Clinical Trials /

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

NCT04068610

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).

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
Standard of CareFOLFOX (Oxaliplatin, Folinic acid (leucovorin), Fluorouracil (5-FU)), Bevacizumab (Avastin)Control Arm (FOLFOX + Bevacuzimab)
ExperimentalDurvalumab (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

NameTypeDescriptionInterventions
Control Arm (FOLFOX + Bevacuzimab)Active ComparatorParts 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)
  • Standard of Care
Exp. Arm (FOLFOX + Bevacuzimab + Durvalumab + Oleclumab)ExperimentalParts 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
  • Experimental

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:Recruiting
Lead Sponsor:MedImmune LLC

Trial Keywords

  • Microsatellite
  • colorectal
  • MSS-CRC
  • colon cancer

Last Updated