Phase II Trial of Neoadjuvant FOLFOX4 and Cetuximab for Localized Adenocarcinoma of Rectum

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00580073
• Collaborator: Sanofi (Industry), Bristol-Myers Squibb (Industry), Eli Lilly and Company (Industry)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 23
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study involves the use of Oxaliplatin, 5-Fluorouracil (5-FU), Leucovorin and Cetuximab, which are all medicines approved by the Food and Drug Administration (FDA) and are commercially available. This treatment regimen will possibly be combined with radiation before and/or after surgery depending on your response to the treatment. Their use in this exact combination is considered experimental. The purpose of this study is to find out how effective this combination of chemotherapy is as treatment for rectal cancer that has not spread to other parts of the body. The side effects and survival experienced by subjects receiving these drugs will also be evaluated. This is a phase II research study.

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer	Drug: FOLFOX4; Drug: Cetuximab	Phase 2

Detailed Description

Primary Objective:

• Down-staging of the tumor

Secondary Objectives:

• Pathologic response rate

• Tumor marker response

• Incidence of sphincter sparing surgery

• Progression-free survival

• Overall Survival

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Neoadjuvant FOLFOX4 and Cetuximab for Localized Adenocarcinoma of the Rectum
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 1 FOLFOX4 + Cetuximab

Drug: FOLFOX4; oxaliplatin (85mg/m2 on days 1 and 15 of each cycle)+ 5FU Bolus (400mg/m2 on days 1, 2, 15, and 16 of each cycle) + 5FU CI (600mg/m2 on days 1, 2, 15, and 16 of each cycle) + Leucovorin (200mg/m2 on days 1, 2, 15, and 16 of each cycle); Other Names: Oxaliplatin (Eloxatin), 5FU (5-Fluorouracil) and Leucovorin (Folinic Acid) ; Drug: Cetuximab; Cetuximab 400mg/m2 on day 1 only, 250mg/mr on days 8, 15, and 22 of each cycle.; Other Names: Cetuximab (C225, Erbitux)

Outcome Measures

Primary Outcome Measures

1. Down-staging of the Tumor; Response to Therapy [6 months]

   Down-staging of the tumor and tumor response rate is defined as the proportion of participant who have any evidence of complete response (CR), pathologic complete response (pCR), or partial response (PR).

Secondary Outcome Measures

1. Progression Free Survival [Up to 3 years]

   Number of participants who achieve progression free survival, defined as the time from date of registration to date of disease progression, up through study closure. Progressive disease is defined as ≥ 20% increase in the sum of the longest dimensions of the primary lesion taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.

2. Overall Survival [Up to 3 years]

   Overall survival is defined as the time from date of registration to date of death. In the absence of confirmation of death, survival time will be censored at the last date of follow-up.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All patients must have newly diagnosed, histologically proven adenocarcinoma of the rectum. Locally advanced T3, T4 or any T with N1, N2, staged by trans-rectal ultrasound.

• All patients must have an abdominal/pelvis CT scan or MRI confirming no evidence of distant metastases.

• Patients must have an ECOG PS ≤ 2

• Patient has signed informed consent

• Lower Age Limit: 18 years

• Upper Age Limit: No upper age limit

• Laboratory parameters:

• Hgb: > 9.0 g/dl

• ANC >1500/ul

• Platelet >100,000/ul

• Creatinine < 2x ULN

• Bilirubin < 2x ULN

• ALT < 2x ULN

Exclusion Criteria:

• Administration of any prior systemic anticancer therapy for colorectal cancer (eg, chemotherapy, antibody therapy, immunotherapy, gene therapy, vaccine therapy, cytokine therapy, angiogenesis inhibitors).

• Previous intra-arterial cytotoxic chemotherapy given as treatment for colorectal cancer.

• Previous pelvic radiotherapy.

• Known allergy or intolerance to oxaliplatin, 5-FU, cetuximab or leucovorin.

• Pregnant or breast-feeding women: female patients must agree to use effective contraception, must be surgically sterile, or must be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. All at-risk female patients must have a negative serum pregnancy test within 7 days prior to registration.

