Gem-ox: Gemcitabine, Oxaliplatin, Tarceva &/or Cisplatin in HCC & Biliary Tree Cancers

• Sponsor: New Mexico Cancer Care Alliance (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00832637
• Collaborator: (none)
• Enrollment: 33
• Locations: 2
• Arm: 1
• Duration (Months): 115.4
• Patients Per Site: 16.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma; Cholangiocellular Carcinoma; Cholangiocarcinoma of the Extrahepatic Bile Duct; Bile Duct Cancer; Periampullary Adenocarcinoma; Gallbladder Cancer; Extrahepatic Bile Duct Cancer	Drug: Cisplatin; Drug: Erlotinib; Drug: Gemcitabine	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Gemcitabine and Cisplatin With Erlotinib in Hepatocellular Carcinoma (HCC) and Biliary Tree Cancer (BTC) (Intra- and Extra-hepatic Cholangiocarcinoma, Bile Duct Cancer, Adenocarcinoma of the Ampulla of Vater and Gallbladder Carcinoma)
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Mar 15, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Drug: 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.; Other Names: Platinol® ; 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.; Other Names: Tarceva® ; 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.; Other Names: Gemzar®

Outcome Measures

Primary Outcome Measures

1. Tumor Control Rate [24 weeks]

   Rate of tumor control is defined as the percentage of patients achieving a complete response (CR) + partial response (PR) + stable disease (SD) at 24 weeks following treatment. Response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures

1. Overall Response Rate [24 weeks]

   Overall response rate is defined as the percentage of patients achieving a complete response (CR) + partial response (PR) at 24 weeks following treatment. Response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

2. Time to Tumor Progression (TTP) [2 years]

   The time from treatment initiation to disease progression. Progression is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI): Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

3. Median Survival Time (MST) [2 years]

   Survival is defined as the time from treatment initiation to death by any cause

4. Toxicity [Patients are followed for at least one month following end of on-study treatment. All patients who discontinue the trial secondary to an adverse event are followed until resolution, stabilization or return to a baseline condition. An average of 24 weeks]

   Toxicity will be evaluated per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Frequency and severity of adverse events will be tabulated using counts of frequently occurring, serious and severe events of interest (i.e. Grade 3 and Grade 4 adverse events).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Pacific Medical Center	San Francisco	California	United States	94115
2	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131

Sponsors and Collaborators

• New Mexico Cancer Care Alliance

Investigators

• Principal Investigator: Yehuda Patt, MD, University of New Mexico
• Principal Investigator: Ari D Baron, MD, California Pacific Medical Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of New Mexico Cancer Center
• New Mexico Cancer Care Alliance

Publications

None provided.

• Responsible Party: New Mexico Cancer Care Alliance
• ClinicalTrials.gov Identifier: NCT00832637
• Other Study ID Numbers: INST OX-05-024; NCI-2011-02729; B9E-US-X467
• First Posted: Jan 30, 2009
• Last Update Posted: Jun 29, 2018
• Last Verified: Jun 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by New Mexico Cancer Care Alliance: Liver; Gallbladder; Bile duct; Gemzar; Eloxatin; Tarceva; erlotinib; Gem-ox
• Additional relevant MeSH terms: Carcinoma; Adenocarcinoma; Carcinoma, Hepatocellular; Cholangiocarcinoma; Gallbladder Neoplasms; Bile Duct Neoplasms; Gemcitabine; Erlotinib Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Gemcitabine, Cisplatin, Erlotinib
Arm/Group Description	Cisplatin at a dose of 40 mg/m2 q 2 weeks along with gemcitabine, 1000mg/m2, and erlotinib 100 mg daily PO. Cisplatin: Cisplatin 40 mg/ m2 on day 1 and day 15 in patients treated with Gem + Cis, with Cisplatin to be given following Gemcitabine. Cisplatin administration should be given along with hydration with NS at 250 mL/ hour for at least 4 hours pre-and during Cisplatin administration. Additionally, Cisplatin administration should be preceded by osmotic diuresis with Mannitol 25%, 12.5 grams. Erlotinib: 100 mg orally daily. Gemcitabine: 1000 mg/m2 on Days 1, 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 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.
Period Title: Overall Study
STARTED	33
COMPLETED	33
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Gemcitabine, Cisplatin, Erlotinib
Arm/Group Description	Cisplatin at a dose of 40 mg/m2 q 2 weeks along with gemcitabine, 1000mg/m2, and erlotinib 100 mg daily PO. Cisplatin: Cisplatin 40 mg/ m2 on day 1 and day 15 in patients treated with Gem + Cis, with Cisplatin to be given following Gemcitabine. Cisplatin administration should be given along with hydration with NS at 250 mL/ hour for at least 4 hours pre-and during Cisplatin administration. Additionally, Cisplatin administration should be preceded by osmotic diuresis with Mannitol 25%, 12.5 grams. Erlotinib: 100 mg orally daily. Gemcitabine: 1000 mg/m2 on Days 1, 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 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.
Overall Participants	33
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59
Sex: Female, Male (Count of Participants)
Female	8 24.2%
Male	25 75.8%

