Description:
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).
Title
- Brief Title: COLUMBIA-1: Novel Oncology Therapies in Combination With Chemotherapy and Bevacizumab as First- Line Therapy in MSS-CRC
- 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)
Clinical Trial IDs
- ORG STUDY ID:
D910CC00001
- NCT ID:
NCT04068610
Conditions
- Metastatic Microsatellite-stable Colorectal Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| Standard of Care | FOLFOX (Oxaliplatin, Folinic acid (leucovorin), Fluorouracil (5-FU)), Bevacizumab (Avastin) | Control Arm (FOLFOX + Bevacuzimab) |
| Experimental | Durvalumab (MEDI-4736), Oleclumab (MEDI-9447) | Exp. Arm (FOLFOX + Bevacuzimab + Durvalumab + Oleclumab) |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Control Arm (FOLFOX + Bevacuzimab) | Active Comparator | 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) | |
| Exp. Arm (FOLFOX + Bevacuzimab + Durvalumab + Oleclumab) | 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 | |
Eligibility 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.
| Maximum Eligible Age: | 101 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Part 1 of the study: Number of participants with Dose Limiting Toxicities (DLTs) as a measure of safety. |
| Time Frame: | From the time of first dose through 28 days during the Part 1 of the study. |
| Safety Issue: | |
| Description: | The primary endpoint is safety as assessed by the presence of adverse events and serious adverse events |
Secondary Outcome Measures
| Measure: | Incidence of Adverse Events as a measure of safety during the treatment period |
| Time Frame: | From time of informed consent through treatment period (24 months) or up to 3 months post last dose of study treatment |
| Safety Issue: | |
| Description: | The secondary endpoint of safety as assessed by the presence of adverse events and serious adverse events |
| Measure: | Incidence of clinically significant vital sign values as a measure of safety during the treatment period |
| Time Frame: | From time of informed consent through treatment period (12 months) or up to 3 months post last dose of study treatment |
| Safety Issue: | |
| Description: | Assess the presence of clinically significant vital sign values from baseline |
| Measure: | Incidence of clinically significant laboratory values as a measure of safety during the treatment period |
| Time Frame: | From time of informed consent through treatment period (12 months) or up to 3 months post last dose of study treatment |
| Safety Issue: | |
| Description: | The secondary endpoint of safety as assessed by the presence of clinically significant laboratory values |
| Measure: | Duration of Response (DoR) as a measure of efficacy of FOLFOX plus bevacizumab plus novel oncology therapy combinations versus FOLFOX plus bevacizumab |
| Time Frame: | From time of first documented response until disease progression or up to a maximum of 5 years after randomization |
| Safety Issue: | |
| Description: | The duration from the first documentation of a subsequently confirmed OR to the first documentation of a disease progression according to RECIST v1.1 or death due to any cause, whichever occurs first. Only subjects who have achieved OR (confirmed CR or confirmed PR) will be evaluated for DoR |
| Measure: | Disease Control Rate (DCR) as a measure of efficacy of FOLFOX plus bevacizumab plus novel oncology therapy combinations versus FOLFOX plus bevacizumab |
| Time Frame: | From time of randomization until disease progression or up to a maximum of 5 years |
| Safety Issue: | |
| Description: | confirmed CR, confirmed PR, or SD based on RECIST v1.1 |
| Measure: | Progression-Free Survival (PFS) as a measure of efficacy of FOLFOX plus bevacizumab plus novel oncology therapy combinations versus FOLFOX plus bevacizumab |
| Time Frame: | From time of randomization until disease progression or up to a maximum of 5 years |
| Safety Issue: | |
| Description: | From randomization until the first documentation of disease progression according to RECIST v1.1 or death due to any cause, whichever occurs first |
| Measure: | Progression-Free Survival 12 month landmark rate (PFS-12) as a measure of efficacy of FOLFOX plus bevacizumab plus novel oncology therapy combinations versus FOLFOX plus bevacizumab |
| Time Frame: | From time of randomization until disease progression or up to a maximum of 12 months |
| Safety Issue: | |
| Description: | From randomization until the first documentation of disease progression according to RECIST v1.1 or death due to any cause, whichever occurs first |
| Measure: | Overall Survival (OS) as a measure of efficacy of FOLFOX plus bevacizumab plus novel oncology therapy combinations versus FOLFOX plus bevacizumab |
| Time Frame: | From time of randomization until death |
| Safety Issue: | |
| Description: | From randomization until death due to any cause. |
| Measure: | Serum concentration levels of novel agents in combination with FOLFOX + bevacuzimab |
| Time Frame: | From Day 1 up to 90 days post last dose |
| Safety Issue: | |
| Description: | Pharmacokinetics of novel agents in combination with FOLFOX + bevacuzimab |
| Measure: | Number of subjects with detectable anti-drug antibody (ADA) to novel agents in combination with FOLFOX + bevacuzimab |
| Time Frame: | From Day 1 up to 90 days post last dose |
| Safety Issue: | |
| Description: | Immunogenicity of novel agents in combination with FOLFOX + bevacuzimab |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | MedImmune LLC |
Trial Keywords
- Microsatellite
- colorectal
- MSS-CRC
- colon cancer
Last Updated
August 19, 2021