• Active inflammatory bowel disease, significant bowel obstruction, or chronic diarrhea (grade 2).

• Myocardial infarction or stroke within the previous 6 months, or ongoing unstable angina, symptomatic congestive heart failure, or serious uncontrolled cardiac dysrhythmia.

• Known human immunodeficiency virus (HIV) positivity or acquired-immunodeficiency-syndrome (AIDS)-related illness.

• No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer for which the patient has been disease-free for 3 years.

• Known CNS metastases

• Preexisting neuropathy > Grade 2

• Prior therapy which specifically and directly targets the EGFR pathway

• Prior severe infusion reaction to a monoclonal antibody

• Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure and cardiomyopathy with decreased ejection fraction.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• University of Wisconsin, Madison
• Sanofi
• Bristol-Myers Squibb
• Eli Lilly and Company

Investigators

• Study Chair: Michael Huie, M.D., UW Paul P. Carbone Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT00580073
• Other Study ID Numbers: CO06207; NCI-2011-00476; A534260; SMPH/MEDICINE; H-2007-0197
• First Posted: Dec 24, 2007
• Last Update Posted: Dec 13, 2019
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Adenocarcinoma; Leucovorin; Fluorouracil; Oxaliplatin; Cetuximab

Study Results

Participant Flow

Recruitment Details	Participants were enrolled between 4/08 and 11/09 from a large cancer research institution.

Arm/Group Title	FOLFOX4 + Cetuximab
Arm/Group Description	FOLFOX4: oxaliplatin (85mg/m2 on days 1 and 15 of each cycle)+ 5FU (5-fluorouracil) Bolus (400mg/m2 on days 1, 2, 15, and 16 of each cycle) + 5FU CI (600mg/m2 on days 1, 2, 15, and 16 of each cycle) + Leucovorin (200mg/m2 on days 1, 2, 15, and 16 of each cycle) Cetuximab: Cetuximab 400mg/m2 on day 1 only, 250mg/mr on days 8, 15, and 22 of each cycle.
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	FOLFOX4 + Cetuximab
Arm/Group Description	FOLFOX4: oxaliplatin (85mg/m2 on days 1 and 15 of each cycle)+ 5FU Bolus (400mg/m2 on days 1, 2, 15, and 16 of each cycle) + 5FU CI (600mg/m2 on days 1, 2, 15, and 16 of each cycle) + Leucovorin (200mg/m2 on days 1, 2, 15, and 16 of each cycle) Cetuximab: Cetuximab 400mg/m2 on day 1 only, 250mg/mr on days 8, 15, and 22 of each cycle.
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 50%
>=65 years	3 50%
Sex: Female, Male (Count of Participants)
Female	4 66.7%
Male	2 33.3%
Region of Enrollment (participants) [Number]
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Down-staging of the Tumor; Response to Therapy
Description	Down-staging of the tumor and tumor response rate is defined as the proportion of participant who have any evidence of complete response (CR), pathologic complete response (pCR), or partial response (PR).
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FOLFOX4 + Cetuximab
Arm/Group Description	FOLFOX4: oxaliplatin (85mg/m2 on days 1 and 15 of each cycle)+ 5FU Bolus (400mg/m2 on days 1, 2, 15, and 16 of each cycle) + 5FU CI (600mg/m2 on days 1, 2, 15, and 16 of each cycle) + Leucovorin (200mg/m2 on days 1, 2, 15, and 16 of each cycle) Cetuximab: Cetuximab 400mg/m2 on day 1 only, 250mg/mr on days 8, 15, and 22 of each cycle.
Measure Participants	6
PR	4 66.7%
pCR	1 16.7%
CR	0 0%