Outcome Measures

1. Primary Outcome

Title	Tumor Control Rate
Description	Rate of tumor control is defined as the percentage of patients achieving a complete response (CR) + partial response (PR) + stable disease (SD) at 24 weeks following treatment. Response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine, Cisplatin, Erlotinib
Arm/Group Description	Cisplatin at a dose of 40 mg/m2 q 2 weeks along with gemcitabine, 1000mg/m2, and erlotinib 100 mg daily PO. Cisplatin: Cisplatin 40 mg/ m2 on day 1 and day 15 in patients treated with Gem + Cis, with Cisplatin to be given following Gemcitabine. Cisplatin administration should be given along with hydration with NS at 250 mL/ hour for at least 4 hours pre-and during Cisplatin administration. Additionally, Cisplatin administration should be preceded by osmotic diuresis with Mannitol 25%, 12.5 grams. Erlotinib: 100 mg orally daily. Gemcitabine: 1000 mg/m2 on Days 1, 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 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.
Measure Participants	33
Complete response (CR)	0 0%
Partial response (PR)	7.1 21.5%
Stable disease (SD)	53.6 162.4%
CR + PR + SD	60.7 183.9%

2. Secondary Outcome

Title	Overall Response Rate
Description	Overall response rate is defined as the percentage of patients achieving a complete response (CR) + partial response (PR) at 24 weeks following treatment. Response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine, Cisplatin, Erlotinib
Arm/Group Description	Cisplatin at a dose of 40 mg/m2 q 2 weeks along with gemcitabine, 1000mg/m2, and erlotinib 100 mg daily PO. Cisplatin: Cisplatin 40 mg/ m2 on day 1 and day 15 in patients treated with Gem + Cis, with Cisplatin to be given following Gemcitabine. Cisplatin administration should be given along with hydration with NS at 250 mL/ hour for at least 4 hours pre-and during Cisplatin administration. Additionally, Cisplatin administration should be preceded by osmotic diuresis with Mannitol 25%, 12.5 grams. Erlotinib: 100 mg orally daily. Gemcitabine: 1000 mg/m2 on Days 1, 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 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.
Measure Participants	28
Complete response (CR)	0 0%
Partial response (PR)	7.1 21.5%
CR + PR	7.1 21.5%

3. Secondary Outcome

Title	Time to Tumor Progression (TTP)
Description	The time from treatment initiation to disease progression. Progression is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI): Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine, Cisplatin, Erlotinib
Arm/Group Description	Cisplatin at a dose of 40 mg/m2 q 2 weeks along with gemcitabine, 1000mg/m2, and erlotinib 100 mg daily PO. Cisplatin: Cisplatin 40 mg/ m2 on day 1 and day 15 in patients treated with Gem + Cis, with Cisplatin to be given following Gemcitabine. Cisplatin administration should be given along with hydration with NS at 250 mL/ hour for at least 4 hours pre-and during Cisplatin administration. Additionally, Cisplatin administration should be preceded by osmotic diuresis with Mannitol 25%, 12.5 grams. Erlotinib: 100 mg orally daily. Gemcitabine: 1000 mg/m2 on Days 1, 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 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.
Measure Participants	33
Median (95% Confidence Interval) [weeks]	22

