Clinical trial NCT00059865: Gemcitabine Plus Pemetrexed Disodium in Treating Patients With Unresectable or Metastatic Biliary Tract or Gallbladder Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Extrahepatic Bile Duct Cancer
Gallbladder Cancer
Liver Cancer
Keywords: advanced adult primary liver cancer
unresectable gallbladder cancer
unresectable extrahepatic bile duct cancer
adult primary cholangiocellular carcinoma
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-05-07
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: * 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

Primary outcomes:
measure: Survival after 6 months of treatment
timeFrame: Up to 6 months
Secondary outcomes:
measure: Response as assessed by RECIST criteria every 8-16 weeks
timeFrame: Up to 16 weeks
measure: Toxicity as assessed by CTC v3 every 4 weeks
timeFrame: Up to 4 weeks
Other outcomes:
Locations:
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Escanaba
country: United States
facility: Green Bay Oncology, Limited - Escanaba
state: Michigan
city: Iron Mountain
country: United States
facility: Dickinson County Healthcare System
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology, PA - Maplewood
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Robbinsdale
country: United States
facility: Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: St. Louis Park
country: United States
facility: Park Nicollet Cancer Center
state: Minnesota
city: St. Paul
country: United States
facility: United Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology Hematology, PA - Woodbury
state: Minnesota
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Anderson
country: United States
facility: AnMed Cancer Center
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: St. Mary's Hospital Medical Center - Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Cancer Care Center at Bay Area Medical Center
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology, Limited - Oconto Falls
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology, Limited - Sturgeon Bay
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Steven R. Alberts, MD
role: STUDY_CHAIR
References:
citation: Alberts SR, Foster NR, McWilliams RR, et al.: NCCTG phase I/II trial (N9943) of gemcitabine and pemetrexed in patients with unresectable or metastatic biliary tract carcinoma and gallbladder carcinoma: interim results. [Abstract] American Society of Clinical Oncology 2007 Gastrointestinal Cancers Symposium, 19 -21 January 2007, Orlando, Florida A-149, 2007.
citation: Alberts SR, Sande JR, Foster NR, Quevedo FJ, McWilliams RR, Kugler JW, Fitch TR, Jaslowski AJ. Pemetrexed and gemcitabine for biliary tract and gallbladder carcinomas: a North Central Cancer Treatment Group (NCCTG) phase I and II Trial, N9943. J Gastrointest Cancer. 2007;38(2-4):87-94. doi: 10.1007/s12029-008-9037-8. Epub 2008 Nov 21.
citation: McWilliams RR, Foster NR, Quevedo FJ, et al.: NCCTG phase I/II trial (N9943) of gemcitabine and pemetrexed in patients with biliary tract or gallbladder carcinoma: phase II results. [Abstract] J Clin Oncol 25 (Suppl 18): A-4578, 2007.