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SKYSCRAPER-08: 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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04540211
Collaborator
(none)
450
Enrollment
69
Locations
2
Arms
57.5
Anticipated Duration (Months)
6.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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
Phase 3

Study Design

Study Type:
Interventional
Anticipated 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 :
Oct 30, 2020
Anticipated Primary Completion Date :
Aug 14, 2024
Anticipated Study Completion Date :
Aug 14, 2025

Arms and Interventions

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 Names:
  • 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 Names:
  • 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.

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival (OS) [From randomization to death from any cause (up to approximately 35 months)]

    2. Independent Review Facility (IRF)-Assessed Progression-Free Survival (PFS) [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 [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) [From randomization up to approximately 35 months]

    3. Investigator-Assessed Confirmed ORR [From randomization up to approximately 35 months]

    4. IRF-Assessed Duration of Objective Response (DOR) [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 [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 [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 [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) [Up to approximately 35 months]

    9. Minimum Serum Concentration (Cmin) of Tiragolumab [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 [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 [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 [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 [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 [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)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Anyang Tumor Hosptial Anyang City China 455000
    2 Beijing Luhe Hospital Capital Medical University Beijing City China 101100
    3 Beijing Cancer Hospital Beijing China 100142
    4 the First Hospital of Jilin University Changchun China 130021
    5 Jilin Cancer Hospital Changchun China 132013
    6 Hunan Cancer Hospital Changsha City China 410013
    7 Affiliated Hospital of Chengde Medical University Chengde City China 067020
    8 Sichuan Provincial Cancer Hospital Chengdu China 610041
    9 West China Hospital, Sichuan University Chengdu China 610041
    10 Chongqing Sanxia Central Hospital Chongqing City China 404000
    11 The First People's Hospital of Foshan Foshan China 510000
    12 Fujian Provincial Hospital Fuzhou City China 350001
    13 Fujian Cancer Hospital Fuzhou China 350014
    14 Southern Medical University Nanfang Hospital Guangdong Province Guangzhou City China 510515
    15 Harbin Medical University Cancer Hospital Harbin China 150081
    16 Anhui Province Cancer Hospital Hefei China 230000
    17 Anhui Provincial Hospital Hefei China 230001
    18 The Second Affiliated Hospital of Anhui Medical University Hefei China 230601
    19 Huai'an First People's Hospital Huai'an City China 223300
    20 The Second People's Hospital of Huai'an Huai'an City China 223300
    21 Affiliated Hopsital of Jining Medical University Jining China 272000
    22 Gansu Province People Hospital Lanzhou China 730000
    23 The First People's Hospital of Lian Yun Gang Lianyungang China 222023
    24 Linyishi Cancer Hospital Linyi City China 276034
    25 The First Affiliated Hospital to Henan University of Science and Technology Luoyang China 471003
    26 Jiangsu Province Hospital of Chinese Medicine Nanjing City China 210029
    27 Jiangsu Cancer Hospital Nanjing City China 211100
    28 Nan Tong Tumor Hospital Nantong City China 226361
    29 Fudan University Shanghai Cancer Center Shanghai City China 200120
    30 Shanghai Chest Hospital Shanghai China 200000
    31 Zhongshan Hospital Fudan University Shanghai China 200032
    32 Cancer Hospital of Shantou University Medical College Shantou China 515041
    33 Liaoning Provincial Cancer Hospital Shengyang China 110042
    34 The University of Hong Kong-Shenzhen Hospital Shenzhen City China 518053
    35 Suining Central Hospital Suining China 629000
    36 Tianjin Cancer Hospital Tianjin China 300060
    37 Weifang People's Hospital Weifang City China 261041
    38 Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology Wuhan City China 430022
    39 Hubei Cancer Hospital Wuhan China 430079
    40 Affiliated Hospital of Jiangnan University(Wuxi Fourth People's Hospital ) Wuxi City China 214062
    41 The Second Affiliated Hospital of The Fourth Military Medical University (Tangdu Hospital) Xi'an China 710038
    42 First Affiliated Hospital of Medical College of Xi'an Jiaotong University Xi'an China 710061
    43 The First Affiliated Hospital of Xiamen University Xiamen China 361003
    44 Zhongshan Hospital Xiamen University Xiamen China 361004
    45 Xiangyang Central Hospital Xiangyang China
    46 The First Affiliated Hospital of Xinxiang Medical University Xinxiang City China 453000
    47 Xuzhou Central Hospital Xuzhou China 221000
    48 Northern Jangsu People's Hospital Yangzhou City China 225001
    49 Zhejiang Cancer Hospital Zhejiang China 310022
    50 Henan Cancer Hospital Zhengzhou China 450008
    51 The First Affiliated Hospital of Zhengzhou University Zhengzhou China 450052
    52 Queen Mary Hospital; Dept. of Clinical Oncology Hong Kong Hong Kong
    53 Prince of Wales Hosp; Dept. Of Clinical Onc Shatin Hong Kong
    54 Kyungpook National University Chilgok Hospital Daegu Korea, Republic of 41404
    55 National Cancer Center Goyang-si Korea, Republic of 10408
    56 Seoul National University Bundang Hospital Seongnam-si Korea, Republic of 13605
    57 Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 03722
    58 Asan Medical Center Seoul Korea, Republic of 05505
    59 Samsung Medical Center Seoul Korea, Republic of 06351
    60 Korea University Guro Hospital Seoul Korea, Republic of 08308
    61 Chang Gung Medical Foundation - Kaohsiung; Oncology Kaohisung Taiwan 833
    62 National Cheng Kung University Hospital; Oncology Tainan Taiwan 00704
    63 Taipei Veterans General Hospital; Department of Oncology Taipei City Taiwan 112201
    64 National Taiwan University Hospital; Oncology Zhongzheng Dist. Taiwan 10048
    65 Chulalongkorn Hospital; Medical Oncology Bangkok Thailand 10330
    66 Rajavithi Hospital; Division of Medical Oncology Bangkok Thailand 10400
    67 Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc Bangkok Thailand 10400
    68 Siriraj Hospital; Medical Oncology Unit Bangkok Thailand 10700
    69 Songklanagarind Hospital; Department of Oncology Songkhla Thailand 90110

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT04540211
    Other Study ID Numbers:
    • YO42138
    First Posted:
    Sep 7, 2020
    Last Update Posted:
    Aug 4, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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:
    Paclitaxel
    Atezolizumab
    Antibodies, Monoclonal

    Study Results

    No Results Posted as of Aug 4, 2022