Clinical trial NCT04145193: 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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Microsatellite-stable Colorectal Cancer
Keywords: Microsatellite stable
Colon Cancer
colorectal cancer
MSS-CRC
adjuvant
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2019-10-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 101
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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

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.

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.

Primary outcomes:
measure: ctDNA clearance
timeFrame: From the time of first dose to 6 months post treatment
Secondary outcomes:
measure: Incidence of adverse events
timeFrame: From time of first dose to 90 days post last dose
measure: Disease free survival
timeFrame: From time of first dose till end of study (5 years)
measure: Disease free survival at 12 months
timeFrame: From time of first dose till end of study (5 years)
measure: overall survival
timeFrame: From time of first dose till end of study (5 years)
measure: Serum conenctration levels of novel agents in combination with mFOLFOX6
timeFrame: From Day 1 up to 90 days post last dose
measure: Number of subjects with detectable anti-drug antibody (ADA) to novel agents in combination with mFOLFOX6
timeFrame: From Day 1 up to 90 days post last dose
Other outcomes:
Locations:
Study officials:
References: