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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04068610




Registration number
NCT04068610
Ethics application status
Date submitted
1/08/2019
Date registered
28/08/2019

Titles & IDs
Public title
COLUMBIA-1: Novel Oncology Therapies in Combination With Chemotherapy and Bevacizumab as First- Line Therapy in MSS-CRC
Scientific title
A Phase Ib/II, Open-label, Multicenter Study of Novel Oncology Therapies in Combination With Chemotherapy and Bevacizumab as First-line Therapy in Metastatic Microsatellite-stable Colorectal Cancer (COLUMBIA-1)
Secondary ID [1] 0 0
2019-000974-44
Secondary ID [2] 0 0
D910CC00001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Microsatellite-stable 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 - Durvalumab
Treatment: Drugs - Oleclumab
Treatment: Drugs - FOLFOX
Treatment: Drugs - Bevacizumab

Experimental: Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab - Participants in Part 1 safety run-in arm (S1) will receive intravenous (IV) infusions of FOLFOX (5-fluorouracil \[5-FU\]: 2400 mg/m\^2 over 46-48 hours \[Day 1 and 2 of every 14-day Cycle\], oxaliplatin: 85 mg/m\^2, folinic acid: 400 mg/m\^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg every 4 weeks (Q4W) and IV oleclumab 3000 mg every 2 weeks (Q2W) till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion will be met.

Experimental: Part 2 (C1): FOLFOX + Bevacizumab - Participants in Part 2 control 1 arm (C1) will receive IV infusions of FOLFOX (5-FU: 2400 mg/m\^2 over 46-48 hours \[Day 1 and 2 of every 14-day Cycle\], oxaliplatin: 85 mg/m\^2, folinic acid: 400 mg/m\^2) in combination with IV bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion will be met.

Experimental: Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab - Participants in Part 2 experimental 1 arm (E1) will receive IV infusions of FOLFOX (5-FU: 2400 mg/m\^2 over 46-48 hours \[Day 1 and 2 of every 14-day Cycle\], oxaliplatin: 85 mg/m\^2, folinic acid: 400 mg/m\^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion will be met.


Treatment: Drugs: Durvalumab
Participants will receive IV infusion of durvalumab as stated in arm description.

Treatment: Drugs: Oleclumab
Participants will receive IV infusion of oleclumab as stated in arm description.

Treatment: Drugs: FOLFOX
Participants will receive IV infusion of FOLFOX (5-FU, oxaliplatin, and folinic acid) as stated in arm description.

Treatment: Drugs: Bevacizumab
Participants will receive IV infusion of bevacizumab as stated in arm description.

