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Investigating the Effects of Atezolizumab in People Whose Tumour DNA or RNA Indicates Possible Sensitivity (CAPTIV-8)

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ClinicalTrials.gov Identifier: NCT04273061
Recruitment Status : Recruiting
First Posted : February 17, 2020
Last Update Posted : July 14, 2021
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
British Columbia Cancer Agency

Brief Summary:

This study will investigate the effects of atezolizumab on select cancer types in people whose analysis of tumour DNA and RNA indicates they may be sensitive to atezolizumab. This study aims to determine if the information from the cancer genome analysis corresponds with the effects of atezolizumab on individuals and their cancer.

This is a Phase 2 study, which is undertaken after preliminary safety testing on a drug is completed, and will involve approximately 200 participants. Participants are assigned to one of 8 cohorts based on their primary tumour type: breast, lung, gastrointestinal (GI), primary unknown, genitourinary (GU), sarcoma, gynecological, and 'other' cancer types. Participants in all cohorts will receive the same dose of atezolizumab (1200 mg every 3 weeks). In the first stage for each cohort, 8 participants will be enrolled and if no participants respond to treatment, enrollment to that cohort will be closed. If 1 or more participants respond to treatment, up to 16 additional participants will be enrolled to that cohort. Participants continue on treatment until they no longer may benefit from the treatment or they decide to stop treatment.


Condition or disease Intervention/treatment Phase
Breast Cancer Lung Cancer Gastrointestinal Cancer Genitourinary Cancer Gynecologic Cancer Sarcoma Unknown Primary Tumors Head and Neck Cancer Skin Cancer Drug: Atezolizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Simon 2-stage design; 8 tumour-defined cohorts consisting of 8 to 24 participants each.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Canadian Atezolizumab Precision Targeting for Immunotherapy Intervention
Actual Study Start Date : June 17, 2020
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Breast Cohort
Cohort of participants whose primary tumour type is breast.
Drug: Atezolizumab
1200 mg by intravenous infusion every 3 weeks as tolerated
Other Name: TECENTRIQ

Experimental: Lung Cohort
Cohort of participants whose primary tumour type is lung.
Drug: Atezolizumab
1200 mg by intravenous infusion every 3 weeks as tolerated
Other Name: TECENTRIQ

Experimental: GI Cohort
Cohort of participants whose primary tumour type is gastrointestinal (including pancreas and hepatobiliary).
Drug: Atezolizumab
1200 mg by intravenous infusion every 3 weeks as tolerated
Other Name: TECENTRIQ

Experimental: GU Cohort
Cohort of participants whose primary tumour type is genitourinary.
Drug: Atezolizumab
1200 mg by intravenous infusion every 3 weeks as tolerated
Other Name: TECENTRIQ

Experimental: Gyne Cohort
Cohort of participants whose primary tumour type is gynecological.
Drug: Atezolizumab
1200 mg by intravenous infusion every 3 weeks as tolerated
Other Name: TECENTRIQ

Experimental: Sarcoma Cohort
Cohort of participants whose primary tumour type is sarcoma.
Drug: Atezolizumab
1200 mg by intravenous infusion every 3 weeks as tolerated
Other Name: TECENTRIQ

Experimental: Primary Unknown Cohort
Cohort of participants whose primary tumour type is unknown.
Drug: Atezolizumab
1200 mg by intravenous infusion every 3 weeks as tolerated
Other Name: TECENTRIQ

Experimental: Other Cohort
Cohort of participants whose primary tumour type is not classified as one of the other study arms. This cohort includes participants with cancers from the head and neck, skin, or rare cancers.
Drug: Atezolizumab
1200 mg by intravenous infusion every 3 weeks as tolerated
Other Name: TECENTRIQ




Primary Outcome Measures :
  1. Overall response rate (ORR) in each tumour-defined cohort, as defined by RECIST 1.1 [ Time Frame: From the date of the screening scan (within 28 days of first dose) until the date of confirmed progression, withdrawal, or date of death, whichever comes first, assessed up to 54 months. ]
    The proportion of participants in each tumour-defined cohort who have a complete response (CR) or partial response (PR) to treatment, as defined by RECIST 1.1.


