Aflibercept and FOLFOX6 Treatment for Previously Untreated Stage IV Colorectal Cancer

NCT01652196 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: OSU 11182NCI-2012-01167
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 6

Brief Summary

This phase II trial studies how well giving aflibercept together with combination chemotherapy works in treating patients with previously untreated colon or rectal cancer that is metastatic or locally advanced and cannot be removed by surgery. Aflibercept may stop the growth of colon or rectal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving aflibercept together with combination chemotherapy may kill more tumor cells

Conditions

Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

Keywords

colorectal cancer; rectal cancer; FOLFOX; Aflibercept

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Alive and Progression-free at 15 Months

  Assuming that the number of treatment successes (alive and progression-free) is binomially distributed, proportion estimates along with their corresponding exact 95% confidence intervals will be calculated.

  At 15 months from initiation of therapy

Secondary Outcomes (7)

• Objective Response Rate (ORR) Defined as the Proportion of Patients Who Achieve a PR or CR Based on RECIST 1.1 Criteria Divided by the Total Number of Evaluable Patients

  Up to 4 weeks post-treatment

• Percentage of Patients Able to Undergo Surgery

  Up to 4 weeks post-treatment

• Progression Free Survival (PFS)

  From study entry to the time of progressive disease and/or death, assessed up to 4 weeks post-treatment, assessed up to 4 years and 2 months

• Overall Survival

  From study entry to time of death due to any cause, assessed up to 4 weeks post-treatment

• Incidence of Severe (Grade 3+) Adverse Events or Toxicities, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0

  Up to 4 weeks post-treatment

Study Arms (1)

Aflibercept (combination chemotherapy)

EXPERIMENTAL

Patients receive aflibercept and fluorouracil and then continuously over 46 hours on days 1 and 15.If leucovorin is not available due to drug shortages the regimen should be administered with the leucovorin omitted. Correlative Studies are required to be available before enrolling on the study. A fresh biopsy is only required if there is insufficient material for analysis. Repeat tumor biopsies after 8 weeks of therapy are optional and will only be performed at the Ohio State University Medical Center.DCE MRI (dynamic contrast-enhanced magnetic resonance imaging)images at weeks 0, and after 8 weeks +/- 1 week of treatment(after Cycle 2). 18FDG-PET is a functional imaging technique that relies on tumor uptake of radiolabeled tracer 18 fluorodeoxyglucose (18FDG).FDG-PET is a widely-used imaging modality in the detection and monitoring of a variety of metastatic cancers,including colorectal cancer (99-102).

Biological: aflibercept; Drug: oxaliplatin; Drug: leucovorin; Drug: fluorouracil; Other: Correlative Studies; Procedure: DCE MRI; Radiation: f18FDG-PET; Procedure: PET (positron emission tomography)

Interventions

aflibercept BIOLOGICAL

4 mg/kg as a 1-hour IV(intervenous) infusion

Also known as: vascular endothelial growth factor trap, VEGF Trap, VEGF Trap R1R2

Aflibercept (combination chemotherapy)

oxaliplatin DRUG

85 mg/m2 IV infused over 2 hours

Also known as: 1-OHP, Dacotin, Dacplat, Eloxatin, L-OHP

Aflibercept (combination chemotherapy)

leucovorin DRUG

200 mg/m2 (Or levoleucovorin 100 mg/m2. If leucovorin is not available due to drug shortages the regimen should be administered with the leucovorin omitted) IV over 2 hours. Alternatively, leucovorin may be administered (via separate infusion lines) concurrently with oxaliplatin

Also known as: CF, CFR, LV

Aflibercept (combination chemotherapy)

fluorouracil DRUG

400 mg/m2 IV bolus over 5-15 minutes, then 2400 mg/m2 continuous IV infusion over 46 hours.

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU

Aflibercept (combination chemotherapy)

Correlative Studies OTHER

Patients are required to have tissue available before enrolling on the study. A fresh biopsy is only required if there is insufficient material for analysis. Repeat tumor biopsies after 8 weeks of therapy are optional and will only be performed at the Ohio State University Medical Center.

Also known as: laboratory biomarker analysis

Aflibercept (combination chemotherapy)

DCE MRI PROCEDURE

Images at weeks 0, and after 8 weeks +/- 1 week of treatment (after Cycle 2).

Also known as: Dynamic contrast-enhanced magnetic resonance imaging

Aflibercept (combination chemotherapy)

f18FDG-PET RADIATION

18FDG-PET is a functional imaging technique that relies on tumor uptake of radiolabeled tracer 18 fluorodeoxyglucose (18FDG). FDG-PET is a widely-used imaging modality in the detection and monitoring of a variety of metastatic cancers, including colorectal cancer (99-102).

