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Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT04145193
Other study ID # D910CC00002
Secondary ID
Status Withdrawn
Phase Phase 2
First received
Last updated
Start date October 1, 2020
Est. completion date March 19, 2024

Study information

Verified date September 2020
Source MedImmune LLC
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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


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.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date March 19, 2024
Est. primary completion date March 19, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 101 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

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).
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)
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)
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)

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
MedImmune LLC

Outcome

Type Measure Description Time frame Safety issue
Primary ctDNA clearance ctDNA clearance is defined as the change from ctDNA positive status at baseline to ctDNA negative post baseline (6 months) From the time of first dose to 6 months post treatment
Secondary Incidence of adverse events The secondary endpoint of safety as assessed by the number of subjects with adverse events and serious adverse events From time of first dose to 90 days post last dose
Secondary Disease free survival From randomization until time of first documented incidence of disease recurrence, secondary cancer, or death due to any cause, whichever occurs first From time of first dose till end of study (5 years)
Secondary Disease free survival at 12 months Percentage of subject who are disease free at 12 months post first dose of treatment From time of first dose till end of study (5 years)
Secondary overall survival From randomization until death due to any cause From time of first dose till end of study (5 years)
Secondary Serum conenctration levels of novel agents in combination with mFOLFOX6 Pharmacokinetics of novel agents in combination with FOLFOX From Day 1 up to 90 days post last dose
Secondary Number of subjects with detectable anti-drug antibody (ADA) to novel agents in combination with mFOLFOX6 Immunogenicity of novel agents in combination with mFOLFOX6 From Day 1 up to 90 days post last dose