Clinical trial NCT04068610: COLUMBIA-1: Novel Oncology Therapies in Combination With Chemotherapy and Bevacizumab as First- Line Therapy in MSS-CRC
Official 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Metastatic Microsatellite-stable Colorectal Cancer
Keywords: Microsatellite
colorectal
MSS-CRC
colon cancer
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2019-08-28
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 101
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is designed to concurrently evaluate potential novel combinations with clinical promise using a 2-part approach.

Part 1 is a Phase 1b study of safety, and Part 2 is a Phase 2 study of efficacy and safety. The treatment regimens evaluated in Part 2 will depend on the evaluation of safety outcomes in Part 1.

Following a screening period of up to 28 days, participants will be centrally assigned (Part 1) or randomized (Part 2) to one of the open study arms. In both study parts, study treatment may be administered until disease progression or any discontinuation criteria are met.

In Part 2, experimental arms may be closed early based on futility from results of a planned interim analysis for each study arm. In both parts, new experimental arms consisting of FOLFOX and bevacizumab plus novel agent(s) may be added based on emerging nonclinical and clinical data via protocol amendment.
Primary purpose: TREATMENT

Brief summary: COLUMBIA-1 is a Phase 1b/2 platform study to evaluate the safety and efficacy of standard of care (FOLFOX plus bevacizumab) alone and in combination with novel oncology therapies in first-line metastatic microsatellite-stable colorectal cancer (MSS-CRC).

Detailed description: COLUMBIA-1 is a Phase 1b/2, open-label, multicenter, randomized, multidrug platform study to evaluate the safety and efficacy of standard of care (FOLFOX plus bevacizumab) in combination with novel oncology therapies in patients with first-line metastatic MSS-CRC. The study is designed to concurrently evaluate potential novel combinations with clinical promise using a 2-part approach. Part 1 is a Phase 1b study of safety, and Part 2 is a Phase 2 study of efficacy and safety.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part 1
timeFrame: Day 1 through 90 days after the last dose of study drug (approximately 2.8 years)
measure: Number of Participants With Dose Limiting Toxicities (DLTs) in Part 1
timeFrame: From Day 1 to 28 days after the first dose of novel oncology therapy (durvalumab and oleclumab)
measure: Number of Participants With at Least 2-Grade Shift From Baseline to Worst Toxicity Grade in Clinical Laboratory Parameters in Part 1
timeFrame: Baseline (Day 1) through 90 days after the last dose of study drug (approximately 2.8 years)
measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part 1
timeFrame: Day 1 through 90 days after the last dose of study drug (approximately 2.8 years)
measure: Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in Part 2
timeFrame: Randomization through end of study (approximately 2.6 years)
Secondary outcomes:
measure: Percentage of Participants With OR Per RECIST v1.1 in Part 1
timeFrame: First dose (Day 1) through end of study (approximately 2.8 years)
measure: Best Overall Response (BOR) Per RECIST v1.1 in Part 1
timeFrame: First dose (Day 1) through end of study (approximately 2.8 years)
measure: Duration of Response (DoR) Per RECIST v1.1 in Part 1
timeFrame: First dose (Day 1) through end of study (approximately 2.8 years)
measure: Percentage of Participants With Disease Control (DC) Per RECIST v1.1 in Part 1
timeFrame: First dose (Day 1) through end of study (approximately 2.8 years)
measure: Progression-Free Survival (PFS) Per RECIST v1.1 in Part 1
timeFrame: Assignment through end of study (approximately 2.8 years)
measure: Percentage of Participants With PFS at 12 Months (PFS-12) Per RECIST v1.1 in Part 1
timeFrame: Assignment through 12 months
measure: Overall Survival (OS) Per RECIST v1.1 in Part 1
timeFrame: First dose (Day 1) through end of study (approximately 2.8 years)
measure: Number of Participants With TEAEs and TESAEs in Part 2
timeFrame: Day 1 through 90 days after the last dose of study drug (approximately 2.6 years)
measure: Number of Participants With at Least 2-Grade Shift From Baseline to Worst Toxicity Grade in Clinical Laboratory Parameters in Part 2
timeFrame: Baseline (Day 1) through 90 days after the last dose of study drug (approximately 2.6 years)
measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part 2
timeFrame: Day 1 through 90 days after the last dose of study drug (approximately 2.6 years)
measure: BOR Per RECIST v1.1 in Part 2
timeFrame: Randomization through end of study (approximately 2.6 years)
measure: DoR Per RECIST v1.1 in Part 2
timeFrame: Randomization through end of study (approximately 2.6 years)
measure: Percentage of Participants With DC Per RECIST v1.1 in Part 2
timeFrame: Randomization through end of study (approximately 2.6 years)
measure: PFS Per RECIST v1.1 in Part 2
timeFrame: Randomization through end of study (approximately 2.6 years)
measure: Percentage of Participants With PFS at 12 Months (PFS-12) Per RECIST v1.1 in Part 2
timeFrame: Randomization through 12 months
measure: OS Per RECIST v1.1 in Part 2
timeFrame: Randomization through end of study (approximately 2.6 years)
measure: Serum Concentrations of Durvalumab in Part 1 (S1) and Part 2 (E1)
timeFrame: 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
measure: Serum Concentrations of Oleclumab in Part 1 (S1) and Part 2 (E1)
timeFrame: 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
measure: Serum Concentrations of Bevacizumab in Part 1 (S1)
timeFrame: Pre-dose on Day 1 of Cycle 1, 2, 7, 13, and 27
measure: Number of Participants With Positive Anti-Drug Antibodies (ADA) to Durvalumab in Part 1 (S1) and Part 2 (E1)
timeFrame: 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)
measure: Number of Participants With Positive ADA to Oleclumab in Part 1 (S1) and Part 2 (E1)
timeFrame: 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)
measure: Number of Participants With Positive ADA to Bevacizumab in Part 1 (S1)
timeFrame: Pre-dose on D1 of C1 (BL), 2, 7, 13, 27, and 90 days post last dose of study drug (approximately 2.8 years)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Sacramento
country: United States
facility: Research Site
state: California
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: New York
country: United States
facility: Research Site
state: New York
city: Canton
country: United States
facility: Research Site
state: Ohio
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Charlottesville
country: United States
facility: Research Site
state: Virginia
city: Clayton
country: Australia
facility: Research Site
city: Heidelberg
country: Australia
facility: Research Site
city: Melbourne
country: Australia
facility: Research Site
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Nantes
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
Study officials:
References: