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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04068610
Recruitment Status : Active, not recruiting
First Posted : August 28, 2019
Last Update Posted : April 15, 2020
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Tracking Information
First Submitted Date  ICMJE August 1, 2019
First Posted Date  ICMJE August 28, 2019
Last Update Posted Date April 15, 2020
Actual Study Start Date  ICMJE September 13, 2019
Estimated Primary Completion Date February 22, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 23, 2019)
  • 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. ]
    The primary endpoint is safety as assessed by the presence of adverse events and serious adverse events
  • Part 2 of the study: Objective Response (OR) rate as a measure of antitumor activity of FOLFOX plus bevacizumab plus novel oncology therapy combinations versus FOLFOX plus bevacizumab. [ Time Frame: From randomization/enrollment until progression, or the last evaluable disease assessment in the absence of PD prior to the initiation of subsequent anticancer therapy or discontinuation from the study, whichever occurs first, assessed up to 5 years. ]
    Best overall response of confirmed CR or confirmed PR according to RECIST v1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 23, 2019)
  • 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 ]
    The secondary endpoint of safety as assessed by the presence of adverse events and serious adverse events
  • 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 ]
    Assess the presence of clinically significant vital sign values from baseline
  • 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 ]
    The secondary endpoint of safety as assessed by the presence of clinically significant laboratory values
  • 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 ]
    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
  • 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 ]
    confirmed CR, confirmed PR, or SD based on RECIST v1.1
  • 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 ]
    From randomization until the first documentation of disease progression according to RECIST v1.1 or death due to any cause, whichever occurs first
  • 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 ]
    From randomization until the first documentation of disease progression according to RECIST v1.1 or death due to any cause, whichever occurs first
  • 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 ]
    From randomization until death due to any cause.
  • Serum concentration levels of novel agents in combination with FOLFOX + bevacuzimab [ Time Frame: From Day 1 up to 90 days post last dose ]
    Pharmacokinetics of novel agents in combination with FOLFOX + bevacuzimab
  • 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 ]
    Immunogenicity of novel agents in combination with FOLFOX + bevacuzimab
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE COLUMBIA-1: Novel Oncology Therapies in Combination With Chemotherapy and Bevacizumab as First- Line Therapy in MSS-CRC
Official Title  ICMJE 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)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
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, subjects 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.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Microsatellite-stable Colorectal Cancer
Intervention  ICMJE
  • 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 Names:
    • FOLFOX (Oxaliplatin, Folinic acid (leucovorin), Fluorouracil (5-FU))
    • Bevacizumab (Avastin)
  • 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 Names:
    • Durvalumab (MEDI-4736)
    • Oleclumab (MEDI-9447)
Study Arms  ICMJE
  • 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)
    Intervention: Drug: Standard of Care
  • 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

    Intervention: Drug: Experimental
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 23, 2019)
112
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 22, 2024
Estimated Primary Completion Date February 22, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 101 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   France,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04068610
Other Study ID Numbers  ICMJE D910CC00001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: 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 Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: 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.
Access Criteria: 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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party MedImmune LLC
Study Sponsor  ICMJE MedImmune LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account MedImmune LLC
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP