assessed Confirmed Objective Response Rate (ORR);IRF-Assessed Confirmed ORR;Investigator-Assessed Duration of Objective Response (DOR);IRF-Assessed DOR;Percentage of Participants With Clinically Meaningful Changes in Physical Functioning, Role Functioning, Quality of Life (QoL) as Measured by EORTC QLQ-C30;Percentage of Participants With Clinically Meaningful Changes in Dysphagia as Measured by EORTC QLQ-OES18;Percentage of Participants With Adverse Events (AEs);Serum Concentration of Tiragolumab;Serum Concentration of Atezolizumab;Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab;Percentage of Participants With ADAs to Atezolizumab (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Clinical Trial, Hoffmann-La Roche (ICTRP)
Sekundäre IDs
2020-001178-31, YO42137 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT04543617 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar