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

NCT04145193 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: D910CC00002
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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

Conditions

Microsatellite-stable Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Incidence of adverse events

  From time of first dose to 90 days post last dose

• Disease free survival

  From time of first dose till end of study (5 years)

• Disease free survival at 12 months

  From time of first dose till end of study (5 years)

• overall survival

  From time of first dose till end of study (5 years)

• Serum conenctration levels of novel agents in combination with mFOLFOX6

  From Day 1 up to 90 days post last dose

Study Arms (4)

Control Arm (mFOLFOX6)

ACTIVE COMPARATOR

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).

Drug: Standard of Care - mFOLFOX6; Drug: E1 - mFOLFOX and durvalumab; Drug: E2 - mFOLFOX6, durvalumab and oleclumab; Drug: E3 - mFOLFOX6, durvalumab and monalizumab

Durvalumab

EXPERIMENTAL

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

Drug: E1 - mFOLFOX and durvalumab; Drug: E2 - mFOLFOX6, durvalumab and oleclumab; Drug: E3 - mFOLFOX6, durvalumab and monalizumab

Oleclumab

EXPERIMENTAL

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)

Drug: E2 - mFOLFOX6, durvalumab and oleclumab

Monalizumab

EXPERIMENTAL

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

Drug: E3 - mFOLFOX6, durvalumab and monalizumab

Interventions

Standard of Care - mFOLFOX6 DRUG

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).

Also known as: FOLFOX (Oxaliplatin, Folinic acid (leucovorin), Fluorouracil (5-FU))

Control Arm (mFOLFOX6)

E1 - mFOLFOX and durvalumab DRUG

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)

Also known as: Durvalumab (MEDI-4736)

Control Arm (mFOLFOX6); Durvalumab

E2 - mFOLFOX6, durvalumab and oleclumab DRUG

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)

Also known as: Durvalumab (MEDI-4736) + Oleclumab (MEDI-9447)

Control Arm (mFOLFOX6); Durvalumab; Oleclumab

E3 - mFOLFOX6, durvalumab and monalizumab DRUG

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)

Also known as: Durvalumab (MEDI-4736) + Monalizumab (IPH2201)

Control Arm (mFOLFOX6); Durvalumab; Monalizumab

Eligibility Criteria

• Age: 18 Years - 101 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and any locally required authorization obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Age ≥ 18 years at the time of screening
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Histologically proven Stage II or Stage III CRC
• Subjects must also meet the following criteria:
• Eligible for 6 months of mFOLFOX6 adjuvant chemotherapy within 8 weeks after surgery
• Must NOT have received prior systemic chemotherapy, immunotherapy, or radiotherapy for treatment of CRC.
• Must NOT have defective DNA mismatch repair (MSI) as documented by testing
• Margin-negative (R0; defined as \>1 mm clearance) surgical resection
• Postoperative ctDNA-positive status defined by the presence of ctDNA derived from plasma; determined using a validated assay per protocol
• Subjects must have adequate organ function
• Body weight \> 35 kg
• Adequate method of contraception per protocol

You may not qualify if:

• 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.
• Evidence of metastatic disease (including presence of tumor cells in ascites or peritoneal carcinomatosis resected "en bloc").
• History of allogeneic organ transplantation.
• Active or prior documented autoimmune disorders within the past 5 years as noted in the protocol.
• Cardiac and vascular criteria:
• History of venous thrombosis within the past 3 months prior to the scheduled first dose of study treatment.
• 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.
• New York Heart Association (NYHA) Class II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or uncontrolled hypertension.
• History of hypertensive crisis/hypertensive encephalopathy within the past 6 months prior to the scheduled first dose of study treatment.
• Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms
• Uncontrolled intercurrent illness, see the protocol for details.
• 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
• History of active primary immunodeficiency.
• Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.
• Known allergy or hypersensitivity to any of the investigational product or noninvestigational product formulations.

Sponsors & Collaborators

• MedImmune LLC: lead

MeSH Terms

Conditions

Colonic Neoplasms; Colorectal Neoplasms

Interventions

Folfox protocol; Oxaliplatin; Leucovorin; Fluorouracil; durvalumab; monalizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 16, 2019
• First Posted: October 30, 2019
• Study Start: October 1, 2020
• Primary Completion: March 19, 2024
• Study Completion: March 19, 2024
• Last Updated: September 21, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 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.
• Access Criteria: 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.