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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04145193
Ethics application status
Date submitted
16/10/2019
Date registered
30/10/2019

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
Timepoint [1] 0 0
From the time of first dose to 6 months post treatment
Secondary outcome [1] 0 0
Incidence of 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
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
Timepoint [3] 0 0
From time of first dose till end of study (5 years)
Secondary outcome [4] 0 0
overall survival
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
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
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
Sex
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
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/10/2020
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
19/03/2024
Actual
Sample size
Target
Accrual to date
Final
0
Recruitment in Australia
Recruitment state(s)

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04145193