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Trial record 1 of 1 for:    NCT04540211
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A Study of Atezolizumab Plus Tiragolumab in Combination With Paclitaxel and Cisplatin Compared With Paclitaxel and Cisplatin as First-Line Treatment in Participants With Unresectable Locally Advanced, Unresectable Recurrent, or Metastatic Esophageal Carcinoma (SKYSCRAPER-08)

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ClinicalTrials.gov Identifier: NCT04540211
Recruitment Status : Recruiting
First Posted : September 7, 2020
Last Update Posted : April 30, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:

The purpose of this study is to evaluate the efficacy and safety of atezolizumab plus tiragolumab in combination with paclitaxel and cisplatin (PC) compared with atezolizumab matching placebo plus tiragolumab matching placebo plus PC as first-line treatment in participants with unresectable locally advanced, unresectable recurrent, or metastatic esophageal carcinoma (EC). Participants will be randomized in a 1:1 ratio to receive one of the following treatment regimens during induction phase:

Arm A: Atezolizumab plus Tiragolumab and PC Arm B: Atezolizumab placebo plus Tiragolumab placebo and PC Following the induction phase, participants will continue maintenance therapy with either atezolizumab plus tiragolumab (Arm A) or atezolizumab matching placebo plus tiragolumab matching placebo (Arm B).


Condition or disease Intervention/treatment Phase
Esophageal Cancer Drug: Atezolizumab Drug: Tiragolumab Drug: Paclitaxel Drug: Cisplatin Drug: Atezolizumab Matching Placebo Drug: Tiragolumab Matching Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab Plus Tiragolumab in Combination With Paclitaxel and Cisplatin Compared With Paclitaxel and Cisplatin as First-Line Treatment in Patients With Unresectable Locally Advanced, Unresectable Recurrent, or Metastatic Esophageal Squamous Cell Carcinoma
Actual Study Start Date : October 30, 2020
Estimated Primary Completion Date : August 14, 2024
Estimated Study Completion Date : August 14, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Atezolizumab + Tiragolumab + PC
Participants will receive atezolizumab and tiragolumab on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase.
Drug: Atezolizumab
Atezolizumab at a fixed dose of 1200 milligrams (mg) administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Other Name: Tecentriq

Drug: Tiragolumab
Tiragolumab at a fixed dose of 600 mg administered by IV infusion every Q3W on Day 1 of each 21-day cycle.
Other Name: MTIG7192A

Drug: Paclitaxel
Paclitaxel 175 mg/m^2 administered by IV infusion on Day 1 of each 21-day cycle for 6 cycles.

Drug: Cisplatin
Cisplatin 60-80 mg/m^2 administered by IV infusion on Day 1 of each 21-day cycle for 6 cycles.

Placebo Comparator: Placebo + PC
Participants will receive atezolizumab matching placebo and tiragolumab matching placebo on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase.
Drug: Paclitaxel
Paclitaxel 175 mg/m^2 administered by IV infusion on Day 1 of each 21-day cycle for 6 cycles.

Drug: Cisplatin
Cisplatin 60-80 mg/m^2 administered by IV infusion on Day 1 of each 21-day cycle for 6 cycles.

Drug: Atezolizumab Matching Placebo
Atezolizumab matching placebo administered by IV infusion, Q3W on Day 1 of each 21-day cycle.

Drug: Tiragolumab Matching Placebo
Tiragolumab matching placebo administered by IV infusion, Q3W on Day 1 of each 21-day cycle.




Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: From randomization to death from any cause (up to approximately 35 months) ]
  2. Independent Review Facility (IRF)-Assessed Progression-Free Survival (PFS) [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 35 months) ]

Secondary Outcome Measures :
  1. Investigator-Assessed PFS [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 35 months) ]
  2. IRF-Assessed Confirmed Objective Response Rate (ORR) [ Time Frame: From randomization up to approximately 35 months ]
  3. Investigator-Assessed Confirmed ORR [ Time Frame: From randomization up to approximately 35 months ]
  4. IRF-Assessed Duration of Objective Response (DOR) [ Time Frame: From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 35 months) ]
  5. Investigator-Assessed DOR [ Time Frame: From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 35 months) ]
  6. Time to Confirmed Deterioration (TTCD) in Participant-Reported Physical Functioning, Role Functioning and Global Health Status (GHS)/Quality of Life (QoL) as Measured by EORTC QLQ-C30 [ Time Frame: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months) ]
    Clinically meaningful changes in physical functioning, role functioning, global health status (GHS)/QoL as measured by the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30). EORTC QLQ-C30 is a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) within the previous week. Functioning and symptoms items are scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. GHS and QoL items are scored on a 7-point scale: 1=Very poor, 2, 3, 4, 5, 6, 7=Excellent. Scores will be linearly transformed to a range of 0 to 100, with higher scores (i.e. closer to 100) reflecting better functioning, better GHS/QoL, and worse symptoms.

  7. TTCD in Participant-Reported Dysphagia as Measured by EORTC QLQ-OES18 [ Time Frame: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months) ]
    Clinically meaningful changes in dysphagia as measured by the EORTC Quality of Life-Esophageal Cancer, Module 18 Questionnaire (EORTC QLQ-OES18). EORTC QLQ-OES18 is a modular supplement to the EORTC QLQ-C30 questionnaire for use in participants with esophageal cancer. EORTC QLQ-OES18 consists of 4 multiple-item scale (dysphagia, eating, reflux, and pain) and 6 single items (trouble swallowing saliva, choked when swallowing, dry mouth, trouble with taste, trouble with coughing, and trouble talking) with a recall period of the previous week. Each symptom item is scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores will be linearly transformed to a range of 0 to 100, with higher transformed scores (i.e. closer to 100) reflecting worse symptoms.

  8. Percentage of Participants With Adverse Events (AEs) [ Time Frame: Up to approximately 35 months ]
  9. Minimum Serum Concentration (Cmin) of Tiragolumab [ Time Frame: Cycle 1 (cycle=21 days), Day 1: predose, 0.5 hour (h) postdose; Cycles 2, 3, 4, 8, 12, 16, Day 1: predose and at treatment discontinuation (TD) visit (up to approximately 35 months) ]
  10. Maximum Serum Concentration (Cmax) of Tiragolumab [ Time Frame: Cycle 1 (cycle=21 days), Day 1: predose, 0.5h postdose; Cycles 2, 3, 4, 8, 12, 16: Day 1: predose and at TD visit (up to approximately 35 months) ]
  11. Cmin of Atezolizumab [ Time Frame: Cycle 1 (cycle=21 days): Day 1 (predose, 0.5 h postdose); Cycles 2, 3, 4, 8, 12, 16: Day 1 (predose) and at TD visit (up to approximately 35 months) ]
  12. Cmax of Atezolizumab [ Time Frame: Cycle 1 (cycle=21 days): Day 1 (predose, 0.5 h postdose); Cycles 2, 3, 4, 8, 12, 16: Day 1 (predose) and at TD visit (up to approximately 35 months) ]
  13. Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab [ Time Frame: Predose on Day 1 of Cycles (cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 35 months) ]
  14. Percentage of Participants With ADAs to Atezolizumab [ Time Frame: Predose on Day 1 of Cycles (cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 35 months) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Histologically confirmed EC
  • Unresectable locally advanced, unresectable recurrent, or metastatic disease
  • Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Adequate hematologic and end-organ function
  • Female participants must be willing to avoid pregnancy and refrain from donating eggs during the treatment period and for 90 days after the final dose
  • Male participants with partners of childbearing potential must commit to the use of two methods of contraception and must not donate sperm for the study duration and 90 days after the final dose

Key Exclusion Criteria:

  • Palliative radiation treatment for EC within 4 weeks prior to initiation of study treatment
  • Evidence of complete esophageal obstruction not amenable to treatment
  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
  • Uncontrolled tumor-related pain, uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
  • Active or history of autoimmune disease or immune deficiency or leptomeningeal disease
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
  • Malignancies other than EC within 2 years prior to screening with a negligible risk of metastasis or death adequately treated with expected curative outcome
  • Severe infection within 4 weeks prior to initiation of study treatment or any active infection that, in the opinion of the investigator, could impact patient safety
  • Positive test result for human immunodeficiency virus (HIV)
  • Active hepatitis B or hepatitis C
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-CTLA-4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  • Treatment with any investigational therapy prior to initiation of study treatment
  • Poor peripheral venous access
  • Prior allogeneic stem cell or solid organ transplantation
  • Concurrent participation in another therapeutic clinical trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04540211


Contacts
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Contact: Reference Study ID Number: YO42138 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com

Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04540211    
Other Study ID Numbers: YO42138
First Posted: September 7, 2020    Key Record Dates
Last Update Posted: April 30, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Paclitaxel
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs