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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05330429




Registration number
NCT05330429
Ethics application status
Date submitted
8/04/2022
Date registered
15/04/2022

Titles & IDs
Public title
Study of Magrolimab Given Together With FOLFIRI/BEV in Patients With Previously Treated Advanced Inoperable Metastatic Colorectal Cancer (mCRC)
Scientific title
A Phase 2, Randomized, Open-Label Study Evaluating the Safety and Efficacy of Magrolimab in Combination With Bevacizumab and FOLFIRI Versus Bevacizumab and FOLFIRI in Previously Treated Advanced Inoperable Metastatic Colorectal Cancer (mCRC)
Secondary ID [1] 0 0
2022-500177-13
Secondary ID [2] 0 0
GS-US-587-6156
Universal Trial Number (UTN)
Trial acronym
ELEVATE CRC
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 - Magrolimab
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Irinotecan
Treatment: Drugs - Fluorouracil
Treatment: Drugs - Leucovorin

Experimental: Safety Run-in Cohort: Magrolimab + Bevacizumab + FOLFIRI - Participants will receive magrolimab in de-escalating doses to establish recommended Phase 2 dose (RP2D) in combination with + bevacizumab (5 mg/kg every 2 weeks) + FOLFIRI (irinotecan 180 mg/m\^2 + leucovorin 400 mg/m\^2 + fluorouracil 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous on Days 1, 2, 15, and 16 of a 28-Day Cycle).

Experimental: Randomized Cohort: Magrolimab + Bevacizumab + FOLFIRI - Participants will receive the RP2D determined in the Safety Run-in cohort of magrolimab in combination with bevacizumab (5 mg/kg every 2 weeks) + FOLFIRI (irinotecan 180 mg/m\^2 + leucovorin 400 mg/m\^2 + fluorouracil 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous on Days 1, 2, 15, and 16 of a 28-Day Cycle).

Active comparator: Randomized Cohort: Bevacizumab + FOLFIRI - Participants will receive bevacizumab (5 mg/kg every 2 weeks) + FOLFIRI (irinotecan 180 mg/m\^2 + leucovorin 400 mg/m\^2 + fluorouracil 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous on Days 1, 2, 15, and 16 of a 28-Day Cycle).


Treatment: Drugs: Magrolimab
Administered intravenously

Treatment: Drugs: Bevacizumab
Administered intravenously

Treatment: Drugs: Irinotecan
Administered intravenously

Treatment: Drugs: Fluorouracil
Administered intravenously

Treatment: Drugs: Leucovorin
Administered intravenously
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety Run-in Cohort: Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Timepoint [1] 0 0
First dose date up to 28 days
Primary outcome [2] 0 0
Safety Run-in Cohort: Percentage of Participants Experiencing Adverse Events (AEs) According to the NCI-CTCAE Version 5.0
Timepoint [2] 0 0
First dose date up to 3 years
Primary outcome [3] 0 0
Safety Run-in Cohort: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI-CTCAE Version 5.0
Timepoint [3] 0 0
First dose date up to 3 years
Primary outcome [4] 0 0
Randomized Cohort: Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [1] 0 0
Randomized Cohort: Objective Response Rate (ORR) as Determined by Investigator Assessment Using RECIST Version 1.1
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
Randomized Cohort: Duration of Response (DOR) as Assessed by Investigator Assessment Per RECIST Version 1.1
Timepoint [2] 0 0
Up to 3 years
Secondary outcome [3] 0 0
Randomized Cohort: Overall Survival (OS)
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [4] 0 0
Randomized Cohort: Change From Baseline of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire EORTC-QLQ-C30 Score
Timepoint [4] 0 0
Baseline, up to 3 years
Secondary outcome [5] 0 0
Randomized Cohort: Change From Baseline of the 5-level EuroQol 5 dimensions questionnaire (EQ-5D-5L) Score
Timepoint [5] 0 0
Baseline, up to 3 years
Secondary outcome [6] 0 0
Randomized Cohort: the Change From Baseline of the Functional Assessment of Cancer Therapy (FACT) Colorectal Symptom Index (FCSI) Score
Timepoint [6] 0 0
Baseline, up to 3 years
Secondary outcome [7] 0 0
Safety Run-in and Randomized Cohorts: Magrolimab Concentration Versus Time
Timepoint [7] 0 0
Up to end of treatment (approximately 3 years)
Secondary outcome [8] 0 0
Safety Run-in and Randomized Cohorts: Antidrug Antibodies (ADA) to Magrolimab
Timepoint [8] 0 0
Up to end of treatment (approximately 3 years)

Eligibility
Key inclusion criteria
Key

* Previously treated individuals with inoperable metastatic colorectal cancer (mCRC) who are ineligible for checkpoint inhibitor therapy (microsatellite instability (MSI)-H or mismatch repair deficient (dMMR) and are excluded).
* Histologically or cytologically confirmed adenocarcinoma originating in the colon or rectum (excluding appendiceal and anal canal cancers) who have progressed on or after 1 prior systemic therapy in the setting where curative resection is not indicated. This therapy must have included chemotherapy based on 5-FU or capecitabine with oxaliplatin and either bevacizumab, or for patients with RAS wild-type and left-sided tumors, bevacizumab, cetuximab, or panitumumab.
* Measurable disease (RECIST V1.1 criteria).
* Individuals must have an eastern cooperative oncology group (ECOG) performance status of 0 or 1.
* Life expectancy of at least 12 weeks.
* Laboratory measurements, blood counts: adequate hemoglobin, neutrophil, and platelet counts
* Adequate liver function.
* Adequate renal function.

