Gemcitabine Plus Pemetrexed Disodium in Treating Patients With Unresectable or Metastatic Biliary Tract or Gallbladder Cancer

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT00059865

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Duration (Months)

1.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy such as gemcitabine work in different ways to stop tumor cells from dividing so they stop growing or die. Pemetrexed disodium may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining gemcitabine with pemetrexed disodium may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of gemcitabine when given together with pemetrexed disodium to see how well it works in treating patients with unresectable or metastatic biliary tract or gallbladder cancer.

Condition or Disease	Intervention/Treatment	Phase
Extrahepatic Bile Duct Cancer Gallbladder Cancer Liver Cancer	Drug: gemcitabine hydrochloride Drug: pemetrexed disodium	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose of gemcitabine when administered with pemetrexed disodium in patients with unresectable or metastatic biliary tract or gallbladder cancer. (Phase I closed to accrual as of Oct. 2005.)
Determine the 6-month survival rate of patients treated with this regimen.
Determine the best objective tumor response rate and duration of best objective tumor response in patients treated with this regimen.
Determine the time to progression and overall survival of patients treated with this regimen.
Determine the toxic effects of this regimen in these patients.
Determine the individual patient variation in toxicity of and/or response to this regimen due to genetic differences in proteins involved in drug response in these patients.

OUTLINE: This is a multicenter phase I dose-escalation study of gemcitabine followed by a phase II study.

Phase I: Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity (phase I closed to accrual as of October 2005).

Cohorts of 3-6 patients receive escalating doses of gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive pemetrexed disodium as in phase I and gemcitabine at the recommended phase II dose.

Patients are followed every 3 months for 1 year and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 85 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

68 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I/II Trial Of Gemcitabine And ALIMTA In Patients With Measurable Or Evaluable, Unresectable Or Metastatic Biliary Tract Carcinoma (Intrahepatic, Extrahepatic, Ampulla Or Vater) And Gallbladder Carcinoma

Study Start Date :

Jan 1, 2004

Actual Primary Completion Date :

Feb 1, 2007

Actual Study Completion Date :

Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: pemetrexed + gemcitabine Phase II: Patients receive pemetrexed disodium as in phase I and gemcitabine at the recommended phase II dose. Patients are followed every 3 months for 1 year and then every 6 months for 4 years.	Drug: gemcitabine hydrochloride Drug: pemetrexed disodium

Arm

Intervention/Treatment

Experimental: pemetrexed + gemcitabine

Phase II: Patients receive pemetrexed disodium as in phase I and gemcitabine at the recommended phase II dose. Patients are followed every 3 months for 1 year and then every 6 months for 4 years.

Drug: gemcitabine hydrochloride

Drug: pemetrexed disodium

Outcome Measures

Primary Outcome Measures

Survival after 6 months of treatment [Up to 6 months]

Secondary Outcome Measures

Response as assessed by RECIST criteria every 8-16 weeks [Up to 16 weeks]
Toxicity as assessed by CTC v3 every 4 weeks [Up to 4 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

One of the following histologically or cytologically confirmed cancers not amenable to treatment with combined chemotherapy and radiotherapy:
Biliary tract (intrahepatic, extrahepatic, or ampulla of Vater) carcinoma
Gallbladder carcinoma
Unresectable or metastatic disease
No CNS metastases
Prior brain metastases treated with surgery or radiosurgery allowed provided treatment was completed at least 4 weeks ago and there is no evidence of CNS progression
No clinically significant pericardial or pleural effusion or ascites unless able to be drained before study entry
Performance status - ECOG 0-2
At least 3 months
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Bilirubin no greater than 3 times upper limit of normal (ULN)
AST no greater than 5 times ULN
Creatinine no greater than 1.5 times ULN
Creatinine clearance at least 45 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer
Able to tolerate folic acid, corticosteroids, or cyanocobalamin supplements
More than 4 weeks since prior biologic or immunologic therapy
No prior biologic or immunologic therapy for metastatic disease
No concurrent immunotherapy
No concurrent colony-stimulating factors during course 1
No prior chemotherapy for metastatic disease
No prior gemcitabine
Prior chemoembolization allowed provided the following are true:
At least 4 weeks since prior chemoembolization
Evidence of new tumor growth since therapy
At least 6 months since prior chemotherapy used as a radiosensitizer (in adjuvant setting or for locally advanced disease)
No other concurrent chemotherapy
Prior radiofrequency ablation allowed provided the following are true:
At least 4 weeks since prior radiofrequency ablation
Evidence of new tumor growth since therapy
No prior radiotherapy to 25% or more of the bone marrow
More than 4 weeks since prior radiotherapy
No concurrent radiotherapy
Prior embolization allowed provided the following are true:
At least 4 weeks since prior embolization
Evidence of new tumor growth since therapy
No prior pemetrexed disodium
No aspirin or nonsteroidal anti-inflammatory drugs for at least 2 days (5 days for long-acting agents [e.g., piroxicam]) before, during, and for at least 2 days after administration of pemetrexed disodium
No concurrent cyclo-oxygenase-2 inhibitors

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
2	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
3	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
4	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
5	Southwest Medical Center	Liberal	Kansas	United States	67901
6	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
7	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
8	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
9	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
10	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
11	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67203
12	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
13	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
14	CCOP - Wichita	Wichita	Kansas	United States	67214
15	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
16	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
17	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
18	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
19	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
20	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
21	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
22	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
23	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
24	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
25	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
26	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
27	Park Nicollet Cancer Center	St. Louis Park	Minnesota	United States	55416
28	United Hospital	St. Paul	Minnesota	United States	55102
29	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
30	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
31	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
32	AnMed Cancer Center	Anderson	South Carolina	United States	29621
33	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
34	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
35	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
36	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
37	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
38	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
39	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
40	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
41	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235