Phase I/II Study of Celebrex and EPO906 in Patients With Metastatic Colorectal Cancer - Full Text View

Sponsor:	USC/Norris Comprehensive Cancer Center
Collaborator:	Novartis
Information provided by (Responsible Party):	USC/Norris Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00159484

Purpose

This study is for people with advanced colorectal cancer. This study uses the drugs Celebrex and EPO906. EPO906 is an experimental drug that has not been approved by the FDA. EPO906 is a drug that has been shown in the laboratory to cause cancer cells to die and prevents them from growing and reproducing. Celebrex is a drug that is approved by the FDA for the treatment of arthritis and prevention of colon polyps. Colon polyps are small growths in the colon. If not surgically removed, some colon polyps can become cancerous. Some studies have shown that Celebrex may reduce the side effects of chemotherapy. Other studies have shown that it may increase the effectiveness of some chemotherapy. Celebrex is not approved by the FDA for reducing the side effects of chemotherapy or improving the effectiveness of chemotherapy. The combination of EPO906 and Celebrex in this study is experimental.

The main goal of this study is to see if adding the drug Celebrex to the drug EPO906 will decrease the amount of diarrhea seen in patients that receive EPO906.

The goal of the first phase of this study is to find the highest dose of EPO906 that can be given safely with Celebrex. The dose of Celebrex will remain the same for the whole study. Higher doses of EPO906 will be given to each group of patients. The increase of EPO906 will stop once more than one patient has serious side effects. The highest dose of EPO906 that can be given with Celebrex (without serious side effects) will be called the pilot dose.

The goal of the second phase of this study is to find out how tumors respond to these doses of the drugs. Another purpose of this study is to see how the body processes the EPO906 and Celebrex. This study will also look at the side effects of these drugs. In this study, we will measure how long subjects live, how often tumors shrink after receiving the study drugs, and how long it takes for tumors to increase in size after receiving the study drugs. This study will also measure the levels of genes, which are the cell's blueprint, in participant's tumors. Several genes can affect how people's bodies react to the cancer drugs. Genes will also be measured in participant's blood. We want to see if these predict response to the study drugs.

Condition	Intervention	Phase
Colon Cancer Colorectal Cancer	Drug: EPO906, celecoxib	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I/II Study of Celebrex and EPO906 in Patients With Metastatic Colorectal Cancer (CEPO906AUS10)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer Diarrhea

Drug Information available for: Epothilone B Celecoxib

U.S. FDA Resources

Further study details as provided by USC/Norris Comprehensive Cancer Center:

Primary Outcome Measures:

To determine the maximum tolerated dose (MTD) of Celebrex in combination with EPO906 in patients with metastatic colorectal cancer. [ Time Frame: One month ] [ Designated as safety issue: Yes ]
Once MTD is established we propose to expand the dose level of the MTD to 62 new patients to evaluate whether the addition of Celebrex to EPO906 can reduce the incidence of grade 3-4 diarrhea to 6% or less. [ Time Frame: Until 30 days after patient receives last study drug ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To estimate the time to progression, survival and response rate in patients with metastatic colorectal cancer who failed 5-FU/LV, CPT-11 and/or oxaliplatin based hemotherapy and receive Celebrex in combination with EPO906. [ Time Frame: Until Patient goes off study ] [ Designated as safety issue: No ]
To further assess toxicity of this regimen. [ Time Frame: 30 days after patient receives last dose ] [ Designated as safety issue: Yes ]
To investigate whether the molecular biomarkers including protein expression changes from plasma, the expression levels of VEGF, E-cadherin, TP, COX-2, and β-tubulin in tumor tissue associated with clinical outcome for this regimen. [ Time Frame: Until Patient Death ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	80
Study Start Date:	October 2004
Estimated Study Completion Date:	January 2013
Estimated Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A EPO906, celecoxib	Drug: EPO906, celecoxib EPO906 IV, every three weeks, celecoxib by mouth twice a day every day

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically confirmed metastatic adenocarcinoma of the colon or rectum for which no further standard chemotherapy is considered to be effective. Patients must have failed 5-FU, CPT-11 and/or oxaliplatin based chemotherapy.
SWOG performance status 0-1
ANC>1000, platelets >100,000.
Total bilirubin < 2 x upper limit of normal. Transaminase (AST and/or ALT) < 2 x upper limit of normal or < 5 x upper limit of normal in patients with liver metastasis.
Serum creatinine < 1.25 x institutional upper limit of normal.
Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing.

Exclusion Criteria:

Patient has received any other investigational agent within 28 days of first day of study drug dosing.
History of another malignancy within 3 years prior to study entry, except curatively treated non-melanoma skin cancer, prostate cancer, or cervical cancer in situ.
Patient has another severe and/or life-threatening medical disease.
Patient has an acute or known chronic liver or kidney disease (e.g., chronic active hepatitis, cirrhosis, chronic renal insufficiency).
Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
Patient has received chemotherapy within 4 weeks (6 weeks for nitrosourea, mitomycin-C or any antibody therapy)
Patients with symptomatic brain metastasis.
Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (e.g. congestive heart failure, myocardial infarction within 6 months of study)
Medical, social or psychological factors interfering with compliance.
Patients who have undergone major surgery for any cause less than 4 weeks prior to study entry.
Patients taking Coumadin® or other agents containing warfarin, with the exception of low dose Coumadin® (1 mg or less) administered prophylactically for maintenance of in-dwelling lines or ports.
Any peripheral neuropathy > Grade 1.
Patients with unresolved diarrhea > Grade 1.
Patients may not have a history of an allergy to sulfonamide drugs.
Patients may not have active peptic ulcer disease or other contraindications to chronic NSAID use or aspirin use.
Patients with lactose intolerance.
Patients taking full-dose NSAIDs, including aspirin, regularly for any reason (e.g., arthritis,history of TIA or myocardial infarction). Patients taking cardiac preventive dose ASA (<81mg daily) are eligible. Patients should stop taking any other NSAIDs 14 days prior to receiving first dose of Celecoxib.
Patients with hypersensitivity to COX-2 inhibitors, NSAIDS or salycilate.
Patients taking fluconazole or lithium.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00159484

Locations

United States, California
U.S.C./Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033

Sponsors and Collaborators

USC/Norris Comprehensive Cancer Center

Novartis

Investigators

Principal Investigator:

Heinz-Josef Lenz, M.D.

U.S.C/Norris Cancer Center

More Information

No publications provided

Responsible Party:	USC/Norris Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00159484 History of Changes
Other Study ID Numbers:	3c-03-19
Study First Received:	September 8, 2005
Last Updated:	December 9, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by USC/Norris Comprehensive Cancer Center:

phase 1
phase one
phase I

Additional relevant MeSH terms:

Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Epothilone B
Celecoxib
Tubulin Modulators

Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012