4. Secondary Outcome

Title	Median Survival Time (MST)
Description	Survival is defined as the time from treatment initiation to death by any cause
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine, Cisplatin, Erlotinib
Arm/Group Description	Cisplatin at a dose of 40 mg/m2 q 2 weeks along with gemcitabine, 1000mg/m2, and erlotinib 100 mg daily PO. Cisplatin: Cisplatin 40 mg/ m2 on day 1 and day 15 in patients treated with Gem + Cis, with Cisplatin to be given following Gemcitabine. Cisplatin administration should be given along with hydration with NS at 250 mL/ hour for at least 4 hours pre-and during Cisplatin administration. Additionally, Cisplatin administration should be preceded by osmotic diuresis with Mannitol 25%, 12.5 grams. Erlotinib: 100 mg orally daily. Gemcitabine: 1000 mg/m2 on Days 1, 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 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.
Measure Participants	33
Median (95% Confidence Interval) [weeks]	28

5. Secondary Outcome

Title	Toxicity
Description	Toxicity will be evaluated per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Frequency and severity of adverse events will be tabulated using counts of frequently occurring, serious and severe events of interest (i.e. Grade 3 and Grade 4 adverse events).
Time Frame	Patients are followed for at least one month following end of on-study treatment. All patients who discontinue the trial secondary to an adverse event are followed until resolution, stabilization or return to a baseline condition. An average of 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine, Cisplatin, Erlotinib
Arm/Group Description	Cisplatin at a dose of 40 mg/m2 q 2 weeks along with gemcitabine, 1000mg/m2, and erlotinib 100 mg daily PO. Cisplatin: Cisplatin 40 mg/ m2 on day 1 and day 15 in patients treated with Gem + Cis, with Cisplatin to be given following Gemcitabine. Cisplatin administration should be given along with hydration with NS at 250 mL/ hour for at least 4 hours pre-and during Cisplatin administration. Additionally, Cisplatin administration should be preceded by osmotic diuresis with Mannitol 25%, 12.5 grams. Erlotinib: 100 mg orally daily. Gemcitabine: 1000 mg/m2 on Days 1, 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 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.
Measure Participants	33
Anemia	2 6.1%
Neutropenia	7 21.2%
Neutropenic Fever	2 6.1%
Thrombocytopenia	6 18.2%
Diarrhea	4 12.1%
Abdominal Pain	2 6.1%
Renal Failure	1 3%
Dermatitis (acneiform)	3 9.1%
Peripheral neuropathy	1 3%
Metabolic syndrome	2 6.1%
Cerebral hemorrhage	1 3%