Also known as: 18FDG, FDG, fludeoxyglucose, F 18

Aflibercept (combination chemotherapy)

PET (positron emission tomography) PROCEDURE

Correlative studies

Also known as: FDG-PET, PET, PET scan, tomography, emission computed

Aflibercept (combination chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed adenocarcinoma of colorectal origin that is metastatic or locally advanced and unresectable
• Measurable disease, as defined by RECIST 1.1 criteria: one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 10 mm with spiral computed tomography (CT) scan (CT scan slice thickness no greater than 5 mm) malignant lymph nodes will be considered measurable if they are \>= 15 mm in short axis
• Must not have received any prior systemic therapy for metastatic or locally advanced CRC; prior VEGF inhibitors are not allowed
• Prior adjuvant therapy for CRC including fluoropyrimidines either alone or in combination with oxaliplatin is allowed, provided that all therapy was completed \>= 12 months from cancer recurrence, therapy duration was =\< 6 months, and all prior toxicities have completely resolved (residual grade 1 neuropathy is allowed)
• Life expectancy \>= 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Hemoglobin \>= 9 g/dL (blood transfusion permitted to attain this value)
• Absolute neutrophil count \>= 1,500/uL
• Platelets \>= 100,000/uL
• Total bilirubin =\< 2 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (may be =\< 5x ULN if increase is due to metastatic disease)
• Creatinine =\< 1.5 x institutional ULN or creatinine clearance \>= 60 mL/min/1.73 m2 for patients with creatinine levels above institutional U
• Urine protein:creatinine ratio (UPCR) \< 1 or \< 500 mg protein/24 hr
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• May not be receiving any other investigational agents
• Patients who have received any prior locoregional therapy for metastatic disease (e.g. radiofrequency/microwave ablation, Yttrium-90 radioembolization, transarterial chemoembolization, or surgical resection) are excluded
• Patients with known or suspected brain metastases, carcinomatous meningitis, uncontrolled seizure disorder, active intracranial bleeding or active neurologic disorder are excluded
• Patients with an active second primary malignancy or history of malignancy within the 5 years of enrollment are excluded, with the exception of non-melanoma skin cancers and cervical cancer which has been treated with curative therapy
• Grade \>= 2 sensory neuropathy at the time of enrollment
• Major surgery within 4 weeks of study start date; the surgical incision should be fully healed prior to initiation of aflibercept
• Female or male patients of reproductive capacity unwilling to use methods appropriate to prevent pregnancy are excluded; effective contraception is required for at least 3 months following the last administration of aflibercept
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled hypertension (blood pressure \[BP\] must be well controlled \< 160/90), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, or any condition that the principal investigator (PI) feels would make the patient ineligible
• Positive pregnancy screening test with a minimum sensitivity of 25 IU/L of human chorionic gonadotropin (hCG) within 72 hours of registration; breastfeeding women are also excluded
• History of pulmonary embolus within 3 months or deep venous thrombosis (DVT) within 4 weeks of enrollment; patients on anticoagulation must be on a stable dose of warfarin with a therapeutic-range international normalized ratio (INR) or on a stable dose of low molecular weight heparin
• Active congestive heart failure (New York Heart Association \[NYHA\] class II-IV)
• History of an arterial thrombotic vascular event including cerebrovascular accident (CVA), myocardial infarction (MI), unstable angina, coronary or peripheral arterial bypass graft, or transient ischemic attack (TIA) within 6 months
• Serious or non-healing wound, ulcer or bone fracture at the time of medication administration
• History of treatment-resistant peptic ulcer disease, erosive esophagitis, gastritis, or diverticulitis within 3 months
• History of gastrointestinal (GI) perforation within 5 years; current or prior intestinal fistulas are also excluded

Sponsors & Collaborators

• John Hays: lead
• Sanofi: collaborator

Study Sites (6)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Links

• Jamesline

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Colorectal Neoplasms

Interventions

aflibercept; Oxaliplatin; Leucovorin; Fluorouracil; Fluorodeoxyglucose F18; Magnetic Resonance Spectroscopy; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole

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; Deoxyglucose; Deoxy Sugars; Carbohydrates; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Dr. John Hays
• Organization: The Ohio State University Comprehensive Cancer Center

John.hay@osumc.edu

614-293-6529

Study Officials

• John Hays, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 25, 2012
• First Posted: July 27, 2012
• Study Start: November 14, 2012
• Primary Completion: August 6, 2019
• Study Completion: August 30, 2022
• Last Updated: February 5, 2025
• Results First Posted: February 5, 2025

Record last verified: 2025-02

Locations

US (6)