Phase I/II Study of Celebrex and EPO906 in Patients With Metastatic Colorectal Cancer

NCT00159484 | Completed Phase 1 Results DMC

• 1 other identifier: 3c-03-19
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colon Cancer; Colorectal Cancer

Keywords

phase 1; phase one; phase I

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Celebrex in Combination With EPO906

  To determine the maximum tolerated dose (MTD) of Celebrex in combination with EPO906 in patients with metastatic colorectal cancer. The MTD is the highest dose that produces the desired therapeutic effect without causing unacceptable or dose-limiting side effects.

  One month

• Incidence of Grade 3-4 Diarrhea

  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.

  Until 30 days after patient receives last study drug, up to 17 months

Secondary Outcomes (5)

• Overall Survival Rate

  Until Patient goes off study, up to 30 months

• Toxicity (DLTs)

  Through study completion, up to 30 months

• Molecular Biomarkers in Tumor Tissue Associated With Clinical Outcome for This Regimen.

  Until Patient Death

• Progression-Free Survival Rate

  Until patient death, up to 30 months

• Overall Tumor Response Rate

  at baseline and every 2 cycles; up to 30 months

Other Outcomes (1)

• Number of Participants With DLTs in Phase II

  3 weeks

Study Arms (11)

Phase I, Dose Level 1

EXPERIMENTAL

EPO906 7mg in combination with celecoxib

Drug: EPO906; Drug: Celecoxib

Phase I, Dose Level II

EXPERIMENTAL

EPO906 8mg in combination with celecoxib

Drug: EPO906; Drug: Celecoxib

Phase I, Dose Level Ia

EXPERIMENTAL

EPO906 7mg in combination with celecoxib

Drug: EPO906; Drug: Celecoxib

Phase I, Dose Level IIa

EXPERIMENTAL

EPO906 8mg in combination with celecoxib

Drug: EPO906; Drug: Celecoxib

Phase I, Dose Level IIIa

EXPERIMENTAL

EPO906 9mg in combination with celecoxib

Drug: EPO906; Drug: Celecoxib

Phase I, Dose Level IVa

EXPERIMENTAL

EPO906 10mg in combination with celecoxib

Drug: EPO906; Drug: Celecoxib

Phase I, Dose Level Va

EXPERIMENTAL

EPO906 11mg in combination with celecoxib

Drug: EPO906; Drug: Celecoxib

Phase I, Dose Level VIa

EXPERIMENTAL

EPO906 12mg in combination with celecoxib

Drug: EPO906; Drug: Celecoxib

Phase I, Dose Level VIIa

EXPERIMENTAL

EPO906 13mg in combination with celecoxib

Drug: EPO906; Drug: Celecoxib

Phase II, Dose Level Va

EXPERIMENTAL

EPO906 11mg in combination with celecoxib

Drug: EPO906; Drug: Celecoxib

Phase II, Dose Level IIIa

EXPERIMENTAL

EPO906 9mg in combination with celecoxib

Drug: EPO906; Drug: Celecoxib

Interventions

EPO906 DRUG

EPO906 IV, every three weeks

Also known as: epothilone B, EpoB

Phase I, Dose Level 1; Phase I, Dose Level II; Phase I, Dose Level IIIa; Phase I, Dose Level IIa; Phase I, Dose Level IVa; Phase I, Dose Level Ia; Phase I, Dose Level VIIa; Phase I, Dose Level VIa; Phase I, Dose Level Va; Phase II, Dose Level IIIa; Phase II, Dose Level Va

Celecoxib DRUG

celecoxib by mouth twice a day every day

Also known as: Celebrex, Elyxyb, Celebra, Celaxib, Celexi, Onsenal, Vyscoxa

Phase I, Dose Level 1; Phase I, Dose Level II; Phase I, Dose Level IIIa; Phase I, Dose Level IIa; Phase I, Dose Level IVa; Phase I, Dose Level Ia; Phase I, Dose Level VIIa; Phase I, Dose Level VIa; Phase I, Dose Level Va; Phase II, Dose Level IIIa; Phase II, Dose Level Va

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Southern California: lead
• Novartis: collaborator

Study Sites (1)

U.S.C./Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Colorectal Neoplasms

Interventions

epothilone B; Celecoxib

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)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Tali Homsey
• Organization: USC/Norris Comprehensive Cancer Center

tali.homsey@med.usc.edu

(323) 865-0451

Study Officials

• Heinz-Josef Lenz, M.D.

  U.S.C/Norris Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Study Start: October 12, 2004
• Primary Completion: January 13, 2015
• Study Completion: March 23, 2023
• Last Updated: May 28, 2026
• Results First Posted: May 28, 2026

Record last verified: 2025-10

Locations

US (1)