A Study of Combination of Gemcitabine, Oxaliplatin (GEMOX)-Sorafenib in Patients With Advanced Biliary Tract Cancer

NCT00955721 | Terminated Phase 1 Results DMC

• 2 other identifiers: 20090256SCCC-2009003
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to build on the efficacy of the GEMOX regimen by adding Sorafenib in the treatment of Biliary Tract Cancer. Since there is no data on the combination of these three agents, the investigators plan to evaluate the safety in a run-in phase I portion in order to define the recommended phase II dose (RPTD). The phase II trial will enroll 40 patients at the RPTD level within 2 years in order to provide a preliminary estimate of progression-free survival (primary endpoint of the trial) in the target population.

Conditions

Cholangiocarcinoma; Biliary Tract Cancer; Gallbladder Cancer

Keywords

Cholangiocarcinoma; Biliary Tract Cancer; Gallbladder Cancer

Outcome Measures

Primary Outcomes (2)

• Phase I: Recommended Phase II Dose (RPTD) of the Combination of Sorafenib and GEMOX in Patients With Advanced Biliary Tract Cancer (BTC).

  Establish the recommended phase II dose (RPTD) of the combination of sorafenib and GEMOX in patients with advanced biliary tract cancer (BTC).

  First two 14-day Phase I cycles

• Phase II: Obtain an Estimate of the 9-month Progression-free Survival Rate in Patients With Advanced BTC Receiving the RPTD of the Combination Sorafenib and GEMOX.

  Rate of study participants achieving progression-free survival at 9 months post-initiation of study therapy at RPTD. Progression-Free Survival (PFS) is defined as the time elapsed from the start of treatment to the date of documented progression or death, whichever comes first. For surviving patients without progression who begin alternative treatment, PFS will be censored at the last date of documented progression-free status prior to starting alternative treatment. Similarly, losses to follow up will be censored at the last date of documented progression-free status.

  9 Months

Secondary Outcomes (4)

• Phase II: Estimate Overall Response Rate and Clinical Benefit Rate.

  About 9 Months

• Phase II: Estimate Overall Survival

  Start of treatment until death or date of last contact

• Phase II: Further Evaluate the Safety of the Proposed Combination

  About 9 Months

• Phase II: Explore Biomarkers of Response to the Combination

  Baseline, Day 1 of Cycle 2 and subsequent cycles, about 9 Months

Study Arms (2)

Phase 1: GEMOX + Sorafenib

EXPERIMENTAL

Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib. * Gemcitabine: 1000 or 750 mg/m2, IV, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops. * Oxaliplatin: 100 or 75 mg/m2, IV, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops. * Sorafenib: 200 mg, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.

Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Sorafenib

Phase 2 - RPTD GEMOX + Sorafenib

EXPERIMENTAL

Recommended Phase Two Dose (RPTD) of Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib: * Gemcitabine: Recommended Phase II Dose determined from Phase I, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops. * Oxaliplatin: Recommended Phase II Dose determined from Phase I, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops. * Sorafenib: Recommended Phase II Dose determined from Phase I, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.

Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Sorafenib

Interventions

Gemcitabine DRUG

Intravenously (IV) on Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.

Also known as: Gemzar

Phase 1: GEMOX + Sorafenib; Phase 2 - RPTD GEMOX + Sorafenib

Oxaliplatin DRUG

Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.

Also known as: Eloxatin

Phase 1: GEMOX + Sorafenib; Phase 2 - RPTD GEMOX + Sorafenib

Sorafenib DRUG

Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.

Also known as: BAY 43-9006

Phase 1: GEMOX + Sorafenib; Phase 2 - RPTD GEMOX + Sorafenib

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• Histologically or cytologically confirmed biliary tract or gallbladder carcinoma
• Any stage of disease is allowed but the patients must not be candidates for curative resection
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 in Ph I
• ECOG performance status 0-2 in Ph II. Patients with ECOG PS of 2 will only be enrolled if they will comprise at most 25% of the total accruals. This will be monitored in real time to ensure that at any point during accrual, PS 2 patients will comprise \<= 25% of the total accruals
• Patients must have normal organ and marrow function as defined below within 14 days of study entry:
• Absolute neutrophil count \>= 1,500 cells/mm3
• Platelet count \>= 60,000/mm3
• Creatinine \< 1.5 upper limit of normal (ULN).
• Aspartate transaminase (AST) and Alanine transaminase (ALT) \<= 2.5 x ULN.
• Bilirubin \<= 3.0 mg/dl
• International normalized ratio (INR) \< 1.5 or a prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin will not be candidates for the trial. Patients on anticoagulation with low molecular weight or heparinoids are protocol candidates.
• Any number of previous lines of chemotherapy is allowed for the phase I portion
• During the phase II trial, no prior chemotherapy for inoperable or metastatic disease is allowed except 5-FU or Capecitabine as radiosensitizers. Prior adjuvant chemotherapy is allowed.
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment

You may not qualify if:

• Investigational agents within 28 days prior to Day 1 of study
• Chemotherapy within 4 weeks prior to Day 1 of study
• Nitrosoureas, mitomycin-C within 6 weeks prior to Day 1 of study.
• Prior treatment with sorafenib, gemcitabine or oxaliplatin
• Prior history of peripheral neuropathy \> Grade 1 (e.g., diabetic neuropathy)
• Pregnant or breast-feeding female
• Patients with a history of allergic reactions or sensitivity attributed to compounds of similar chemical or biologic composition to sorafenib, oxaliplatin or gemcitabine
• Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)
• Cardiac disease: Congestive heart failure \> class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management.
• Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
• Known human immunodeficiency virus (HIV) infection and Hepatitis B and Hepatitis C.
• Active clinically serious infection \> CTCAE Grade 2.
• Arterial thrombotic/embolic events like myocardial infarct and cerebrovascular accident including transient ischemic attacks within the past 6 months.

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Cholangiocarcinoma; Biliary Tract Neoplasms; Gallbladder Neoplasms

Interventions

Gemcitabine; Oxaliplatin; Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Limitations and Caveats

Study terminated due to lack of funding prior to the opening of the Phase 2 arm. Minimum required enrollment of 18 evaluable participants for Phase 1 not met.

Results Point of Contact

• Title: Peter J. Hosein MD
• Organization: University of Miami

phosein@miami.edu

3052433462

Study Officials

• Peter Hosein, MD

  University of Miami

  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: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Clinical

Study Record Dates

• First Submitted: August 6, 2009
• First Posted: August 10, 2009
• Study Start: August 1, 2009
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: January 3, 2018
• Results First Posted: February 13, 2015

Record last verified: 2017-12

Locations

US (1)