COLUMBIA-1: Novel Oncology Therapies in Combination with Chemotherapy and Bevacizumab as First- Line Therapy in MSS-CRC

Study identifier:D910CC00001

ClinicalTrials.gov identifier:NCT04068610

EudraCT identifier:N/A

CTIS identifier:N/A

Recruitment Complete

Official Title

A Phase 1b/2, 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)

Medical condition

Metastatic Microsatellite-stable Colorectal Cancer

Phase

Phase 1/2

Healthy volunteers

Study drug

Standard of Care, Experimental

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 101 Years

Date

Study Start Date: 13 Sept 2019

Estimated Primary Completion Date: 31 Oct 2023

Estimated Study Completion Date: 31 Oct 2023

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Oct 2022 by MedImmune, LLC

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Written informed consent and any locally required authorization obtained from the subject/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. Subjects 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) Subjects must NOT have defective DNA mismatch repair (MSI) as documented by testing. (c) Subjects 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. Subjects must have at least one lesion that is measurable by RECIST v1.1 (Eisenhauer et al, 2009).
6. Subjects must have adequate organ function.
7. Subjects with medical conditions requiring systemic anticoagulation (eg, atrial fibrillation) are eligible provided that both of the following criteria are met: - The subject has an in-range INR on a stable dose of oral anticoagulant or be on a stable dose of low molecular weight heparin. - The subject 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

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 NCI 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.

No locations available

Arms	Assigned Interventions
Active Comparator: Control Arm (FOLFOX + Bevacuzimab) Parts of FOLFOX are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 2400 mg/m2 administered by continuous IV infusion over 46 to 48 hours Q2W (Day 1-2 of every 14-day cycle). Note: 5-FU will be administered as infusion only. Bevacizumab 5 mg/kg IV infusion Q2W (Day 1 of every 14-day cycle)	Drug: Standard of Care Parts of FOLFOX are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 2400 mg/m2 administered by continuous IV infusion over 46 to 48 hours Q2W (Day 1-2 of every 14-day cycle). Note: 5-FU will be administered as infusion only. Bevacizumab 5 mg/kg IV infusion Q2W (Day 1 of every 14-day cycle) Other Name: FOLFOX (Oxaliplatin, Folinic acid (leucovorin), Fluorouracil (5-FU)) Other Name: Bevacizumab (Avastin)
Experimental: Exp. Arm (FOLFOX + Bevacuzimab + Durvalumab + Oleclumab) Parts of FOLFOX are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 2400 mg/m2 administered by continuous IV infusion over 46 to 48 hours Q2W (Day 1-2 of every 14-day cycle). Note: 5-FU will be administered as infusion only. Bevacizumab 5 mg/kg IV infusion Q2W (Day 1 of every 14-day cycle) Durvalumab 1500 mg IV Q4W Oleclumab 3000mg IV Q2W x 4 then Q4W	Drug: Experimental Parts of FOLFOX are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 2400 mg/m2 administered by continuous IV infusion over 46 to 48 hours Q2W (Day 1-2 of every 14-day cycle). Note: 5-FU will be administered as infusion only. Bevacizumab 5 mg/kg IV infusion Q2W (Day 1 of every 14-day cycle) Durvalumab 1500 mg IV Q4W Oleclumab 3000mg IV Q2W x 4 then Q4W Other Name: Durvalumab (MEDI-4736) Other Name: Oleclumab (MEDI-9447)

Arms

Assigned Interventions

Active Comparator: Control Arm (FOLFOX + Bevacuzimab)
Parts of FOLFOX are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 2400 mg/m2 administered by continuous IV infusion over 46 to 48 hours Q2W (Day 1-2 of every 14-day cycle). Note: 5-FU will be administered as infusion only. Bevacizumab 5 mg/kg IV infusion Q2W (Day 1 of every 14-day cycle)

Drug: Standard of Care
Parts of FOLFOX are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 2400 mg/m2 administered by continuous IV infusion over 46 to 48 hours Q2W (Day 1-2 of every 14-day cycle). Note: 5-FU will be administered as infusion only. Bevacizumab 5 mg/kg IV infusion Q2W (Day 1 of every 14-day cycle)

Other Name: FOLFOX (Oxaliplatin, Folinic acid (leucovorin), Fluorouracil (5-FU))

Other Name: Bevacizumab (Avastin)

Experimental: Exp. Arm (FOLFOX + Bevacuzimab + Durvalumab + Oleclumab)
Parts of FOLFOX are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 2400 mg/m2 administered by continuous IV infusion over 46 to 48 hours Q2W (Day 1-2 of every 14-day cycle). Note: 5-FU will be administered as infusion only. Bevacizumab 5 mg/kg IV infusion Q2W (Day 1 of every 14-day cycle) Durvalumab 1500 mg IV Q4W Oleclumab 3000mg IV Q2W x 4 then Q4W

Drug: Experimental
Parts of FOLFOX are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 2400 mg/m2 administered by continuous IV infusion over 46 to 48 hours Q2W (Day 1-2 of every 14-day cycle). Note: 5-FU will be administered as infusion only. Bevacizumab 5 mg/kg IV infusion Q2W (Day 1 of every 14-day cycle) Durvalumab 1500 mg IV Q4W Oleclumab 3000mg IV Q2W x 4 then Q4W

Other Name: Durvalumab (MEDI-4736)

Other Name: Oleclumab (MEDI-9447)

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]