A Study of Amifostine (Ethyol) in Patients With Colorectal Cancer

Phase II Study of the Efficacy of Amifostine (Ethyol) in Reducing the Incidence and Severity of Oxaliplatin-Induced Neuropathy in Patients With Colorectal Cancer

The purpose of this study is to determine the effect of amifostine (ETHYOL) on decreasing the rate and severity of nerve dysfunction or neuropathy (numbness and tingling in hands and feet) associated with FOLFOX chemotherapy.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Amifostine

Detailed Description

In addition, this study will provide information on how subjects with colorectal cancer do while receiving amifostine in combination with other chemotherapy drugs. This study will also look at the frequency of complications associated with amifostine and chemotherapy.

The FOLFOX chemotherapy regimen consists of three drugs, 5-FU, leucovorin, and oxaliplatin, all given intravenously (into the vein) every 2 weeks with or without Avastin given in combination with chemotherapy. FOLFOX has been approved by the Food and Drug Administration (FDA) for the treatment of cancer of the colon or rectum.

Amifostine is not a chemotherapy drug. It is approved by the Food and Drug Administration (FDA) to prevent moderate or severe dryness of the mouth caused by radiation treatment for head and neck cancer, and to prevent kidney damage caused by cisplatin chemotherapy treatment for ovarian and non-small cell lung cancer. Amifostine is not FDA approved for use in this study and is therefore considered investigational.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically-proven adenocarcinoma of the colon or rectum
• AJCC stage II, III or IV
• Male of female aged greater than or equal to 18 years
• ECOG Performance Status (PS): 0-2
• Men or women of reproductive potential must have agreed to use an effective method of contraception while on treatment and for 6 months after study treatment
• If female, not pregnant or lactating. Documentation of a negative serum HCG pregnancy test for women of childbearing potential is required within 7 days prior to be considered of non-childbearing potential
• In the opinion of the investigator, patients must have a life expectancy of least 6 months
• At the time of study enrollment, absolute granulocyte count (AGC) must be greater than or equal to 1500/mm3, platelet count must be greater than or equal to 100,000/mm3
• There must be evidence of adequate hepatic and renal function. Bilirubin less than or equal to UNL, Alkaline phosphatase less than or equal to 2.5xULN, AST less than or equal to 1.5xULN, Creatine less than or equal to 1.5xULN
• Signed written informed consent obtained prior to study-specific screening procedure

Exclusion Criteria:

• Any condition or past medical history that contra-indicate treatment with oxaliplatin and 5FU, as reported in the approval labeling information
• Hypersensitivity to any of the study treatments (amifostine, oxaliplatin and 5FU) or ingredients
• Received any investigational drug within 30 days before beginning treatment with study drug
• Concomitant treatment with other investigational agents
• Received prior oxaliplatin or cisplatin based chemotherapy
• History of peripheral neuropathy
• concomitant treatments with drugs/ingredients reported to have a potential activity in preventing peripheral sensory neuropathy: carbamazepine, gabapentin, phenytoin, gluthathione, alpha-lipoic acid, celecoxib, venlafaxine, vitamin B1 (thiamine), B6 (pyridoxine), ginko biloba. Multivitamins and dietary supplements are allowed. Uncontrolled intercurrent illness: e.g. high blood pressure, unstable angina, symptomatic congestive hear failure (NY Heart Association Classification III or IV), serious cardiac arrhythmia, diabetes, or active infection
• Concurrent active cancer originating from a primary site other than colon or rectum
• Presence of any symptom suggesting brain/spinal cord metastasis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment Period; The chemotherapy regimen will be given for 2 consecutive days. On day #1, pt. will be premedicated with drugs to prevent nausea and vomiting in addition to intravenous fluids. Then they will receive amifostine intravenously followed by oxaliplatin, 5FU and leucovorin. This will be followed by an infusion of 5FU given in a pump over 22 hours. If the doctor decides on giving the pt. Avastin, this will be given on day #1. On day #2, they will receive the same treatment except for oxaliplatin.

Drug: Amifostine; Patients should be treated with oxaliplatin-based chemotherapy in combination with amifostine for 12 cycles, or until unacceptable toxicity is observed or disease progression; Other Names: Bevacizumab; Oxaliplatin; Flurouracil (5-FU); Leucovorin calcium (LV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Test Drug in 28 Patients and Assess PSN. If 5 or More Have Grade 3 & 4 PSN, Trial Will be Terminated.	There were only four participants in this study. None of which completed the questionnaires needed to assess this outcome. This study was closed by the sponsor on January 13, 2010 due to low enrollment.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess PSN in 69 Patients. If Total Number of Cumulative PSN is > or Equal to 14, Drug Will be Rejected.	There were only four participants in this study. None of which completed the questionnaires needed to assess this outcome. This study was closed by the sponsor on January 13, 2010 due to low enrollment.	1 year

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: AstraZeneca; MedImmune LLC
• Investigators: Study Director: Michelle Marcum, University of Cincinnati

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): January 13, 2010
• Study Completion (Actual): January 13, 2010

Study Registration Dates

• First Submitted: January 14, 2008
• First Submitted That Met QC Criteria: January 24, 2008
• First Posted (Estimated): January 25, 2008

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Oxaliplatin-induced Neuropathy; Colon and rectum
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Radiation-Protective Agents; Oxaliplatin; Leucovorin; Levoleucovorin; Amifostine
• Other Study ID Numbers: ETH190-06