Secondary Outcome Measures :
  1. Progression-free survival (PFS) in each tumour-defined cohort from the initiation of atezolizumab [ Time Frame: From the date of first dose until the date of confirmed progression, withdrawal, or date of death, whichever comes first, assessed up to 54 months. ]
    The length of time from the first dose of atezolizumab until participants in each tumour-defined cohort have progressive disease (PD), as defined by RECIST 1.1.

  2. Clinical benefit rate (CBR) in each tumour-defined cohort at the 18-week follow-up scan [ Time Frame: From the date of the screening scan (within 28 days of first dose) until the date of the 18-week follow-up scan. ]
    The percentage of participants in each tumour-defined cohort who have a complete response (CR), partial response (PR), or stable disease (SD) response to treatment, as defined by RECIST 1.1, at the 18-week follow-up scan.

  3. Overall survival (OS) in each tumour-defined cohort from the initiation of atezolizumab [ Time Frame: From the date of first dose until the date of death, assessed up to 54 months. ]
    The length of time from the initiation of atezolizumab that participants in each tumour-defined cohort survive.

  4. Quality-adjusted survival in each tumour-defined cohort from the initiation of atezolizumab [ Time Frame: From the date of first dose until the treatment discontinuation visit (within 30 days of last dose), withdrawal, or date of death, whichever comes first, assessed up to 54 months. ]
    Survival time (from the initiation of atezolizumab) multiplied by quality of life. Participants' responses to health-related quality of life questions on the EQ-5D-3L questionnaire will be converted to utility weights using existing conversion scales that are based on patient and public valuations of the health states described by the EQ-5D-3L questionnaire.

  5. Duration of response (DoR) in each tumour-defined cohort [ Time Frame: From the date of the scan that shows the first response to treatment until the date of progression, withdrawal, or date of death, whichever comes first, assessed up to 54 months. ]
    The length of time from the first response to treatment (CR or PR) until participants in each tumour-defined cohort have progressive disease (PD), as defined by RECIST 1.1.


Other Outcome Measures:
  1. Putative markers of sensitivity to atezolizumab in each tumour-defined cohort [ Time Frame: From the date of screening sample collection until the date of progression, withdrawal, or date of death, whichever comes first, assessed up to 54 months. ]
    From blood and tissue samples collected throughout the study, identify putative markers of sensitivity to atezolizumab based on the response to treatment of the participants in each tumour-defined cohort.

  2. Putative primary and secondary resistance markers to atezolizumab in each tumour-defined cohort [ Time Frame: From the date of screening sample collection until the date of progression, withdrawal, or date of death, whichever comes first, assessed up to 54 months. ]
    From blood and tissue samples collected throughout the study, identify putative primary and secondary resistance markers to atezolizumab based on the response to treatment of the participants in each tumour-defined cohort.

  3. Putative germline predictors of adverse events or toxicities of interest in each tumour-defined cohort [ Time Frame: From the date of screening sample collection until the date of progression, withdrawal, or date of death, whichever comes first, assessed up to 54 months. ]
    From blood and tissue samples collected throughout the study, identify putative germline predictors of adverse events or toxicities of interest to atezolizumab based on the response to treatment of the participants in each tumour-defined cohort.

  4. Compare the utility of iRECIST for response assessment to RECIST 1.1 in each tumour-defined cohort [ Time Frame: From the date of the screening scan (within 28 days of first dose) until the date of progression, withdrawal, or date of death, whichever comes first, assessed up to 54 months. ]
    Participant response to treatment as per RECIST 1.1. compared to the response to treatment as per the modified response evaluation criteria in solid tumours for immunotherapy trials (iRECIST) from screening until progression in each tumour-defined cohort.



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

Inclusion Criteria:

  • Age greater than or equal to 18 years at the time of signature of informed consent.
  • Participants with an incurable solid tumour who have undergone whole genome and transcriptome analysis (WGTA) as part of Personalized OncoGenomics (POG) or equivalent program.

    a. Participants must have had successful sequencing of their tumour, been formally reviewed by the POG genome analysts and found to have CAPTIV-8 factors identified (including Immune, Burden, Variant (IBV) score ≥ 5), been reviewed at the Molecular Tumour Board (MTB), and allocated to a specific tumour-defined cohort (that is open for enrolment) with a final opinion documented.

  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  • Participants must have measurable disease, as defined by RECIST 1.1.
  • Life expectancy of at least 12 weeks.
  • Adequate hematologic and end-organ function, as defined by the following laboratory results obtained within 28 days prior to the first study treatment:

    1. Absolute neutrophil count (ANC) ≥ 1500 cells/µL without granulocyte colony- stimulating factor support.
    2. White blood cell (WBC) counts > 2500/µL.
    3. Lymphocyte count ≥ 500/µL.
    4. Serum albumin ≥ 2.5 g/dL.
    5. Platelet count ≥ 100,000/µL without transfusion (without transfusion within 2 weeks of laboratory test used to determine eligibility).
    6. Hemoglobin ≥ 9.0 g/dL, participants may be transfused or receive erythropoietic treatment to meet this criterion.
    7. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 × Upper Limit of Normal (ULN). This applies only to participants who are not receiving therapeutic anticoagulation; participants receiving therapeutic anticoagulation must have an INR or aPTT within therapeutic limits for at least 1 week prior to enrolment.
    8. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 × ULN with the following exceptions: i) Participants with documented liver metastases: AST and/or ALT ≤ 5 × ULN. ii) Participants with documented liver or bone metastases: ALP ≤ 5 × ULN.
    9. Serum bilirubin ≤ 1.5 × ULN. Participants with known Gilbert's syndrome who have serum bilirubin level ≤ 3 × ULN may be enrolled.
    10. Serum creatinine ≤ 1.5 × ULN.
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than 1% (one percent) per year during the treatment period and for at least 5 months after the last dose of atezolizumab.
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse with a female partner of childbearing potential or who is pregnant) or use contraceptive measures that result in a failure rate of less than 1% (one percent) per year, and agreement to refrain from donating sperm, during the treatment period and for at least 5 months after the last dose of atezolizumab.
  • Ability to give informed consent for the study procedures defined in this protocol.

Exclusion Criteria:

  • Any prior treatment with monoclonal antibodies targeting the Programmed Death 1/Ligand (PD-1/PD-L1) axis, including antibody-drug conjugates and other experimental agents.
  • Treatment with any approved or investigational agent or participation in another clinical trial with therapeutic intent within 14 days or five half-lives of the drug, whichever is longer, prior to enrollment.
  • Asymptomatic participants with treated or untreated central nervous system (CNS) lesions are eligible provided that all of the following criteria are met:

    1. Measurable disease, per RECIST v1.1, must be present outside the CNS.
    2. The participant has no history of intracranial hemorrhage or spinal cord hemorrhage.
    3. The participant has not undergone stereotactic radiotherapy within 7 days prior to the initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment.
    4. The participants has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted.
  • Pregnancy or breastfeeding.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation.
  • Active autoimmune disease at any point within the last 2 years prior to enrollment including but not limited to:

    1. Myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
    2. Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone may be eligible for this study.
    3. Participants with controlled Type I diabetes mellitus on a stable dose of insulin regimen are eligible for this study.
  • Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., participants with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:

