A Phase I Trial Evaluating mFOLFOX6 and Avastin With Nexavar as First-Line Treatment for Metastatic Colorectal Cancer

NCT00779311 | Terminated Phase 1 Results

• 1 other identifier: AFMSMCRC0706
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is being performed at approximately 3 sites associated with Accelerated Community Oncology Research Network, Inc. (ACORN). Approximately 45 subjects will take part in this study. In this study, everyone will receive the same dose of mFOLFOX6 and Avastin. There will be five groups of subjects. Each group of subjects will receive a higher dose of Nexavar than the previous group. This will continue until a subject group has a major side effects from the dose they are given. This is so that the sponsor can determine the highest dose of Nexavar that can be used with mFOLFOX6 and AVastin (this is called the maximum tolerated dose or MTD).

Conditions

Metastatic Colorectal Cancer

Keywords

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Determination of the Maximum Tolerated Dose (MTD) of Sorafenib When Given in Combination With mFOLFOX6 and Bevacizumab

  The MTD of sorafenib was determined using a standard 3 + 3 dose escalation cohort design. The total sample and the number of patients who receive each dose depends on the frequency of dose limiting toxicities (DLT) at each dosage. If 0 out of 3 patients experience a DLT at a given dosage level, 3 patients will be enrolled at the next dosage level. If greater than or equal to 2 patients experience a DLT at a given dosage level, dosage escalation will be stopped. If 1 out of 3 patients experience a DLT at a given dosage level, 3 patients are enrolled at the same dosage level.

  MTD was assessed during the first 2 cycles of treatment (i.e., the first 4 weeks of treatment since cycle length is 2 weeks)

Secondary Outcomes (2)

• Determination of Progression Free Survival (PFS) Among Patients on This Regimen

  PFS was measured from day 1 of treatment until time of progression (assessed every 8 weeks) or death, whichever came first.

• Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen

  The PCM questionnaire was administered on day 1 of each cycle (approximately every 2 weeks) during study treatment.

Study Arms (1)

Experimenal

EXPERIMENTAL

All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle. Sorafenib will be administered daily throughout treatment beginning on day 1

Drug: sorafenib; Drug: bevacizumab; Drug: mFOLFOX6 regimen

Interventions

sorafenib DRUG

Sorafenib will be administered daily starting day 1 at 200mg QOD at Dose Level 1; 200mg/day at Dose Level 2; 200mg BID (5 days on/ 2 days off) at Dose Level 3; 200mg BID at Dose Level 4; and 400mg BID at Dose Level 5.

Also known as: Nexavar

Experimenal

bevacizumab DRUG

Bevacizumab will be administered as 5mg/kg IV on Day 1 of each treatment cycle.

Also known as: Avastin

Experimenal

mFOLFOX6 regimen DRUG

The mFOLFOX6 regimen will be administered on Day 1 of each treatment cycle. This regimen consists of oxaliplatin 85 mg/m2 IV given over 2 hours, leucovorin 400 mg/m2 IV given over 2 hours, and fluorouracil 400 mg/m2 IV bolus, followed by fluorouracil 1200 mg/m2 per day for 2 days continuous infusion.

Experimenal

Eligibility Criteria

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

You may qualify if:

• No prior chemotherapy for metastatic disease.
• Histologically proven colorectal carcinoma.
• Measurable disease by RECIST criteria.
• Age: at least 18 years.
• ECOG performance status of 0 or 1 at study entry.
• Adequate bone marrow, liver and renal function at study entry as assessed by the following:
• Hemoglobin \>9.0 g/dL.
• ANC ≥1500/mm3.
• Platelet count ≥100,000/mm3.
• Total bilirubin ≤1.5 times x ULN.
• ALT and AST ≤2.5 × ULN (≤5 × ULN for patients with liver involvement).
• Creatinine ≤1.5 × ULN.
• INR \<1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate after discussion with ACORN. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
• Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to the start of treatment.
• Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Patients should use adequate birth control for at least 3 months after the last administration of sorafenib.

You may not qualify if:

• Prior use of bevacizumab.
• Neuropathy ≥ Grade 2 per CTCAE v3.0.
• Diarrhea ≥ Grade 2 per CTCAE v3.0 within 4 weeks of study treatment start.
• ECOG performance status ≥ 2.
• Proteinuria at baseline: patients discovered to have \> 2+ proteinuria at baseline should undergo a 24 hour urine collection and must demonstrate \< 1 gram of protein in 24 hours to be eligible.
• Active malignancy other than mCRC (except non-melanoma skin cancer; in situ carcinoma of the cervix; in situ carcinoma of the breast) within the last 5 years.
• Treatment with radiotherapy within 2 weeks of enrollment.
• Cardiac disease: Congestive heart failure \> Class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
• Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/ MRI of the brain to exclude brain metastasis.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Uncontrolled hypertension defined as systolic blood pressure \> 150 mm Hg or diastolic pressure \> 90 mm Hg, despite optimal medical management.
• Known human immunodeficiency virus infection or chronic Hepatitis B or C.
• Active clinically serious infection \> Grade 2 per CTCAE v3.0.
• Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
• Pulmonary hemorrhage/bleeding event ≥ Grade 2 per CTCAE v3.0 within 4 weeks of study treatment start.

Sponsors & Collaborators

• Accelerated Community Oncology Research Network: lead
• Bayer: collaborator

Study Sites (3)

Central Georgia Cancer Care

Macon, Georgia, 31201, United States

Location

Hematology Oncology Centers of the Northern Rockies

Billings, Montana, 59101, United States

Location

The West Clinic

Memphis, Tennessee, 38120, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Sorafenib; Bevacizumab

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)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Early termination due to the MTD determined to be Dose Level 1, leading to a small number of subjects analyzed.

Results Point of Contact

• Title: Vice President of Scientific Affairs
• Organization: Accelerated Community Oncology Research Network, Inc.

mwalker@acorncro.com

901-435-5570

Study Officials

• Fred Schnell, MD

  Central Georgia Cancer Care

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2008
• First Posted: October 24, 2008
• Study Start: October 1, 2008
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: November 2, 2011
• Results First Posted: October 26, 2011

Record last verified: 2011-10

Locations

US (3)