Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Novel Oncology Therapies in Combination With Adjuvant Chemo in High-risk 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: NCT04145193
Recruitment Status : Withdrawn (Study withdrawn prior to enrollment due to changing standard of care landscape.)
First Posted : October 30, 2019
Last Update Posted : September 21, 2020
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Brief Summary:
Columbia 2 is a Phase 2 platform study to evaluate the safety and efficacy of standard of care (FOLFOX) alone and in combination with novel oncology therapies in adjuvant high-risk microsatellite-stable colorectal cancer

Condition or disease Intervention/treatment Phase
Microsatellite-stable Colorectal Cancer Drug: Standard of Care - mFOLFOX6 Drug: E1 - mFOLFOX and durvalumab Drug: E2 - mFOLFOX6, durvalumab and oleclumab Drug: E3 - mFOLFOX6, durvalumab and monalizumab Phase 2

Detailed Description:
Columbia 2 is a Phase 2, open-label, randomized, multicenter, platform study of novel oncology therapies in combination with adjuvant chemotherapy in patients with high-risk microsatellite-stable colorectal cancer.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: The study is designed to evaluate the efficacy and safety of standard-of-care adjuvant mFOLFOX6 chemotherapy alone or in combination with novel oncology therapies. The study will be conducted in subjects who have undergone radical surgical resection for Stage II or III MSS-CRC, are eligible for mFOLFOX6 adjuvant therapy, and are confirmed as ctDNA positive post-surgery.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-label, Randomized, Multicenter, Platform Study of Novel Oncology Therapies in Combination With Adjuvant Chemotherapy in High-risk, Microsatellite-stable Colorectal Cancer (COLUMBIA-2)
Estimated Study Start Date : October 1, 2020
Estimated Primary Completion Date : March 19, 2024
Estimated Study Completion Date : March 19, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Active Comparator: Control Arm (mFOLFOX6)
Parts of mFOLFOX6 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) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).
Drug: Standard of Care - mFOLFOX6
Parts of mFOLFOX6 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) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).
Other Name: FOLFOX (Oxaliplatin, Folinic acid (leucovorin), Fluorouracil (5-FU))

Drug: E1 - mFOLFOX and durvalumab

Parts of mFOLFOX6 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) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).

Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle)

Other Name: Durvalumab (MEDI-4736)

Drug: E2 - mFOLFOX6, durvalumab and oleclumab

Parts of mFOLFOX6 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) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).

Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle) Oleclumab 3,000 mg IV Q2W x5 then Q4W (Day 1 of every 14-day cycle through cycle 4 then Day 1 of every other 14-day cycle)

Other Name: Durvalumab (MEDI-4736) + Oleclumab (MEDI-9447)

Drug: E3 - mFOLFOX6, durvalumab and monalizumab

Parts of mFOLFOX6 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) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).

Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle) Monalizumab 750 mg IV, Q2W (Day 1 of every 14-day cycle)

Other Name: Durvalumab (MEDI-4736) + Monalizumab (IPH2201)

Experimental: Durvalumab
Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle)
Drug: E1 - mFOLFOX and durvalumab

Parts of mFOLFOX6 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) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).

Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle)

Other Name: Durvalumab (MEDI-4736)

Drug: E2 - mFOLFOX6, durvalumab and oleclumab

Parts of mFOLFOX6 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) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).

Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle) Oleclumab 3,000 mg IV Q2W x5 then Q4W (Day 1 of every 14-day cycle through cycle 4 then Day 1 of every other 14-day cycle)

Other Name: Durvalumab (MEDI-4736) + Oleclumab (MEDI-9447)

Drug: E3 - mFOLFOX6, durvalumab and monalizumab

Parts of mFOLFOX6 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) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).

Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle) Monalizumab 750 mg IV, Q2W (Day 1 of every 14-day cycle)

Other Name: Durvalumab (MEDI-4736) + Monalizumab (IPH2201)

Experimental: Oleclumab
Oleclumab 3,000 mg IV Q2W x5 then Q4W (Day 1 of every 14-day cycle through cycle 4 then Day 1 of every other 14-day cycle)
Drug: E2 - mFOLFOX6, durvalumab and oleclumab

Parts of mFOLFOX6 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) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).

Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle) Oleclumab 3,000 mg IV Q2W x5 then Q4W (Day 1 of every 14-day cycle through cycle 4 then Day 1 of every other 14-day cycle)

Other Name: Durvalumab (MEDI-4736) + Oleclumab (MEDI-9447)

Experimental: Monalizumab
Monalizumab 750 mg IV, Q2W (Day 1 of every 14-day cycle)
Drug: E3 - mFOLFOX6, durvalumab and monalizumab

Parts of mFOLFOX6 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) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).

Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle) Monalizumab 750 mg IV, Q2W (Day 1 of every 14-day cycle)

Other Name: Durvalumab (MEDI-4736) + Monalizumab (IPH2201)




Primary Outcome Measures :
  1. ctDNA clearance [ Time Frame: From the time of first dose to 6 months post treatment ]
    ctDNA clearance is defined as the change from ctDNA positive status at baseline to ctDNA negative post baseline (6 months)


Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: From time of first dose to 90 days post last dose ]
    The secondary endpoint of safety as assessed by the number of subjects with adverse events and serious adverse events

  2. Disease free survival [ Time Frame: From time of first dose till end of study (5 years) ]
    From randomization until time of first documented incidence of disease recurrence, secondary cancer, or death due to any cause, whichever occurs first

  3. Disease free survival at 12 months [ Time Frame: From time of first dose till end of study (5 years) ]
    Percentage of subject who are disease free at 12 months post first dose of treatment

  4. overall survival [ Time Frame: From time of first dose till end of study (5 years) ]
    From randomization until death due to any cause

  5. Serum conenctration levels of novel agents in combination with mFOLFOX6 [ Time Frame: From Day 1 up to 90 days post last dose ]
    Pharmacokinetics of novel agents in combination with FOLFOX

  6. Number of subjects with detectable anti-drug antibody (ADA) to novel agents in combination with mFOLFOX6 [ Time Frame: From Day 1 up to 90 days post last dose ]
    Immunogenicity of novel agents in combination with mFOLFOX6



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 101 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Histologically proven Stage II or Stage III CRC

    Subjects must also meet the following criteria:

    1. Eligible for 6 months of mFOLFOX6 adjuvant chemotherapy within 8 weeks after surgery
    2. Must NOT have received prior systemic chemotherapy, immunotherapy, or radiotherapy for treatment of CRC.
    3. Must NOT have defective DNA mismatch repair (MSI) as documented by testing
  5. Margin-negative (R0; defined as >1 mm clearance) surgical resection
  6. Postoperative ctDNA-positive status defined by the presence of ctDNA derived from plasma; determined using a validated assay per protocol
  7. Subjects must have adequate organ function
  8. Body weight > 35 kg
  9. Adequate method of contraception per protocol

Exclusion Criteria:

  1. Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
  2. Evidence of metastatic disease (including presence of tumor cells in ascites or peritoneal carcinomatosis resected "en bloc").
  3. History of allogeneic organ transplantation.
  4. Active or prior documented autoimmune disorders within the past 5 years as noted in the protocol.
  5. Cardiac and vascular criteria:

    1. History of venous thrombosis within the past 3 months prior to the scheduled first dose of study treatment.
    2. 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 prior to the scheduled first dose of study treatment.
    3. New York Heart Association (NYHA) Class II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or uncontrolled hypertension.
    4. History of hypertensive crisis/hypertensive encephalopathy within the past 6 months prior to the scheduled first dose of study treatment.
    5. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms
  6. Uncontrolled intercurrent illness, see the protocol for details.
  7. History of another primary malignancy except for: (a) Malignancy treated with curative intent and with no known active disease ≥ 5 years prior to the scheduled first dose of study treatment and of low potential risk for recurrence
  8. History of active primary immunodeficiency.
  9. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.
  10. Known allergy or hypersensitivity to any of the investigational product or noninvestigational product formulations.
  11. Any condition that, in the opinion of the investigator, would prevent the initiation of 6 months adjuvant therapy within 8 weeks of surgery
  12. Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment.
  13. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the scheduled first dose of study treatment, or anticipation of the need for major surgical procedure during the course of the study.
  14. Current or prior use of immunosuppressive medication within 14 days prior to the scheduled first dose of study treatment.
Layout table for additonal information
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT04145193    
Other Study ID Numbers: D910CC00002
First Posted: October 30, 2019    Key Record Dates
Last Update Posted: September 21, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
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
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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MedImmune LLC:
Microsatellite stable
Colon Cancer
colorectal cancer
MSS-CRC
adjuvant
Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Leucovorin
Fluorouracil
Oxaliplatin
Durvalumab
Antibodies, Monoclonal
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances