- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00226941
A Phase 1-2 Trial of Cetuximab in Combination With Oxaliplatin, Capecitabine, and Radiation Therapy Followed by Surgery for Locally-advanced Rectal Cancer
A Phase 1-2 Trial of Cetuximab in Combination With Oxaliplatin, Capecitabine, and Radiation Therapy Followed by Surgical Resection for Locally-Advanced Rectal Cancer
The objectives of this study are to:
- To assess dose-limiting toxicities (DLTs) of capecitabine +/- oxaliplatin in a combination regimen with capecitabine and radiotherapy (Phase 1)
To determine the maximum-tolerated dose (MTD) when capecitabine
- oxaliplatin in a combination regimen with capecitabine and radiotherapy (Phase 1)
- To determine the pathologic response rate of cetuximab +/- oxaliplatin in combination with capecitabine and radiotherapy (Phase 2)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Part of the treatment plan for this study is surgical removal of the tumor that is planned to occur 6 to 8 weeks after completion of radiotherapy (XRT). This study consists of 2 distinct phases (Phase 1 and Phase 2).
In Phase 1, the objectives are to
- Assess dose-limiting toxicities (DLTs) and
- Determine a maximum-tolerated dose (MTD)
The Phase 1 endpoints are assessed on an initial cohort of patients after the completion of the chemo-radiotherapy regimen at defined timepoints that precede surgery.
Phase 2 is the efficacy assessment portion of this study. In Phase 2, the objective is to accrue an expansion cohort. Efficacy assessments for phase 2 are to be assessed across all study participants at the time of, or after, surgery, as measured by the pathologic response rate; downstaging; and survival at 5 years from the start of treatment.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Stanford, California, United States, 94305
- Stanford University School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
INCLUSION CRITERIA
- Histologically-confirmed adenocarcinoma of the rectum. Clinical stages T3; T4; or N1 as determined by endoscopic ultrasound; or a rectal CT or MRI scan are eligible, including T3 N0; T3 N1; T4 N0; T4 N1; T1-4 N1. Rectal cancers are defined as those whose distal border extends to within 12 cm of the anal verge.
- Age ≥ 18
- Karnofsky performance status (KPS) ≥ 70
- Leukocyte count > 3,500 x 10e6/µL
- Platelet count > 100,000/µL
- Serum glutamic-oxaloacetic transaminase (SGOT) < 2.5 x institutional upper limits of normal (ULN)
- Serum glutamic-pyruvic transaminase (SGPT) < 2.5 x ULN
- Alkaline phosphatase < 2.5 x ULN
- Total bilirubin < 1.5x ULN
Creatinine:
- Within normal institutional limits
- OR
- Creatinine clearance > 60 mL/min/1.73 m2 (if serum creatinine levels above institutional normal)
- Ability to swallow pills without difficulty
- Women of child-bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG), within 72 hours prior to the start of study medication
- Women of child-bearing potential must be using an adequate method of contraception to avoid pregnancy throughout the treatment
EXCLUSION CRITERIA
- Metastatic (M1) or stage IV disease
- Prior history of treatment with cetuximab or other therapy targeting EGFR
- Prior history of anti-cancer murine monoclonal antibody therapy
- Prior pelvic or whole abdominal radiotherapy
Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness / social situations that would limit compliance with study requirements
- Patients with a concurrent malignancy or previous malignancy within 5 years of screening will be excluded from this study (EXCEPTION: concurrent or previous non-melanoma skin cancer, hematolymphoid malignancy or carcinoma in-situ of the cervix may be allowed at the investigator's discretion)
- Inability to sign written consent
- Pregnant or breastfeeding
- Unwilling or unable to use effective contraception in self or partner for the entire study period and for up to 4 weeks after the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group 1 - Cetuximab + Capecitabine-800 + XRT + Oxaliplatin-100
|
Cetuximab is a chimeric anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, administered via a intravenous (IV) infusion at 400 mg/m² (initial loading dose) or 250 mg/m² (weekly dose).
Dosage is based on m² of body surface area (BSA)
Other Names:
Oxaliplatin is a cancer medication used to treat colorectal cancer, and is administered on Days 2 and 23.
Other Names:
Capecitabine is a cancer medication, and is administered based on m² of body surface area (BSA) delivered in equivalent morning and evening doses
Other Names:
Radiotherapy is administered on weekdays in 180 centigray fractions ("doses"), for 28 total fractions delivering a total dose of 5040 centigray (cGy)
Other Names:
Diphenhydramine HCl 50 mg (or equivalent) is administered as a per-medication for cetuximab
Other Names:
|
Experimental: Group 2 - Cetuximab + Capecitabine-700 + XRT + Oxaliplatin-85
|
Cetuximab is a chimeric anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, administered via a intravenous (IV) infusion at 400 mg/m² (initial loading dose) or 250 mg/m² (weekly dose).
Dosage is based on m² of body surface area (BSA)
Other Names:
Oxaliplatin is a cancer medication used to treat colorectal cancer, and is administered on Days 2 and 23.
