Clinical Trials /

Novel Oncology Therapies in Combination With Adjuvant Chemo in High-risk MSS-CRC

NCT04145193

Description:

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

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Novel Oncology Therapies in Combination With Adjuvant Chemo in High-risk MSS-CRC
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: D910CC00002
  • NCT ID: NCT04145193

Conditions

  • Microsatellite-stable Colorectal Cancer

Interventions

DrugSynonymsArms
Standard of Care - mFOLFOX6FOLFOX (Oxaliplatin, Folinic acid (leucovorin), Fluorouracil (5-FU))Control Arm (mFOLFOX6)
E1 - mFOLFOX and durvalumabDurvalumab (MEDI-4736)Control Arm (mFOLFOX6)
E2 - mFOLFOX6, durvalumab and oleclumabDurvalumab (MEDI-4736) + Oleclumab (MEDI-9447)Control Arm (mFOLFOX6)
E3 - mFOLFOX6, durvalumab and monalizumabDurvalumab (MEDI-4736) + Monalizumab (IPH2201)Control Arm (mFOLFOX6)

Purpose

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

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.
    

Trial Arms

NameTypeDescriptionInterventions
Control Arm (mFOLFOX6)Active ComparatorParts 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).
  • Standard of Care - mFOLFOX6
  • E1 - mFOLFOX and durvalumab
  • E2 - mFOLFOX6, durvalumab and oleclumab
  • E3 - mFOLFOX6, durvalumab and monalizumab
DurvalumabExperimentalDurvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle)
  • E1 - mFOLFOX and durvalumab
  • E2 - mFOLFOX6, durvalumab and oleclumab
  • E3 - mFOLFOX6, durvalumab and monalizumab
OleclumabExperimentalOleclumab 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)
  • E2 - mFOLFOX6, durvalumab and oleclumab
MonalizumabExperimentalMonalizumab 750 mg IV, Q2W (Day 1 of every 14-day cycle)
  • E3 - mFOLFOX6, durvalumab and monalizumab

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. 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.
      
Maximum Eligible Age:101 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:ctDNA clearance
Time Frame:From the time of first dose to 6 months post treatment
Safety Issue:
Description:ctDNA clearance is defined as the change from ctDNA positive status at baseline to ctDNA negative post baseline (6 months)

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:From time of first dose to 90 days post last dose
Safety Issue:
Description:The secondary endpoint of safety as assessed by the number of subjects with adverse events and serious adverse events
Measure:Disease free survival
Time Frame:From time of first dose till end of study (5 years)
Safety Issue:
Description:From randomization until time of first documented incidence of disease recurrence, secondary cancer, or death due to any cause, whichever occurs first
Measure:Disease free survival at 12 months
Time Frame:From time of first dose till end of study (5 years)
Safety Issue:
Description:Percentage of subject who are disease free at 12 months post first dose of treatment
Measure:overall survival
Time Frame:From time of first dose till end of study (5 years)
Safety Issue:
Description:From randomization until death due to any cause
Measure:Serum conenctration levels of novel agents in combination with mFOLFOX6
Time Frame:From Day 1 up to 90 days post last dose
Safety Issue:
Description:Pharmacokinetics of novel agents in combination with FOLFOX
Measure: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
Safety Issue:
Description:Immunogenicity of novel agents in combination with mFOLFOX6

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:MedImmune LLC

Trial Keywords

  • Microsatellite stable
  • Colon Cancer
  • colorectal cancer
  • MSS-CRC
  • adjuvant

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