2. Secondary Outcome

Title	Progression Free Survival
Description	Number of participants who achieve progression free survival, defined as the time from date of registration to date of disease progression, up through study closure. Progressive disease is defined as ≥ 20% increase in the sum of the longest dimensions of the primary lesion taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FOLFOX4 + Cetuximab
Arm/Group Description	FOLFOX4: oxaliplatin (85mg/m2 on days 1 and 15 of each cycle)+ 5FU Bolus (400mg/m2 on days 1, 2, 15, and 16 of each cycle) + 5FU CI (600mg/m2 on days 1, 2, 15, and 16 of each cycle) + Leucovorin (200mg/m2 on days 1, 2, 15, and 16 of each cycle) Cetuximab: Cetuximab 400mg/m2 on day 1 only, 250mg/mr on days 8, 15, and 22 of each cycle.
Measure Participants	6
Number [participants]	5 83.3%

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the time from date of registration to date of death. In the absence of confirmation of death, survival time will be censored at the last date of follow-up.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

This study was closed because of withdrawal of funding. All participants were off study on 02/03/2011.

Arm/Group Title	FOLFOX4 + Cetuximab
Arm/Group Description	FOLFOX4: oxaliplatin (85mg/m2 on days 1 and 15 of each cycle)+ 5FU Bolus (400mg/m2 on days 1, 2, 15, and 16 of each cycle) + 5FU CI (600mg/m2 on days 1, 2, 15, and 16 of each cycle) + Leucovorin (200mg/m2 on days 1, 2, 15, and 16 of each cycle) Cetuximab: Cetuximab 400mg/m2 on day 1 only, 250mg/mr on days 8, 15, and 22 of each cycle.
Measure Participants	0

Adverse Events

Time Frame	Adverse event data were collected from Day 0 of treatment through the Study Completion Date (02/03/2011), which is a time period of up to 3 years.
Adverse Event Reporting Description	Participants were closely monitored for treatment-related adverse events, especially infusion reactions, during the infusion and the post-infusion observation hour. All
Arm/Group Title	FOLFOX4 + Cetuximab
Arm/Group Description	FOLFOX4: oxaliplatin (85mg/m2 on days 1 and 15 of each cycle)+ 5FU Bolus (400mg/m2 on days 1, 2, 15, and 16 of each cycle) + 5FU CI (600mg/m2 on days 1, 2, 15, and 16 of each cycle) + Leucovorin (200mg/m2 on days 1, 2, 15, and 16 of each cycle) Cetuximab: Cetuximab 400mg/m2 on day 1 only, 250mg/mr on days 8, 15, and 22 of each cycle.
All Cause Mortality
	FOLFOX4 + Cetuximab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	FOLFOX4 + Cetuximab
	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)
Blood and lymphatic system disorders
Grade 3/4 neutropenia	3/6 (50%)	3
General disorders
Grade 3/4 fatigue	1/6 (16.7%)	1
Investigations
Grade 3/4 aspartate aminotransferase (AST)	1/6 (16.7%)	1
Grade 3/4 alanine aminotransferase (ALT)	1/6 (16.7%)	1
Metabolism and nutrition disorders
Grade 3/4 potassium, serum-low (hypokalemia)	2/6 (33.3%)	2
Nervous system disorders
Grade 3/4 neuropathy	1/6 (16.7%)	1
Other (Not Including Serious) Adverse Events
	FOLFOX4 + Cetuximab
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Blood and lymphatic system disorders
Grade 1/2 neutropenia	3/6 (50%)	3
Gastrointestinal disorders
Grade 1/2 mucositis	2/6 (33.3%)	2
Grade 1/2 nausea	2/6 (33.3%)	2
Grade 1/2 diarrhea	2/6 (33.3%)	2
General disorders
Grade 1/2 fatigue	3/6 (50%)	3
Investigations
Grade 1/2 aspartate aminotransferase (AST)	1/6 (16.7%)	1
Grade 1/2 alanine transaminase (ALT)	1/6 (16.7%)	1
Metabolism and nutrition disorders
Grade 1/2 potassium, serum-low (hypokalemia)	1/6 (16.7%)	1
Nervous system disorders
Grade 1/2 neuropathy	3/6 (50%)	3
Skin and subcutaneous tissue disorders
Grade 1/2 rash	4/6 (66.7%)	4

Limitations/Caveats

Study closed due to withdrawal of funding.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.