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

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part 1
Timepoint [1] 0 0
Day 1 through 90 days after the last dose of study drug (approximately 2.8 years)
Primary outcome [2] 0 0
Number of Participants With Dose Limiting Toxicities (DLTs) in Part 1
Timepoint [2] 0 0
From Day 1 to 28 days after the first dose of novel oncology therapy (durvalumab and oleclumab)
Primary outcome [3] 0 0
Number of Participants With at Least 2-Grade Shift From Baseline to Worst Toxicity Grade in Clinical Laboratory Parameters in Part 1
Timepoint [3] 0 0
Baseline (Day 1) through 90 days after the last dose of study drug (approximately 2.8 years)
Primary outcome [4] 0 0
Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part 1
Timepoint [4] 0 0
Day 1 through 90 days after the last dose of study drug (approximately 2.8 years)
Primary outcome [5] 0 0
Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in Part 2
Timepoint [5] 0 0
Randomization through end of study (approximately 2.6 years)
Secondary outcome [1] 0 0
Percentage of Participants With OR Per RECIST v1.1 in Part 1
Timepoint [1] 0 0
First dose (Day 1) through end of study (approximately 2.8 years)
Secondary outcome [2] 0 0
Best Overall Response (BOR) Per RECIST v1.1 in Part 1
Timepoint [2] 0 0
First dose (Day 1) through end of study (approximately 2.8 years)
Secondary outcome [3] 0 0
Duration of Response (DoR) Per RECIST v1.1 in Part 1
Timepoint [3] 0 0
First dose (Day 1) through end of study (approximately 2.8 years)
Secondary outcome [4] 0 0
Percentage of Participants With Disease Control (DC) Per RECIST v1.1 in Part 1
Timepoint [4] 0 0
First dose (Day 1) through end of study (approximately 2.8 years)
Secondary outcome [5] 0 0
Progression-Free Survival (PFS) Per RECIST v1.1 in Part 1
Timepoint [5] 0 0
Assignment through end of study (approximately 2.8 years)
Secondary outcome [6] 0 0
Percentage of Participants With PFS at 12 Months (PFS-12) Per RECIST v1.1 in Part 1
Timepoint [6] 0 0
Assignment through 12 months
Secondary outcome [7] 0 0
Overall Survival (OS) Per RECIST v1.1 in Part 1
Timepoint [7] 0 0
First dose (Day 1) through end of study (approximately 2.8 years)
Secondary outcome [8] 0 0
Number of Participants With TEAEs and TESAEs in Part 2
Timepoint [8] 0 0
Day 1 through 90 days after the last dose of study drug (approximately 2.6 years)
Secondary outcome [9] 0 0
Number of Participants With at Least 2-Grade Shift From Baseline to Worst Toxicity Grade in Clinical Laboratory Parameters in Part 2
Timepoint [9] 0 0
Baseline (Day 1) through 90 days after the last dose of study drug (approximately 2.6 years)
Secondary outcome [10] 0 0
Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part 2
Timepoint [10] 0 0
Day 1 through 90 days after the last dose of study drug (approximately 2.6 years)
Secondary outcome [11] 0 0
BOR Per RECIST v1.1 in Part 2
Timepoint [11] 0 0
Randomization through end of study (approximately 2.6 years)
Secondary outcome [12] 0 0
DoR Per RECIST v1.1 in Part 2
Timepoint [12] 0 0
Randomization through end of study (approximately 2.6 years)
Secondary outcome [13] 0 0
Percentage of Participants With DC Per RECIST v1.1 in Part 2
Timepoint [13] 0 0
Randomization through end of study (approximately 2.6 years)
Secondary outcome [14] 0 0
PFS Per RECIST v1.1 in Part 2
Timepoint [14] 0 0
Randomization through end of study (approximately 2.6 years)
Secondary outcome [15] 0 0
Percentage of Participants With PFS at 12 Months (PFS-12) Per RECIST v1.1 in Part 2
Timepoint [15] 0 0
Randomization through 12 months
Secondary outcome [16] 0 0
OS Per RECIST v1.1 in Part 2
Timepoint [16] 0 0
Randomization through end of study (approximately 2.6 years)
Secondary outcome [17] 0 0
Serum Concentrations of Durvalumab in Part 1 (S1) and Part 2 (E1)
Timepoint [17] 0 0
Part 1: Pre-dose on Day 1 of Cycle 1, 3, 7, 13; Part 2 (E1): Pre-dose on Day 1 of Cycle 1, 3, 7, 13, and 27
Secondary outcome [18] 0 0
Serum Concentrations of Oleclumab in Part 1 (S1) and Part 2 (E1)
Timepoint [18] 0 0
Part 1: Pre-dose on Day 1 of Cycle 1, 2, 7, and 13; Part 2 (E1): Pre-dose on Day 1 of Cycle 1, 2, 7, 13, and 27
Secondary outcome [19] 0 0
Serum Concentrations of Bevacizumab in Part 1 (S1)
Timepoint [19] 0 0
Pre-dose on Day 1 of Cycle 1, 2, 7, 13, and 27
Secondary outcome [20] 0 0
Number of Participants With Positive Anti-Drug Antibodies (ADA) to Durvalumab in Part 1 (S1) and Part 2 (E1)
Timepoint [20] 0 0
Part 1: Pre-dose on Day(D)1 of Cycles(C)1 (baseline [BL]), 3, 7, 13, and 90 days post last dose of study drug (approximately 2.8 years); Part 2(E1):Pre-dose on D1 of C1 (BL), 3, 7, 13, 27, and 90 days post last dose of study drug (approximately 2.6 years)
Secondary outcome [21] 0 0
Number of Participants With Positive ADA to Oleclumab in Part 1 (S1) and Part 2 (E1)
Timepoint [21] 0 0
Part 1: Pre-dose on D1 of C1 (BL), 2, 7, 13, and 90 days post last dose of study drug (approximately 2.8 years); Part 2 (E1): Pre-dose on D1 of C1 (BL), 2, 7, 13, 27, and 90 days post last dose of study drug (approximately 2.6 years)
Secondary outcome [22] 0 0
Number of Participants With Positive ADA to Bevacizumab in Part 1 (S1)
Timepoint [22] 0 0
Pre-dose on D1 of C1 (BL), 2, 7, 13, 27, and 90 days post last dose of study drug (approximately 2.8 years)

