Phase II Study of Zaltrap and Chemotherapy for Advanced Resectable Colorectal Cancer

NCT02046538 | Withdrawn Phase 2 DMC

• 2 other identifiers: 13090143022012-AFL-18
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to establish the safety of Zaltrap in patients who undergo pre-operative chemotherapy with Zaltrap. The investigators hypothesize that Zaltrap my impact colorectal cancer growth and metastasis.

Conditions

Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum

Outcome Measures

Primary Outcomes (2)

• Number of adverse events experienced

  Capture the number of adverse events experienced by advanced resectable colorectal cancer subjects treated with pre-operative chemotherapy and Zaltrap

  Approximately 24 months per patient

• Number of subjects who demonstrate a response to pre-operative chemotherapy and zaltrap

  Capture the number of subjects who demonstrate an improvement (response) in colorectal cancer status after being treated with pre-operative chemotherapy and zaltrap.

  Approximately 24 months per patient

Secondary Outcomes (1)

• Survival duration without disease progression

  2 years per patient

Study Arms (2)

Postoperative Chemo WITH Zaltrap

EXPERIMENTAL

Subjects will receive 3 months of chemotherapy consisting of either FOLFOX (oxaliplatin, leucovorin, 5-FU) or FOLFIRI (Irinotecan, leucovorin, 5-FU) in the case of liver limited CRC, or FOLFOX (in the case of rectal cancer). Zaltrap will be administered with chemotherapy every 2 weeks for the first 5 out of 6 planned treatment cycles. After a standard 3-4 week recovery period (i.e. 5-6 weeks from the last Zaltrap dose), patients will undergo standard resection. At the time of resection, the tumor will be collected for biomarker discovery. Following resection, patients will receive chemotherapy with zaltrap for 3 additional months. Patients may continue zaltrap (without chemotherapy) until disease recurrence or up to an additional 15 months.

Drug: Leucovorin; Drug: Oxaliplatin; Drug: 5-FU; Drug: Irinotecan

Postoperative chemo WITHOUT zaltrap

ACTIVE COMPARATOR

Subjects will receive 3 months of chemotherapy consisting of either FOLFOX (oxaliplatin, leucovorin, 5-FU) or FOLFIRI (Irinotecan, leucovorin, 5-FU) in the case of liver limited CRC, or FOLFOX (in the case of rectal cancer). Zaltrap will be administered with chemotherapy every 2 weeks for the first 5 out of 6 planned treatment cycles. After a standard 3-4 week recovery period (i.e. 5-6 weeks from the last Zaltrap dose), patients will undergo standard resection. At the time of resection, the tumor will be collected for biomarker discovery. Following resection, patients will receive chemotherapy (without zaltrap) for 3 additional months.

Drug: Leucovorin; Drug: Oxaliplatin; Drug: 5-FU; Drug: Irinotecan

Interventions

Leucovorin DRUG

400 mg/m2 IV over two hours (or administered concurrently with oxaliplatin or irinotecan, depending on the assigned regimen)

Also known as: Wellcovorin

Postoperative Chemo WITH Zaltrap; Postoperative chemo WITHOUT zaltrap

Oxaliplatin DRUG

85 mg/m2 IV over two hours

Also known as: Eloxatin

Postoperative Chemo WITH Zaltrap; Postoperative chemo WITHOUT zaltrap

5-FU DRUG

400 mg/m2 IV bolus, then 2400 mg/m2 continuous IV infusion over 46-48 hours

Also known as: Adrucil, fluorouracil

Postoperative Chemo WITH Zaltrap; Postoperative chemo WITHOUT zaltrap

Irinotecan DRUG

180 mg/m2 IV over 90 minutes

Also known as: Camptosar

Postoperative Chemo WITH Zaltrap; Postoperative chemo WITHOUT zaltrap

Eligibility Criteria

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

You may qualify if:

• Patients must have pathologically confirmed adenocarcinoma of the colon or rectum.
• In patients with liver-limited metastatic colorectal cancer, a curative approach is indicated following evaluation by hepatobiliary surgeon as part of multidisciplinary management. Select patients requiring two stage procedure are also eligible following evaluation by hepatobiliary surgeon as part of multidisciplinary management.
• In patients with rectal cancer, primary tumor that is clinically T3-4 or N + (evaluation by colorectal surgery is required as part of multidisciplinary approach).
• No prior chemotherapy for metastatic disease is allowed for patients with CRC-liver mets. (adjuvant FOLFOX is permitted)
• No prior chemotherapy for proximal rectal cancer is allowed
• ECOG Performance status ≤ 2.
• Age \>18 years old.
• Patients must have adequate bone marrow, kidney, and liver function as assessed by laboratory parameters.
• WBC ≥ 3,000/uL
• Total Bilirubin ≤ 1.5 x upper limits of normal
• AST (SGOT) ≤ 3 x upper limits of normal
• ALT (SGPT) ≤ 3 x upper limits of normal
• Hemoglobin ≥ 9.0 g/dl (without transfusion within 7 d)
• ANC ≥ 1500 /ml
• Platelets ≥100 K/ml (without transfusion)

You may not qualify if:

• Patients with untreated CNS metastases.
• Significant medical co-morbidity that would preclude safe administration of cytotoxic therapy, including but not limited to:
• Cardiovascular disease
• Unstable angina
• Myocardial infarction/ CABG \< 3 months prior to study initiation
• Untreated coronary artery disease
• NYHA class III or IV heart failure
• Ongoing serious infection
• Bacteremia or sepsis requiring intravenous antibiotics
• HIV with AIDS defining illness
• Inadequate oral nutritional intake: Requirement for daily intravenous fluids or total parenteral nutrition.
• Neurological: Stroke ≤ 6 months
• Psychiatric illness/social situations that would limit compliance with study requirement
• Patients may not receive another investigational agent.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Ziv-aflibercept.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Sanofi: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

Leucovorin; Oxaliplatin; Fluorouracil; Irinotecan

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; 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)

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

Study Officials

• Manish A. Shah, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 23, 2014
• First Posted: January 27, 2014
• Study Start: February 1, 2014
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2018
• Last Updated: January 25, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)