Gemcitabine, Oxaliplatin, Tarceva &/or Cisplatin in HCC & Biliary Tree Cancers

NCT ID: NCT00832637

Last Updated: 2018-06-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2017-03-15

Brief Summary

This is a single arm phase II trial of Gemcitabine and Oxaliplatin (Gem-Ox) with Erlotinib (Tarceva) for the treatment of hepatocellular carcinoma (HCC) and biliary tree cancer (BTC) patients with platelet counts 100,000/µL. The purpose of this study is to determine the tumor control rate following treatment with GEM-OX combined with Tarceva in patients with HCC. Tumor control rate is defined as the percentage of patients achieving a complete response, partial response, or stable disease at 24 weeks following treatment.

Detailed Description

The incidence and mortality of HCC has increased in the United States. Promising responses have been observed in HCC patients treated with gemcitabine and cisplatin, inclusing good disease stabilization and progression free survival. Cisplatin-gemcitabine enhances the cytotoxicity of cisplatin by increasing the formation of cytotoxic platinum DNA adducts. Similarly, Oxaliplatin also has DNA cross linkage properties and one could assume that its combination with gemcitabine is likely to potentiate the cytotoxicity of the latter. Erlotinib has also been reported to result in clinical benefit in HCC and BTC patients. Based on these prior findings, we embarked on this phase II protocol of gemcitabine, oxaliplatin, and erlotinib in HCC and BTC patients.

Conditions

Hepatocellular Carcinoma; Cholangiocellular Carcinoma; Cholangiocarcinoma of the Extrahepatic Bile Duct; Bile Duct Cancer; Periampullary Adenocarcinoma; Gallbladder Cancer; Extrahepatic Bile Duct Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gemcitabine, Cisplatin, Erlotinib

A combination of Cisplatin at 40 mg/m2 + Gemcitabine at 1000 mg/m2, every 28 days + Erlotinib 100 mg daily, orally. Cycles will be repeated every four weeks.

Group Type: EXPERIMENTAL

Cisplatin

Intervention Type: DRUG

Cisplatin is administered intravenously at 40 mg/m2 on day 1 and day 15, every 28 days. Cisplatin is administered following Gemcitabine. Cisplatin administration should occur with hydration with normal saline at 250 mL/ hour for at least 4 hours before and during Cisplatin administration. Additionally, Cisplatin administration should be preceded by osmotic diuresis with Mannitol 25%, 12.5 grams.

Erlotinib

Intervention Type: DRUG

100 mg orally daily. For grade 3 or 4 skin rash, erlotinib should be held until resolution of the rash to no more than grade 1 before resumption of erlotinib.

Gemcitabine

Intervention Type: DRUG

Gemcitabine is administered intravenously at 1000 mg/m2 on day 1 and 15, every 28 days. The clinical formulation is supplied in a sterile form for intravenous use only. Vials of gemcitabine contain either 200 mg or 1 g of gemcitabine hydrochloride (HCl )(expressed as free base) formulated with mannitol (200 mg or 1 g, respectively) and sodium acetate (12.5 mg or 62.5 mg, respectively) as a sterile lyophilized powder. Hydrochloric acid and/or sodium hydroxide may have been added for pH adjustment.

Interventions

Cisplatin

Cisplatin is administered intravenously at 40 mg/m2 on day 1 and day 15, every 28 days. Cisplatin is administered following Gemcitabine. Cisplatin administration should occur with hydration with normal saline at 250 mL/ hour for at least 4 hours before and during Cisplatin administration. Additionally, Cisplatin administration should be preceded by osmotic diuresis with Mannitol 25%, 12.5 grams.

Intervention Type: DRUG

Erlotinib

100 mg orally daily. For grade 3 or 4 skin rash, erlotinib should be held until resolution of the rash to no more than grade 1 before resumption of erlotinib.

Intervention Type: DRUG

Gemcitabine

Gemcitabine is administered intravenously at 1000 mg/m2 on day 1 and 15, every 28 days. The clinical formulation is supplied in a sterile form for intravenous use only. Vials of gemcitabine contain either 200 mg or 1 g of gemcitabine hydrochloride (HCl )(expressed as free base) formulated with mannitol (200 mg or 1 g, respectively) and sodium acetate (12.5 mg or 62.5 mg, respectively) as a sterile lyophilized powder. Hydrochloric acid and/or sodium hydroxide may have been added for pH adjustment.