Eligibility
Key inclusion criteria
1. Written informed consent and any locally required authorization obtained from the participant/legal representative prior to performing any protocol-related procedures, including screening evaluations.
2. Age = 18 years at the time of screening.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Participants must have histologic documentation of advanced or metastatic CRC and: (a) A documented mutation test during screening and confirmed tumor locations from disease assessment for enrollment. (b) Participants must NOT have defective deoxyribonucleic acid (DNA) mismatch repair (MSI) as documented by testing. (c) Participants must not have received any prior systemic therapy for recurrent/metastatic disease (prior adjuvant chemotherapy or radio-chemotherapy is acceptable so long as progression was not within 6 months of completing the adjuvant regimen).
5. Participants must have at least one lesion that is measurable by RECIST v1.1 (Eisenhauer et al, 2009).
6. Participants must have adequate organ function.
7. Participants with medical conditions requiring systemic anticoagulation (eg, atrial fibrillation) are eligible provided that both of the following criteria are met: - The participant has an in-range International Normalized Ratio (INR) on a stable dose of oral anticoagulant or be on a stable dose of low molecular weight heparin. - The participant has no active bleeding or pathological condition that carries a high risk of bleeding.
8. Body weight >35 kg.
9. Adequate method of contraception per protocol.
Minimum age
18 Years
Maximum age
101 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of allogeneic organ transplantation.
2. Active or prior documented autoimmune disorders within the past 5 years.
3. History of venous thrombosis within the past 3 months.
4. Cardiovascular criteria: (a) Presence of acute coronary syndrome including myocardial infarction or unstable angina pectoris, other arterial thrombotic event including cerebrovascular accident or transient ischemic attack or stroke within the past 6 months. (b) New York Heart Association (NYHA) class II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or uncontrolled hypertension. (c) History of hypertensive crisis/hypertensive encephalopathy within the past 6 months.
5. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) = 470 ms.
6. No significant history of bleeding events or gastrointestinal perforation.
7. Uncontrolled intercurrent illness.
8. History of another primary malignancy except for: (a) Malignancy treated with curative intent and with no known active disease = 5 years of low potential risk for recurrence. (b) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. (c) Adequately treated carcinoma in situ without evidence of disease.
9. History of active primary immunodeficiency.
10. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.
11. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
12. Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade > 1 from previous anticancer therapy.
13. History of leptomeningeal disease or cord compression.
14. Untreated central nervous system (CNS) metastases.
15. Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
16. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
17. Prior immunotherapy or anti-angiogenics.
18. Receipt of live attenuated vaccine within the past 30 days.
19. Major surgical procedure, open biopsy, or significant traumatic injury within the past 28 days.
20. Current or prior use of immunosuppressive medication within the past 14 days, with exceptions per protocol.

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 1
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Clayton
Recruitment hospital [2] 0 0
Research Site - Heidelberg
Recruitment hospital [3] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
3000 - 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
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Nevada
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Rhode Island
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
France
State/province [11] 0 0
Nantes
Country [12] 0 0
France
State/province [12] 0 0
Villejuif
Country [13] 0 0
Spain
State/province [13] 0 0
Barcelona
Country [14] 0 0
Spain
State/province [14] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
MedImmune LLC
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Address 0 0
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)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available to whom?
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.