Other Names:
Capecitabine is a cancer medication, and is administered based on m² of body surface area (BSA) delivered in equivalent morning and evening doses
Other Names:
Radiotherapy is administered on weekdays in 180 centigray fractions ("doses"), for 28 total fractions delivering a total dose of 5040 centigray (cGy)
Other Names:
Diphenhydramine HCl 50 mg (or equivalent) is administered as a per-medication for cetuximab
Other Names:
|
Experimental: Group A - Cetuximab + Capecitabine-800 + XRT
|
Cetuximab is a chimeric anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, administered via a intravenous (IV) infusion at 400 mg/m² (initial loading dose) or 250 mg/m² (weekly dose).
Dosage is based on m² of body surface area (BSA)
Other Names:
Capecitabine is a cancer medication, and is administered based on m² of body surface area (BSA) delivered in equivalent morning and evening doses
Other Names:
Radiotherapy is administered on weekdays in 180 centigray fractions ("doses"), for 28 total fractions delivering a total dose of 5040 centigray (cGy)
Other Names:
Diphenhydramine HCl 50 mg (or equivalent) is administered as a per-medication for cetuximab
Other Names:
|
Experimental: Group B - Cetuximab + Capecitabine-1000 + XRT
|
Cetuximab is a chimeric anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, administered via a intravenous (IV) infusion at 400 mg/m² (initial loading dose) or 250 mg/m² (weekly dose).
Dosage is based on m² of body surface area (BSA)
Other Names:
Capecitabine is a cancer medication, and is administered based on m² of body surface area (BSA) delivered in equivalent morning and evening doses
Other Names:
Radiotherapy is administered on weekdays in 180 centigray fractions ("doses"), for 28 total fractions delivering a total dose of 5040 centigray (cGy)
Other Names:
Diphenhydramine HCl 50 mg (or equivalent) is administered as a per-medication for cetuximab
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose-limiting Toxicity (DLT) - Number of DLTs by Treatment Group
Time Frame: 10 weeks
|
Dose-limiting Toxicity (DLT) is the measure used to establish overall Maximum-tolerated dose (MTD) of cetuximab + capecitabine + radiotherapy +/- oxaliplatin.
MTD is defined as the highest dose level for which participants have a < 30% incidence of dose-limiting toxicity (DLT).
The outcome is expressed as the number of DLTs by treatment group.
|
10 weeks
|
Dose-limiting Toxicity (DLT) - Number of Participants Affected
Time Frame: 10 weeks
|
Dose-limiting Toxicity (DLT) is the measure used to establish overall Maximum-tolerated dose (MTD) of cetuximab + capecitabine + radiotherapy +/- oxaliplatin.
MTD is defined as the highest dose level for which participants have a < 30% incidence of dose-limiting toxicity (DLT).
The outcome is expressed as the number of participants experiencing a DLT.
|
10 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pathologic Response Rate
Time Frame: 12 to 14 weeks after radiotherapy
|
After treatment with capecitabine, cetuximab, radiotherapy, and oxaliplatin, the pathologic response rate was assessed based on the excised tumor taken at the time of surgical resection.
Pathologic response rate was determined as the number and proportion of participants who experienced either downstaging of their disease, or complete response (CR, no detectable disease).
A participant will be considered to have downstaging of the tumor as a result of the neoadjuvant therapy when the primary tumor (T) stage by pathology isless than the T stage by clinical (endoscopic) evaluation, or when the regional lymph node (N) tumor stage by pathology is less than the N stage by clinical (endoscopic) evaluation.
|
12 to 14 weeks after radiotherapy
|
Tumor Downstaging at Surgical Resection
Time Frame: 12 to 14 weeks after radiotherapy
|
Downstaging means a reduction from the stage of disease observed at baseline to the stage of disease after treatment with cetuximab, radiotherapy, oxaliplatin, and capecitabine, as determined at the time of surgical removal of the tumor.
Downstaging may be observed as improvements in tumor staging at the primary site of the tumor; in nearby (regional) lymph nodes; or in metastatic disease beyond the regional lymph nodes.
This outcome specifically does not include participants that achieved a complete response, nor those that experienced no response or disease progression.
|
12 to 14 weeks after radiotherapy
|
Time-to-Progression (TTP)
Time Frame: 5 years
|
Time-to-progression was assessed as the time from the date of surgical resection to the appearance of either local disease recurrence or distant metastases by any modality (eg, clinical exam, endoscopy, radiographic imaging).
All relapses were to be confirmed by biopsy and pathology review.
|
5 years
|
Overall Survival (OS)
Time Frame: 72 months
|
Overall Survival (OS) was assessed as the mean survival from the date of entry on study though 72 months.
|
72 months
|
Survival at 5 Years
Time Frame: 5 years
|
Survival at 5 years was assessed as the number of participants alive 5 years after starting treatment.
|
5 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Branimir I Sikic, MD, Stanford University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Rectal Neoplasms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Sensory System Agents
- Anesthetics
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Antineoplastic Agents, Immunological
- Dermatologic Agents
- Hypnotics and Sedatives
- Anesthetics, Local
- Anti-Allergic Agents
- Sleep Aids, Pharmaceutical
- Histamine H1 Antagonists
- Histamine Antagonists
- Histamine Agents
- Antipruritics
- Capecitabine
- Oxaliplatin
- Diphenhydramine
- Promethazine
- Cetuximab
Other Study ID Numbers
- IRB-12426
- COR0001 (Other Identifier: OnCore)
- 95054 (Other Identifier: Stanford IRB, historical)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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