Intervention Type: DRUG

Other Intervention Names

Platinol®; Tarceva®; Gemzar®

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed hepatocellular carcinoma (HCC) or biliary tree cancer (BTC:: intra- and extra-hepatic cholanciocarcinoma, bile duct cancer, adenocarcinoma of the Ampulla of Vater and/or gallbladder carcinoma).
• Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST).
• Age 18 years or older.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2
• Adequate bone marrow as evidenced by:

• Absolute neutrophil count (ANC) > 1,500/L.
• Platelet count > 100,000/L.
• Absence of a regular red blood cell transfusion requirement.
• Adequate renal function as evidenced by serum creatinine < 1.5 mg/dL.
• Adequate hepatic function as evidenced by:

• Serum total bilirubin 1.5x Upper Limit of Normal (ULN).
• Alkaline phosphatase < 3x ULN for the reference lab (< 5x ULN for patients with known hepatic metastases).
• Serum glutamic-oxaloacetic transaminase (SGOT)/ serum glutamic-pyruvic transaminase (SGPT) < 3x ULN for the reference lab (< 5x ULN for patients with known hepatic metastases).
• Patients must have a life expectancy of 12 weeks.
• Patients must be recovered from both acute and late effects of any prior surgery, radiotherapy or other antineoplastic therapy.
• Patients of childbearing potential agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication (an effective form of contraception is an oral contraceptive or a double barrier method).

Exclusion Criteria

A patient may not be enrolled in the trial if any of the following criteria are met:

• Patients with an active infection or with a fever > 38.50 degrees Celcius within 3 days of the first scheduled day of protocol treatment.
• Patients with active central nervous system (CNS) metastases. Patients with stable CNS disease, who have undergone radiotherapy at least 4 weeks prior to the planned first protocol treatment and who have been on a stable dose of corticosteroids for 3 weeks are eligible for the trial.
• History of prior malignancy within the past 5 years except for curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current prostate serum antigen (PSA) of < 1.0 mg/dL on 2 successive evaluations at least 3 months apart, with the most recent evaluation within 4 weeks of entry.
• Patients with prior treatment or known hypersensitivity to any of the components of oxaliplatin or gemcitabine.
• Patients who have received chemotherapy within 30 days of the first scheduled day of protocol treatment.
• Patients who received radiotherapy to more than 25% of their bone marrow; or patients who received any radiotherapy within 4 weeks of entry.
• Patients who are receiving concurrent investigational therapy or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication).
• Peripheral neuropathy Grade 2.
• Patients who are pregnant or lactating.
• Patients with a life expectancy of less than 12 weeks.
• Any other medical condition, including mental illness or substance abuse, deemed by the Investigator, likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
• Patients with any of the following laboratory parameters:

• Abnormal hematological values with ANC < 1500/mm3, thrombocytopenia < 99,000.
• Impaired renal function with a serum creatinine > 1.5x ULN.
• Serum bilirubin > 1.5xULN.
• Albumin < 2.5 mg/dl.
• Unwillingness to participate or inability to comply with the protocol for the duration of the study.
• History of allogeneic transplant.
• Known human immunodeficiency virus (HIV).
• Clinically significant heart disease defined as New York Heart Association (NYHA) class 3 or 4 heart disease.
• Known or existing uncontrolled coagulopathy.
• Patients with severe medical problems such as uncontrolled diabetes or chronically debilitating diseases that the investigator feels might compromise the study participant.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

New Mexico Cancer Research Alliance

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yehuda Patt, MD

Role: PRINCIPAL_INVESTIGATOR

University of New Mexico

Ari D Baron, MD

Role: PRINCIPAL_INVESTIGATOR

California Pacific Medical Center

Locations

California Pacific Medical Center

San Francisco, California, United States

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Countries

United States

Related Links

http://www.cancer.unm.edu

University of New Mexico Cancer Center

http://www.nmcca.org

New Mexico Cancer Care Alliance

Other Identifiers

NCI-2011-02729

Identifier Type: REGISTRY

Identifier Source: secondary_id

B9E-US-X467

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

INST OX-05-024

Identifier Type: -

Identifier Source: org_study_id