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior anticancer therapy including chemotherapy, hormonal therapy, or investigational agents within 3 weeks or within at least 4 half-lives prior to magrolimab dosing (up to a maximum of 4 weeks), whichever is shorter.
* Known v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E or MSI-H mutations or dMMR.
* Persistent Grade 2 or more gastrointestinal bleeding.
* Individuals with prior irinotecan therapy.
* Clinically significant coronary artery disease or myocardial infarction within 6 months prior to inclusion.
* Peripheral neuropathy of more than Grade 2 (CTCAE Version 5.0).
* Known dihydropyrimidine dehydrogenase deficiency.
* Acute intestinal obstruction or subobstruction, history of inflammatory intestinal disease or extended resection of the small intestine. Presence of a colonic prosthesis.
* Unhealed wound, active gastric or duodenal ulcer, or bone fracture.
* History of abdominal fistulas, trachea-oesophageal fistulas, any other Grade 4 gastrointestinal perforations, nongastrointestinal fistulas, or intra-abdominal abscesses 6 months prior to screening.
* Uncontrolled arterial hypertension.
* Thromboembolic event in the 6 months before inclusion (eg, transitory ischemic stroke, stroke, subarachnoid hemorrhage) except peripheral deep vein thrombosis treated with anticoagulants.
* Active central nervous system (CNS) disease. Individuals with asymptomatic and stable, treated CNS lesions (radiation and/or surgery and/or other CNS-directed therapy who have not received corticosteroids for at least 4 weeks) are allowed.
* Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of packed RBC transfusions during the 4-week period prior to screening.
* History of hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the last 3 months.
* Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient.
* Known inherited or acquired bleeding disorders.
* Significant disease or medical conditions, as assessed by the investigator and sponsor, that would substantially increase the risk-benefit ratio of participating in the study.
* Second malignancy, except treated basal cell or localized squamous skin carcinomas, or localized prostate cancer.
* Uncontrolled pleural effusion.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/06/2024
Sample size
Target
Accrual to date
Final
77
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Westmead Hospital - Blacktown
Recruitment hospital [2] 0 0
Kinghorn Cancer Centre - Darlinghurst
Recruitment hospital [3] 0 0
Southside Cancer Care Centre - Miranda
Recruitment hospital [4] 0 0
Genesis Care North Shore - St Leonards
Recruitment hospital [5] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [6] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [7] 0 0
Austin Health - Heidelberg
Recruitment hospital [8] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2228 - Miranda
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment postcode(s) [5] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [6] 0 0
5042 - Bedford Park
Recruitment postcode(s) [7] 0 0
3084 - Heidelberg
Recruitment postcode(s) [8] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
South Dakota
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Belgium
State/province [13] 0 0
Haine-Saint-Paul
Country [14] 0 0
Belgium
State/province [14] 0 0
Libramont-Chevigny
Country [15] 0 0
Canada
State/province [15] 0 0
Ottawa
Country [16] 0 0
Canada
State/province [16] 0 0
Toronto
Country [17] 0 0
France
State/province [17] 0 0
Besançon
Country [18] 0 0
France
State/province [18] 0 0
Lyon
Country [19] 0 0
France
State/province [19] 0 0
Paris
Country [20] 0 0
France
State/province [20] 0 0
Tours
Country [21] 0 0
Germany
State/province [21] 0 0
Dresden
Country [22] 0 0
Germany
State/province [22] 0 0
Munchen
Country [23] 0 0
Hong Kong
State/province [23] 0 0
Hong Kong
Country [24] 0 0
Italy
State/province [24] 0 0
Meldola
Country [25] 0 0
Italy
State/province [25] 0 0
Padova
Country [26] 0 0
Italy
State/province [26] 0 0
Pisa
Country [27] 0 0
Italy
State/province [27] 0 0
San Giovanni Rotondo
Country [28] 0 0
Italy
State/province [28] 0 0
Vicenza
Country [29] 0 0
Puerto Rico
State/province [29] 0 0
San Juan
Country [30] 0 0
Spain
State/province [30] 0 0
Barcelona
Country [31] 0 0
Spain
State/province [31] 0 0
L'Hospitalet de Llobregat
Country [32] 0 0
Spain
State/province [32] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
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


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/NCT05330429