    1. Rash must cover less than 10% (ten percent) of body surface area (BSA).
    2. Disease is well controlled at baseline and only requiring low potency topical steroids.
    3. No acute exacerbations of underlying condition within the last 12 months requiring treatment with either psoralen plus ultraviolet radiation (PUVA), methotrexate, retinoids, biologic agents, oral calcineurin inhibitors or high potency or oral steroids.
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Previous positive test for HIV (participants with a past history of/or symptoms of HIV are eligible only if serological tests are negative).
  • Participants with known active hepatitis B virus (HBV; chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C.
  • Active tuberculosis.
  • Severe infections within 2 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina.
  • Major surgical procedure within 21 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study.
  • Prior allogeneic stem cell or solid organ transplant.
  • Treatment with systemic immunostimulatory agents (including but not limited to interferons, interleukin-2 (IL-2)) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1.
  • Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumour necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial.
  • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab.
  • Participants who are otherwise felt by the treating clinician to be unfit to proceed with this protocol.

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): NCT04273061


Contacts
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Contact: Janessa Laskin, MD 604-877-6000 ext 672617 jlaskin@bccancer.bc.ca
Contact: Daniel Renouf, MD, MPH 604-877-6000 ext 672445 drenouf@bccancer.bc.ca

Locations
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Canada, British Columbia
BC Cancer Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Janessa Laskin, MD    604-877-6000 ext 672617    jlaskin@bccancer.bc.ca   
Principal Investigator: Janessa Laskin, MD         
Sub-Investigator: Daniel J Renouf, MD, MPH         
Sponsors and Collaborators
British Columbia Cancer Agency
Hoffmann-La Roche
Investigators
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Principal Investigator: Janessa Laskin, MD BC Cancer
Publications:
Balachandran VP, Łuksza M, Zhao JN, Makarov V, Moral JA, Remark R, Herbst B, Askan G, Bhanot U, Senbabaoglu Y, Wells DK, Cary CIO, Grbovic-Huezo O, Attiyeh M, Medina B, Zhang J, Loo J, Saglimbeni J, Abu-Akeel M, Zappasodi R, Riaz N, Smoragiewicz M, Kelley ZL, Basturk O; Australian Pancreatic Cancer Genome Initiative; Garvan Institute of Medical Research; Prince of Wales Hospital; Royal North Shore Hospital; University of Glasgow; St Vincent's Hospital; QIMR Berghofer Medical Research Institute; University of Melbourne, Centre for Cancer Research; University of Queensland, Institute for Molecular Bioscience; Bankstown Hospital; Liverpool Hospital; Royal Prince Alfred Hospital, Chris O'Brien Lifehouse; Westmead Hospital; Fremantle Hospital; St John of God Healthcare; Royal Adelaide Hospital; Flinders Medical Centre; Envoi Pathology; Princess Alexandria Hospital; Austin Hospital; Johns Hopkins Medical Institutes; ARC-Net Centre for Applied Research on Cancer, Gönen M, Levine AJ, Allen PJ, Fearon DT, Merad M, Gnjatic S, Iacobuzio-Donahue CA, Wolchok JD, DeMatteo RP, Chan TA, Greenbaum BD, Merghoub T, Leach SD. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature. 2017 Nov 23;551(7681):512-516. doi: 10.1038/nature24462. Epub 2017 Nov 8.

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Responsible Party: British Columbia Cancer Agency
ClinicalTrials.gov Identifier: NCT04273061    
Other Study ID Numbers: H19-04010
First Posted: February 17, 2020    Key Record Dates
Last Update Posted: July 14, 2021
Last Verified: July 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by British Columbia Cancer Agency:
Genomic analysis
Atezolizumab
Whole genome and transcriptome analysis
Immune Burden Variant score
Immune checkpoint inhibition
Personalized OncoGenomics
Phase 2
Precision targeting
Additional relevant MeSH terms:
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Skin Neoplasms
Gastrointestinal Neoplasms
Urogenital Neoplasms
Neoplasms, Unknown Primary
Neoplasms
Neoplasms by Site
Skin Diseases
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Atezolizumab
Antineoplastic Agents