Adverse Events

Time Frame	Patients are followed for at least one month following end of on-study treatment. All patients who discontinue the trial secondary to an adverse event are followed until resolution, stabilization or return to a baseline condition, an average of 24 weeks.
Arm/Group Title	Gemcitabine, Cisplatin, Erlotinib
Arm/Group Description	Cisplatin at a dose of 40 mg/m2 q 2 weeks along with gemcitabine, 1000mg/m2, and erlotinib 100 mg daily PO. Cisplatin: Cisplatin 40 mg/ m2 on day 1 and day 15 in patients treated with Gem + Cis, with Cisplatin to be given following Gemcitabine. Cisplatin administration should be given along with hydration with NS at 250 mL/ hour for at least 4 hours pre-and during Cisplatin administration. Additionally, Cisplatin administration should be preceded by osmotic diuresis with Mannitol 25%, 12.5 grams. Erlotinib: 100 mg orally daily. Gemcitabine: 1000 mg/m2 on Days 1, 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 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.
All Cause Mortality
	Gemcitabine, Cisplatin, Erlotinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemcitabine, Cisplatin, Erlotinib
	Affected / at Risk (%)	# Events
Total	17/33 (51.5%)
Blood and lymphatic system disorders
Hemolysis (Red blood cell destruction)	1/33 (3%)	1
Gastrointestinal disorders
Anorexia (Loss of appetite)	1/33 (3%)	1
Ascites	2/33 (6.1%)	2
Diarrhea	1/33 (3%)	1
Gastritis (Stomach lining inflammation)	1/33 (3%)	1
Upper gastrointestinal hemorrhage	1/33 (3%)	1
General disorders
Fatigue	1/33 (3%)	1
Fever	2/33 (6.1%)	3
Abdominal pain	2/33 (6.1%)	2
Chest pain	1/33 (3%)	1
Death	4/33 (12.1%)	4
Immune system disorders
Hypersensitivity reaction	1/33 (3%)	1
Infections and infestations
Device related infection	1/33 (3%)	1
Febrile neutropenia	1/33 (3%)	1
Pneumonia	2/33 (6.1%)	2
Urinary tract infection	1/33 (3%)	1
Investigations
Hypokalemia (Low potassium level in blood)	1/33 (3%)	1
Nervous system disorders
Extrapyramidal disorder	1/33 (3%)	1
Renal and urinary disorders
Renal failure	1/33 (3%)	1
Other (Not Including Serious) Adverse Events
	Gemcitabine, Cisplatin, Erlotinib
	Affected / at Risk (%)	# Events
Total	32/33 (97%)
Blood and lymphatic system disorders
Hemoglobin decreased	5/33 (15.2%)	12
Hemolysis (Red blood cell destruction)	7/33 (21.2%)	7
Leukocytes decreased	7/33 (21.2%)	10
Neutrophils decreased	7/33 (21.2%)	18
Platelet count decreased	14/33 (42.4%)	44
Cardiac disorders
Atrial tachycardia	2/33 (6.1%)	2
Gastrointestinal disorders
Abdominal distention	3/33 (9.1%)	3
Anorexia (Loss of appetite)	10/33 (30.3%)	10
Ascites (Accumulation of fluid in the abdomen)	4/33 (12.1%)	4
Constipation	8/33 (24.2%)	9
Dehydration	6/33 (18.2%)	7
Diarrhea	18/33 (54.5%)	22
Gastritis (Stomach lining inflammation)	2/33 (6.1%)	2
Nausea	16/33 (48.5%)	19
Vomiting	11/33 (33.3%)	14
General disorders
Rhinitis (Runny nose)	5/33 (15.2%)	12
Fatigue	22/33 (66.7%)	27
Fever	8/33 (24.2%)	9
Weight Loss	5/33 (15.2%)	6
Epistaxis (Nosebleed)	3/33 (9.1%)	3
Edema: limbs	3/33 (9.1%)	5
Edema: trunk/genital	2/33 (6.1%)	3
Abdominal pain	5/33 (15.2%)	8
Extremity - Limb pain	2/33 (6.1%)	2
Neck Pain	2/33 (6.1%)	2
Infections and infestations
Febrile neutropenia	3/33 (9.1%)	3
Urinary Tract Infection	2/33 (6.1%)	2
Investigations
Alkaline phosphatase increased	2/33 (6.1%)	3
Aspartate aminotransferase increased	2/33 (6.1%)	2
Hyperbilirubinemia (High level of bilirubin)	6/33 (18.2%)	10
Hyperglycemia (High glucose level in blood)	3/33 (9.1%)	4
Hypoalbuminemia (Low level of albumin in blood)	4/33 (12.1%)	8
Hypocalcemia (Low calcium level in blood)	3/33 (9.1%)	5
ypocalcemia (Low calcium level in blood)	3/33 (9.1%)	5
Hypokalemia (Low potassium level in blood)	5/33 (15.2%)	9
Hypomagnesemia (Low magnesium level in blood)	3/33 (9.1%)	4
Hyponatremia (Low sodium level in blood)	4/33 (12.1%)	5
Nervous system disorders
Anxiety	3/33 (9.1%)	3
Confusion	4/33 (12.1%)	4
Dizziness	2/33 (6.1%)	2
Headache	2/33 (6.1%)	4
Insomnia	7/33 (21.2%)	7
Peripheral motor neuropathy	3/33 (9.1%)	3
Peripheral sensory neuropathy	3/33 (9.1%)	5
Respiratory, thoracic and mediastinal disorders
Cough	2/33 (6.1%)	2
Dyspnea (Shortness of breath)	2/33 (6.1%)	2
Hiccups	3/33 (9.1%)	3
Skin and subcutaneous tissue disorders
Alopecia (Hair loss)	2/33 (6.1%)	3
Hand and foot syndrome	2/33 (6.1%)	3
Rash	6/33 (18.2%)	7
Acne	9/33 (27.3%)	12
Desquamating rash	9/33 (27.3%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.