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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04145193




Registration number
NCT04145193
Ethics application status
Date submitted
16/10/2019
Date registered
30/10/2019
Date last updated
15/05/2020

Titles & IDs
Public title
Novel Oncology Therapies in Combination With Adjuvant Chemo in High-risk MSS-CRC
Scientific 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)
Secondary ID [1] 0 0
D910CC00002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Microsatellite-stable Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Standard of Care - mFOLFOX6
Treatment: Drugs - E1 - mFOLFOX and durvalumab
Treatment: Drugs - E2 - mFOLFOX6, durvalumab and oleclumab
Treatment: Drugs - E3 - mFOLFOX6, durvalumab and monalizumab

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).

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

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)

Experimental: Monalizumab - Monalizumab 750 mg IV, Q2W (Day 1 of every 14-day cycle)


Treatment: Drugs: 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).

Treatment: Drugs: 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)

Treatment: Drugs: 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)

Treatment: Drugs: 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)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
ctDNA clearance - ctDNA clearance is defined as the change from ctDNA positive status at baseline to ctDNA negative post baseline (6 months)
Timepoint [1] 0 0
From the time of first dose to 6 months post treatment
Secondary outcome [1] 0 0
Incidence of adverse events - The secondary endpoint of safety as assessed by the number of subjects with adverse events and serious adverse events
Timepoint [1] 0 0
From time of first dose to 90 days post last dose
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
From time of first dose till end of study (5 years)
Secondary outcome [3] 0 0
Disease free survival at 12 months - Percentage of subject who are disease free at 12 months post first dose of treatment
Timepoint [3] 0 0
From time of first dose till end of study (5 years)
Secondary outcome [4] 0 0
overall survival - From randomization until death due to any cause
Timepoint [4] 0 0
From time of first dose till end of study (5 years)
Secondary outcome [5] 0 0
Serum conenctration levels of novel agents in combination with mFOLFOX6 - Pharmacokinetics of novel agents in combination with FOLFOX
Timepoint [5] 0 0
From Day 1 up to 90 days post last dose
Secondary outcome [6] 0 0
Number of subjects with detectable anti-drug antibody (ADA) to novel agents in combination with mFOLFOX6 - Immunogenicity of novel agents in combination with mFOLFOX6
Timepoint [6] 0 0
From Day 1 up to 90 days post last dose

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
101 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Clayton
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
Montana
Country [13] 0 0
United States of America
State/province [13] 0 0
Nevada
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Oregon
Country [18] 0 0
United States of America
State/province [18] 0 0
Rhode Island
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Virginia
Country [22] 0 0
United States of America
State/province [22] 0 0
Washington
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
Canada
State/province [24] 0 0
Quebec
Country [25] 0 0
France
State/province [25] 0 0
Brest
Country [26] 0 0
France
State/province [26] 0 0
Lille
Country [27] 0 0
France
State/province [27] 0 0
Montpellier
Country [28] 0 0
France
State/province [28] 0 0
Nantes
Country [29] 0 0
France
State/province [29] 0 0
Paris
Country [30] 0 0
France
State/province [30] 0 0
St Etienne
Country [31] 0 0
France
State/province [31] 0 0
Villejuif
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Seoul
Country [33] 0 0
Spain
State/province [33] 0 0
Barcelona
Country [34] 0 0
Spain
State/province [34] 0 0
Cordoba
Country [35] 0 0
Spain
State/province [35] 0 0
Madrid
Country [36] 0 0
Spain
State/province [36] 0 0
Orense
Country [37] 0 0
Spain
State/province [37] 0 0
Valencia
Country [38] 0 0
Taiwan
State/province [38] 0 0
Tainan City
Country [39] 0 0
Taiwan
State/province [39] 0 0
Taipei City
Country [40] 0 0
Taiwan
State/province [40] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
MedImmune LLC
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/show/NCT04145193
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
information.center@astrazeneca.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04145193