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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04929223




Registration number
NCT04929223
Ethics application status
Date submitted
11/06/2021
Date registered
18/06/2021

Titles & IDs
Public title
A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)
Scientific title
A Phase I/Ib Global, Multicenter, Open-label Umbrella Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)
Secondary ID [1] 0 0
WO42758
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Inavolisib
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Cetuximab
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Tiragolumab
Treatment: Drugs - SY-5609
Treatment: Drugs - Divarasib
Treatment: Drugs - FOLFOX
Treatment: Drugs - FOLFIRI

Experimental: Inavolisib + Cetuximab - Participants will receive 9 milligrams (mg) of inavolisib by mouth once daily (QD) on Days 8-28 of Cycle 1, then QD on Days 1-28 from Cycle 2 onwards (1 cycle=28 days).

Participants will also receive cetuximab intravenous (IV) infusion 400 mg/m2 body surface area on Day 1 of Cycle 1. All subsequent weekly (QW) doses will be 250 mg/m2 each.

Experimental: Inavolisib + Bevacizumab - Participants will receive 9 mg of inavolisib by mouth QD combined with bevacizumab 15 milligram/kilogram (mg/kg) IV once every three weeks (Q3W) on Day 1 of each cycle (1 cycle=21 days).

Experimental: Atezolizumab + Tiragolumab + Bevacizumab - Participants in this randomized cohort will receive 1200 mg of atezolizumab by IV infusion on Day 1 of each cycle, combined with tiragolumab at a dose of 600 mg IV infusion on Day 1 of each cycle and bevacizumab IV infusion at a dose of 15 mg/kg on Day 1 of each cycle. (Cycle length=21 days)

Experimental: Atezolizumab + Tiragolumab - Participants in this randomized cohort will receive 1200 mg of atezolizumab by IV infusion on Day 1 of each cycle combined with tiragolumab 600 mg IV infusion on Day 1 of each cycle. (Cycle length=21 days)

Experimental: Atezolizumab + SY-5609 - Participants will receive 1680 mg of atezolizumab by IV infusion on Day 1 of each cycle Q4W in repeated 28-day cycles combined with SY-5609 at a dose of 3, 4, 5, 6, 7 or 10 mg by mouth for 7 days, followed by 7 days off. (Cycle length=28 days) Open in the United States only.

Experimental: Divarasib + Cetuximab + FOLFOX - Participants will receive cetuximab IV 500 mg/m2 body surface area on Days 1 and 15 and FOLFOX on Days 1 and 15 with divarasib PO QD on Days 1-28. (Cycle length=28 days)

Experimental: Divarasib + Cetuximab - Participants will receive cetuximab IV 500 mg/m2 body surface area on Days 1 and 15 with divarasib PO QD on Days 1-28. (Cycle length=28 days)

Experimental: Divarasib + Cetuximab + FOLFIRI - Participants will receive cetuximab IV 500 mg/m2 body surface area on Days 1 and 15 and FOLFIRI on Days 1 and 15 with divarasib PO QD on Days 1-28. (Cycle length=28 days)


Treatment: Drugs: Inavolisib
Inavolisib will be administered orally as per schedule specified in the respective arms.

Treatment: Drugs: Bevacizumab
Bevacizumab IV will be administered as per schedule specified in the respective arm.

Treatment: Drugs: Cetuximab
Cetuximab IV will be administered as per schedule specified in the respective arm.

Treatment: Drugs: Atezolizumab
Atezolizumab IV infusion will be administered as per schedule specified in the respective arm.

Treatment: Drugs: Tiragolumab
Tiragolumab IV infusion will be administered as per schedule specified in the respective arm.

Treatment: Drugs: SY-5609
SY-5609 will be administered by mouth as per schedule specified in the respective arm.

Treatment: Drugs: Divarasib
Divarasib will be administered orally as per schedule specified in the respective arms.

Treatment: Drugs: FOLFOX
FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) IV will be administered as per schedule specified in the respective arm.

Treatment: Drugs: FOLFIRI
FOLFIRI (leucovorin, 5-fluorouracil, irinotecan) IV will be administered as per schedule specified in the respective arm.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate
Timepoint [1] 0 0
Approximately 60 months
Secondary outcome [1] 0 0
Duration of Response
Timepoint [1] 0 0
Approximately 60 months
Secondary outcome [2] 0 0
Disease Control Rate
Timepoint [2] 0 0
Approximately 60 months
Secondary outcome [3] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [3] 0 0
Approximately 60 months
Secondary outcome [4] 0 0
Plasma Concentrations of Divarasib
Timepoint [4] 0 0
At pre-defined intervals from first administration of study drug up to approximately 60 months

Eligibility
Key inclusion criteria
Inclusion Criteria

* Signed cohort-specific Informed Consent Form
* Age >= 18 years at time of signing Informed Consent Form
* Biomarker eligibility as determined at a College of American Pathologists/clinical laboratory improvement amendments (CAP/CLIA)-certified or equivalently accredited diagnostic laboratory using a validated test
* Eastern Cooperative Oncology Group (ECOG) Performance Status of <= 1
* Life expectancy >= 3 months, as determined by the investigator
* Histologically confirmed adenocarcinoma originating from the colon or rectum
* Metastatic disease
* Prior therapies for metastatic disease
* Ability to comply with the study protocol, in the investigators judgment
* Measurable disease (at least one target lesion) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
* Baseline tumor tissue samples will be collected from all patients for exploratory biomarker research
* Adequate hematologic and organ function within 14 days prior to initiation of study treatment
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures
* For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Current participation or enrollment in another interventional clinical trial. Patients who are participating in the follow-up period of an interventional clinical trial are eligible for the study.
* Any systemic anti-cancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to start of study treatment
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Pregnant or breastfeeding, or intending to become pregnant during the study
* History of or concurrent serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study or confounds the ability to interpret data from the study
* 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
* Incomplete recovery from any surgery prior to the start of study treatment that would interfere with the determination of safety or efficacy of study treatment
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
* Uncontrolled tumor-related pain
* Uncontrolled or symptomatic hypercalcemia
* Clinically significant and active liver disease
* Negative HIV test at screening, with the following exception: Patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count greater than or equal to 200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months.
* Symptomatic, untreated, or actively progressing CNS metastases
* History of leptomeningeal disease or carcinomatous meningitis
* History of malignancy other than CRC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
* Any other disease, unresolved toxicity from prior therapy, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
* Requirement for treatment with any medicinal product that contraindicates the use of any of the study treatments, may interfere with the planned treatment, affects patient compliance, or puts the patient at higher risk for treatment-related complications

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/10/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/04/2026
Actual
Sample size
Target
422
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Denmark
State/province [18] 0 0
København Ø
Country [19] 0 0
Germany
State/province [19] 0 0
Berlin
Country [20] 0 0
Germany
State/province [20] 0 0
Bochum
Country [21] 0 0
Germany
State/province [21] 0 0
Dresden
Country [22] 0 0
Germany
State/province [22] 0 0
Düsseldorf
Country [23] 0 0
Germany
State/province [23] 0 0
Hamburg
Country [24] 0 0
Germany
State/province [24] 0 0
Heilbronn
Country [25] 0 0
Germany
State/province [25] 0 0
München
Country [26] 0 0
Germany
State/province [26] 0 0
Ulm
Country [27] 0 0
Italy
State/province [27] 0 0
Campania
Country [28] 0 0
Italy
State/province [28] 0 0
Lazio
Country [29] 0 0
Italy
State/province [29] 0 0
Lombardia
Country [30] 0 0
Italy
State/province [30] 0 0
Veneto
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Goyang-si
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Jeollanam-do
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Seongnam-si
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Seoul
Country [35] 0 0
Poland
State/province [35] 0 0
Kraków
Country [36] 0 0
Poland
State/province [36] 0 0
Poznan
Country [37] 0 0
Poland
State/province [37] 0 0
Warszawa
Country [38] 0 0
Spain
State/province [38] 0 0
Barcelona
Country [39] 0 0
Spain
State/province [39] 0 0
Madrid
Country [40] 0 0
Spain
State/province [40] 0 0
Valencia
Country [41] 0 0
Taiwan
State/province [41] 0 0
Tainan
Country [42] 0 0
Taiwan
State/province [42] 0 0
Taipei City
Country [43] 0 0
Taiwan
State/province [43] 0 0
Zhongzheng Dist.
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Cambridge
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Cardiff
Country [46] 0 0
United Kingdom
State/province [46] 0 0
London
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Manchester
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: WO42758 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
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).


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04929223