Cetuximab & Celecoxib for Metastatic Colorectal Cancer or Colorectal Cancer That Cannot Be Removed by Surgery

NCT00466505 | Completed Phase 2 Results DMC

• 4 other identifiers: VICC GI 0410P30CA068485VU-VICC-GI-0410VU-IRB-040227
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cetuximab together with celecoxib may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cetuximab together with celecoxib works in treating patients with metastatic colorectal cancer or colorectal cancer that cannot be removed by surgery.

Conditions

Colorectal Cancer

Keywords

recurrent colon cancer; stage IV colon cancer; recurrent rectal cancer; stage IV rectal cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Number of days from study enrollment to evidence of progressive disease radiographically, with progression defined under RECIST criteria as at least 20% increase in sum of longest diameter of target lesions

  On study date to off study date in this study with median 9.76 months

Secondary Outcomes (8)

• Patient Response to Treatment

  On study date to off study date in this study with median 9.76 months

• Overall Survival

  On study date to off study date in this study with median 9.76 months

• One Year Survival Rate

  1 year from on-study date

• Number of Patients With Each Worst-grade Toxicity Response

  On study date to off study date in this study with median 9.76 months

• Urinary PGE-M : Treatment Cycle 1

  on-study week 5

Study Arms (1)

Therapeutic Intervention

EXPERIMENTAL

Biological: cetuximab; Drug: celecoxib; Genetic: proteomic profiling; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Other: mass spectrometry

Interventions

cetuximab BIOLOGICAL

400 mg/m2 iv week 1, then 250 mg/m2 weekly thereafter, starting on day 1 and continuing until progressive disease, excessive toxicity or removal from study for other reasons listed in the protocol.

Also known as: Erbitux, IMC-C225

Therapeutic Intervention

celecoxib DRUG

200 mg po BID starting on day 1 and continuing until progressive disease, excessive toxicity or removal from study for other reasons listed in the protocol.

Also known as: celebrex

Therapeutic Intervention

proteomic profiling GENETIC

Serum samples obtained as above will be analyzed by proteomic analysis in order to determine biomarkers of treatment response and toxicity prediction. We will use LC-MS-MS or MALDITOF mass spectrometry.

Therapeutic Intervention

immunohistochemistry staining method OTHER

phospho-EGFR levels using western blots of tissue extracts and immunohistochemistry on frozen and (if no other option available, paraffinembedded tissue sections).

Therapeutic Intervention

laboratory biomarker analysis OTHER

Serum samples obtained as above will be analyzed by proteomic analysis in order to determine biomarkers of treatment response and toxicity prediction.

Therapeutic Intervention

mass spectrometry OTHER

We will use LC-MS-MS or MALDITOF mass spectrometry. Before any tissues are received, the drug of interest is evaluated via MALDI mass spectrometry on a MDS/Sciex QStar QqTOF mass spectrometer.

Therapeutic Intervention

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed colorectal cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \> or equal to 20 mm with conventional techniques or as \> or equal 10 mm with spiral CT scan.
• Patients must have progressed after at least 1 chemotherapy regimen for advanced disease. No prior therapy which specifically and directly targets the EGFR pathway.
• Age 18 years or older
• ECOG performance status ≤ 2.
• Life expectancy of greater than 3 months.
• Normal organ and marrow functions as defined below:
• absolute neutrophil count ≤ 1,500/μl
• platelets ≤ 100,000/μl
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) \> or equal to 2.5 times institutional upper limit of normal or \> or equal to 5.0 times normal if liver metastases are present
• creatinine within normal institutional limits OR
• creatinine clearance \> or equal to 60 mL/min/1.73 m2 for patients creatinine levels above institutional normal
• The effects of cetuximab and/or celecoxib on the developing human fetus at the recommended therapeutic doses are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to provide written informed consent.

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients may not be receiving any other investigational agents.
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Prior severe infusion reaction to a monoclonal antibody
• Serum calcium \>12.0 mg/dl.
• Patients must be off all other selective or non-selective COX-2 inhibitors for at least 2 weeks prior to study entry (with the exception of 81 mg of daily aspirin).
• No major surgery within 4 weeks. No minor surgery (laparoscopy, thoracoscopy, port placement) within 1 week.
• Patients must be \> 4 weeks from prior pelvic radiation and recovered from side effects.
• Patients must be \> 1 week from prior palliative radiation and have recovered from all side effects.
• Prior treatment with EGFR targeting therapies.
• Significant traumatic injury occurring within 28 days prior to treatment.
• Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because cetuximab is an epidermal growth factor inhibitor with the potential for teratogenic or abortifacient effects based on the data suggesting that EGFR expression is important for normal organ development. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cetuximab, breastfeeding should be discontinued if the mother is treated with cetuximab.
• Patients with known HIV disease.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Cetuximab; Celecoxib; Immunohistochemistry; Mass Spectrometry

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; Chemistry Techniques, Analytical

Results Point of Contact

• Title: Jordan Berlin, MD
• Organization: Vanderbilt-Ingram Cancer center

jordan.berlin@vanderbilt.edu

615-343-4128

Study Officials

• Jordan D. Berlin, MD

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Jordan Berlin, MD

Study Record Dates

• First Submitted: April 25, 2007
• First Posted: April 27, 2007
• Study Start: May 1, 2005
• Primary Completion: July 1, 2008
• Study Completion: November 1, 2008
• Last Updated: December 19, 2012
• Results First Posted: November 16, 2011

Record last verified: 2012-12

Locations

US (1)