Study of Gsmms Interfereon in Metastatic Colorectal Carcinoma - Full Text View

Sponsors and Collaborators:	Accelerated Community Oncology Research Network InterMune
Information provided by:	Accelerated Community Oncology Research Network
ClinicalTrials.gov Identifier:	NCT00786643

Purpose

The first phase of the trial is designed to find a safe biologically active dose (SBD) of the GFL combination. The second phase is to evaluate the toxicities associated with adding IFN-y to 5 FU/LV.

Condition	Intervention	Phase
Colorectal Carcinoma	Drug: 5-Fluorouracil Drug: Leucovorin Calcium Drug: Gamma-Interferon-1b (IFN-γ) Drug: Bevacizumab	Phase I Phase II

MedlinePlus related topics: Calcium Cancer Colorectal Cancer

Drug Information available for: Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Folic acid Bevacizumab Fluorouracil Calcium gluconate Interferons Interferon gamma-1b Amphetamine Sodium phosphate, dibasic Amino acids, branched-chain Methamphetamine Tranilast

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Crossover Assignment, Safety/Efficacy Study
Official Title:	Phase I/II Study of Gamma Interferon (IFN-γ) Added to Bolus + Infusional 5-Fluorouracil (5-FU) and Leucovorin (LV) +/- Bevacizumab (BV) in Metastatic Colorectal Carcinoma

Further study details as provided by Accelerated Community Oncology Research Network:

Primary Outcome Measures:

To determine a safe biologically active dose of IFN-γ added to a bolus + infusional regimen of (GFL) for metastatic colorectal cancer [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
To evaluate the overall response rate of metastatic colorectal cancer to GFL+/-BV at the SBD identified in 1.1 [ Time Frame: 56 days ] [ Designated as safety issue: Yes ]
To determine a safe biologically active dose of IFN-γ added to a bolus + infusional regimen of 5-FU/LV [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To evaluate the toxicities associated with adding IFN-γ to 5- FU/LV [ Time Frame: cycle 1 ,1st week ] [ Designated as safety issue: Yes ]
To evaluate the toxicities associated with adding IFN-γ to 5-FU/LV plus BV [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
To evaluate pharmacokinetics of (a) 5-FU and (b) IFN-γ when given in the schedule specified in this protocol [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]
To evaluate the level of Fas expression in peripheral blood mononuclear cells (PBMC) at various time points after IFN-γ administration [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]
To evaluate time to progression, the progression-free survival and overall survival for patients treated with GFL (+/- BV) [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]
To evaluate the early response rate to GFL at 8 weeks [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
To evaluate the toxicity of GFL (+/- BV) [ Time Frame: week 2 ] [ Designated as safety issue: Yes ]
To evaluate pharmacokinetics of (a) 5-FU and (b) IFN-γ [ Time Frame: week 2 ] [ Designated as safety issue: Yes ]
To evaluate the level of Fas expression in PBMC after IFN-γ administration [ Time Frame: week 2 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	28
Study Start Date:	April 2003
Estimated Study Completion Date:	April 2009
Estimated Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Intervention Details:

5-FU is commercially available as an antimetabolite that interferes with RNA and DNA synthesis. Fluororacil Injection (Roche Laboratories): 50 mg/ml, 10 ml vials; clear, yellow, aqueous solution; Fluorouracil (Cetus, Lyphomed, Americal): 50 mg/ml; 10 ml, 20 ml, 100 ml ampules; Fluorouracil (Solopak): 50 mg/ml; 10 ml, 50 ml, 100 ml vials; 10 ml ampules; Adrucil (Adria Laboratories): 50 mg/ml; 10 ml ampules.

Leucovorin calcium is commercially available, and is a stable reduced formyl derivative and the active form of folic acid.Leucovorin Calcium (Folinic Acid); Leucovorin Calcium (calcium folinate; citrovorum factor; N 5—formyltetrahydrofolate; 5-formyl- FH4; folinic acid; folinic acid-SF; (6RS)-folinic acid; Wellcovorin).

ACTIMMUNE® (Gamma-Interferon-1b), a biologic response modifier, is a single-chain polypeptide containing 140 amino acids.

Bevacizumab is a clear to slightly opalescent, sterile liquid ready for parenteral administration. Each 5ml. glass vial (100-mg, 25 mg/mL) contains sodium phosphate, trehalose, polysorbate 20, and Sterile Water for Injection (SWFI), USP

Detailed Description:

Primary Objectives - Phase I

To determine a safe biologically active dose (SBD) of IFN-γ added to a bolus + infusional regimen of 5-FU/LV (GFL) for metastatic colorectal cancer
To determine a safe biologically active dose of IFN-γ added to a bolus + infusional regimen of 5-FU/LV (GFL) plus bevacizumab (BV) for metastatic colorectal cancer

Secondary Objectives - Phase I

To evaluate the toxicities associated with adding IFN-γ to 5-
To evaluate the toxicities associated with adding IFN-γ to 5-FU/LV plus BV
To evaluate pharmacokinetics of (a) 5-FU and (b) IFN-γ when given in the schedule specified in this protocol
To evaluate the level of Fas expression in peripheral blood mononuclear cells (PBMC) at various time points after IFN-γ administration

Primary Objective - Phase II

1. To evaluate the overall response rate of metastatic colorectal cancer to GFL+/-BV at the SBD identified in 1.1

Secondary Objectives - Phase II

To evaluate time to progression, the progression-free survival and overall survival for patients treated with GFL (+/- BV)
To evaluate the early response rate to GFL at 8 weeks
To evaluate the toxicity of GFL (+/- BV)
To evaluate pharmacokinetics of (a) 5-FU and (b) IFN-γ
To evaluate the level of Fas expression in PBMC after IFN-γ administration

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Metastatic colorectal cancer, histologically or cytologically confirmed
Age 18 or greater
Adequate hematologic function (ANC > 1500, hemoglobin > 10 g/dl, platelet count > 100,000)
Adequate hepatic parameters (bilirubin < 2.0, Alk. Phos < 5 times normal, ALT < 5 times normal)
Adequate renal function (creatinine < 2.0)
Performance status ECOG 0-2
0-2 prior lines of chemotherapy for metastatic colorectal cancer are allowed. Prior 5-FU/LV or capecitabine allowed either in the adjuvant setting, or in the metastatic setting or both.
Absence of other serious concurrent medical illnesses
Evaluable or measurable disease for phase I; measurable disease only for phase II

Exclusion Criteria:

Histologies other than adenocarcinoma
Previous grade 4 toxicity to 5-FU +/- LV or capecitabine
Uncontrolled brain metastases
Chronic diarrhea (greater than five bowel movements per day)
Previous chemotherapy or radiation therapy less than 4 weeks prior to study day 1 (less than 6 weeks for chemotherapy with Mitomycin or nitrosoureas)
Major surgery within 2 weeks before study entry
Known allergic sensitivity to leucovorin
Prior exposure to IFN-γ
Previous hematopoietic growth factor (e.g. epoetin alfa or darbepoietin less than 2 weeks prior to study day 1)
Pregnancy or breast feeding. Women of child-bearing potential must have a negative pregnancy test before the first dose.
Other co-existing malignancies or malignancies diagnosed within the last 5 years, with the exception of basal cell carcinoma or cervical cancer in situ
Inability to provide written and informed consent
Uncontrolled hypertension
History of deep venous thrombosis or CVA
Prior exposure to bevacizumab
Proteinuria > 500 mg/24 hr

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00786643

Locations

United States, Tennessee
The West Clinic
Memphis, Tennessee, United States, 38120

Sponsors and Collaborators

Accelerated Community Oncology Research Network

InterMune

More Information

Responsible Party:	Accelerated Community Oncology Research Network ( Amanda Epperson RN, CCRC )
Study ID Numbers:	WITMMCC0301
Study First Received:	November 3, 2008
Last Updated:	November 5, 2008
ClinicalTrials.gov Identifier:	NCT00786643
Health Authority:	United States: Food and Drug Administration

Keywords provided by Accelerated Community Oncology Research Network:

Gamma Interferon
5-FU/LV
The first phase of the trial is designed to find a safe biologically active
dose (SBD) of the GFL combination.

Once the SBD of the combination is established, patients will be
enrolled in the efficacy portion of the trial.
Patients will be stratified by line of therapy for purposes
of response analysis.

Study placed in the following topic categories:

Digestive System Neoplasms
Interferon Type II
Gastrointestinal Diseases
Interferons
Colonic Diseases
Leucovorin
Bevacizumab
Intestinal Diseases
Rectal Diseases
Intestinal Neoplasms
Carcinoma
Tranilast

Folic Acid
Calcium, Dietary
Methamphetamine
Sodium phosphate
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms
Amphetamine
Colorectal Neoplasms
Interferon-gamma, Recombinant
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Vitamin B Complex
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Angiogenesis Inhibitors

Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Vitamins
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Micronutrients

ClinicalTrials.gov processed this record on January 16, 2009