A Phase 1-2 Trial of Cetuximab in Combination With Oxaliplatin, Capecitabine, and Radiation Therapy Followed by Surgery for Locally-advanced Rectal Cancer

NCT00226941 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: IRB-12426COR000195054
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The objectives of this study are to:

1. 1.To assess dose-limiting toxicities (DLTs) of capecitabine +/- oxaliplatin in a combination regimen with capecitabine and radiotherapy (Phase 1)
2. 2.To determine the maximum-tolerated dose (MTD) when capecitabine
3. 3.oxaliplatin in a combination regimen with capecitabine and radiotherapy (Phase 1)
4. 4.To determine the pathologic response rate of cetuximab +/- oxaliplatin in combination with capecitabine and radiotherapy (Phase 2)

Conditions

Rectal Cancer; Colo-rectal Cancer

Outcome Measures

Primary Outcomes (2)

• Dose-limiting Toxicity (DLT) - Number of DLTs by Treatment Group

  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

  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 Outcomes (5)

• Pathologic Response Rate

  12 to 14 weeks after radiotherapy

• Tumor Downstaging at Surgical Resection

  12 to 14 weeks after radiotherapy

• Time-to-Progression (TTP)

  5 years

• Overall Survival (OS)

  72 months

• Survival at 5 Years

  5 years

Study Arms (4)

Group 1 - Cetuximab + Capecitabine-800 + XRT + Oxaliplatin-100

EXPERIMENTAL

* Cetuximab 250 mg/m² / week * Capecitabine 800 mg/m² * Radiotherapy (XRT) * Oxaliplatin 100 mg/m², Days 2 and 23

Drug: Cetuximab; Drug: Oxaliplatin; Drug: Capecitabine; Radiation: Radiotherapy; Drug: Diphenhydramine hydrochloride (HCl)

Group 2 - Cetuximab + Capecitabine-700 + XRT + Oxaliplatin-85

EXPERIMENTAL

* Cetuximab 250 mg/m² / week * Capecitabine 700 mg/m² * Radiotherapy (XRT) * Oxaliplatin 85 mg/m², Days 2 and 23

Drug: Cetuximab; Drug: Oxaliplatin; Drug: Capecitabine; Radiation: Radiotherapy; Drug: Diphenhydramine hydrochloride (HCl)

Group A - Cetuximab + Capecitabine-800 + XRT

EXPERIMENTAL

* Cetuximab 250 mg/m² / week * Capecitabine 800 mg/m² * Radiotherapy (XRT)

Drug: Cetuximab; Drug: Capecitabine; Radiation: Radiotherapy; Drug: Diphenhydramine hydrochloride (HCl)

Group B - Cetuximab + Capecitabine-1000 + XRT

EXPERIMENTAL

* Cetuximab 250 mg/m² / week * Capecitabine 1000 mg/m² * Radiotherapy (XRT)

Drug: Cetuximab; Drug: Capecitabine; Radiation: Radiotherapy; Drug: Diphenhydramine hydrochloride (HCl)

Interventions

Cetuximab DRUG

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)

Also known as: Erbitux, C225, IMC-C225

Group 1 - Cetuximab + Capecitabine-800 + XRT + Oxaliplatin-100; Group 2 - Cetuximab + Capecitabine-700 + XRT + Oxaliplatin-85; Group A - Cetuximab + Capecitabine-800 + XRT; Group B - Cetuximab + Capecitabine-1000 + XRT

Oxaliplatin DRUG

Oxaliplatin is a cancer medication used to treat colorectal cancer, and is administered on Days 2 and 23.

Also known as: Eloxatin

Group 1 - Cetuximab + Capecitabine-800 + XRT + Oxaliplatin-100; Group 2 - Cetuximab + Capecitabine-700 + XRT + Oxaliplatin-85

Capecitabine DRUG

Capecitabine is a cancer medication, and is administered based on m² of body surface area (BSA) delivered in equivalent morning and evening doses

Also known as: Xeloda

Group 1 - Cetuximab + Capecitabine-800 + XRT + Oxaliplatin-100; Group 2 - Cetuximab + Capecitabine-700 + XRT + Oxaliplatin-85; Group A - Cetuximab + Capecitabine-800 + XRT; Group B - Cetuximab + Capecitabine-1000 + XRT

Radiotherapy RADIATION

Radiotherapy is administered on weekdays in 180 centigray fractions ("doses"), for 28 total fractions delivering a total dose of 5040 centigray (cGy)

Also known as: XRT

Group 1 - Cetuximab + Capecitabine-800 + XRT + Oxaliplatin-100; Group 2 - Cetuximab + Capecitabine-700 + XRT + Oxaliplatin-85; Group A - Cetuximab + Capecitabine-800 + XRT; Group B - Cetuximab + Capecitabine-1000 + XRT

Diphenhydramine hydrochloride (HCl) DRUG

Diphenhydramine HCl 50 mg (or equivalent) is administered as a per-medication for cetuximab

Also known as: Benadryl, Unisom, Sominex

Group 1 - Cetuximab + Capecitabine-800 + XRT + Oxaliplatin-100; Group 2 - Cetuximab + Capecitabine-700 + XRT + Oxaliplatin-85; Group A - Cetuximab + Capecitabine-800 + XRT; Group B - Cetuximab + Capecitabine-1000 + XRT

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• George Albert Fisher: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms; Colonic Neoplasms

Interventions

Cetuximab; Oxaliplatin; Capecitabine; Radiotherapy; Diphenhydramine; Doxylamine

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Colonic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics; Ethylamines; Amines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Pyridines

Limitations and Caveats

This trial was halted after the phase 1 portion of enrollment, and before the phase 2 portion accrued. Data reported for phase 2 objectives/outcomes do not include any phase 2 participants, and are only provided for completeness.

Results Point of Contact

• Title: George Albert Fisher, Jr, MD, PhD; Colleen Haas Chair, School of Medicine
• Organization: Stanford Cancer Institute, Stanford University

georgeaf@stanford.edu

650-723-2990

Study Officials

• George A Fisher, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Branimir I Sikic, MD

  Stanford University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine and Colleen Haas Chair in the School of Medicine

Model Details: Sequential design for 4 dose combinations (arms) through phase 1

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 27, 2005
• Study Start: June 1, 2004
• Primary Completion: March 1, 2008
• Study Completion: February 1, 2009
• Last Updated: December 8, 2017
• Results First Posted: December 8, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)