Clinical trial NCT00019513: Combination Chemotherapy in Treating Patients With Recurrent, Refractory, or Metastatic Solid Tumors or Lymphomas
Official title: A Phase I Study of Weekly Gemcitabine in Combination With Infusional 5-Fluorouracil and Oral Calcium Leucovorin in Adult Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Cancer
Esophageal Cancer
Extrahepatic Bile Duct Cancer
Gallbladder Cancer
Liver Cancer
Lung Cancer
Lymphoma
Pancreatic Cancer
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: stage IV adult Hodgkin lymphoma
recurrent adult Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
small intestine lymphoma
unspecified adult solid tumor, protocol specific
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
anaplastic large cell lymphoma
stage IV mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome
recurrent adult primary liver cancer
advanced adult primary liver cancer
adult primary cholangiocellular carcinoma
stage IV non-small cell lung cancer
recurrent non-small cell lung cancer
extensive stage small cell lung cancer
recurrent small cell lung cancer
recurrent pancreatic cancer
stage IV esophageal cancer
recurrent esophageal cancer
recurrent colon cancer
stage IV colon cancer
recurrent gallbladder cancer
unresectable gallbladder cancer
cholangiocarcinoma of the gallbladder
unresectable extrahepatic bile duct cancer
recurrent extrahepatic bile duct cancer
cholangiocarcinoma of the extrahepatic bile duct
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
stage IV pancreatic cancer
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining gemcitabine, fluorouracil, and leucovorin in treating patients with recurrent, refractory, or metastatic solid tumors or lymphomas.

Detailed description: OBJECTIVES:

* Determine the clinical toxic effects associated with administering sequential gemcitabine followed by fluorouracil with leucovorin calcium in patients with refractory or recurrent or metastatic solid tumors or lymphomas.
* Determine achieved steady-state plasma levels of gemcitabine and fluorouracil in these patients.
* Determine any antitumor activity of this regimen in these patients.
* Determine the pharmacodynamics of gemcitabine and fluorouracil in these patients.

OUTLINE: This is a dose-escalation study of fluorouracil and gemcitabine.

During the first course, patients receive gemcitabine IV over 30 minutes once weekly for 2 weeks followed by one week of rest. During subsequent courses, patients receive gemcitabine as above followed immediately by fluorouracil IV over 24 hours once weekly for 2 weeks. Patients also receive leucovorin calcium orally on days 1 and 8 and IV on days 2 and 9. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Sequential dose escalation of fluorouracil is followed by sequential dose escalation of gemcitabine. Cohorts of 3-6 patients receive escalating doses of fluorouracil and then gemcitabine until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose preceding that at which 2 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A maximum of 108 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of cancer that has failed standard therapy or for which no such therapy exists, including, but not limited to:

  * Unresectable primary or recurrent solid tumors (e.g., colon, pancreatic, lung, esophageal, or cholangiocarcinoma)
  * Metastatic disease
  * Lymphoma with no prior high-dose chemotherapy requiring autologous or allogeneic stem cell rescue
* No leukemias
* No CNS metastases or primary CNS malignancies
* No failure on prior gemcitabine therapy

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Absolute granulocyte count at least 2,000/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 2.0 mg/dL
* Transaminases less than 6 times upper limit of normal

Renal:

* Creatinine no greater than 2.0 mg/dL

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other serious concurrent medical illness that would preclude study
* No active infections requiring IV antibiotics
* HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* See Disease Characteristics
* More than 4 weeks since prior immunotherapy and recovered

Chemotherapy:

* See Disease Characteristics
* More than 4 weeks since prior chemotherapy (at least 6 weeks for mitomycin or nitrosoureas) and recovered
* At least 3 months since prior suramin
* At least 5 weeks since prior eniluracil (8 weeks prior to start of fluorouracil) and recovered

Endocrine therapy:

* No steroid therapy if utilized for chronic lymphoma therapy
* At least 4 weeks since prior steroidal therapy as disease treatment

Radiotherapy:

* At least 2 weeks since prior radiotherapy to no more than 20% of bone marrow
* At least 4 weeks since prior radiotherapy to 21% or more of bone marrow
* Recovered from prior radiotherapy

Surgery:

* Recovered from prior surgery

Other:

* No concurrent cimetidine

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Eva Szabo, MD
role: STUDY_CHAIR
References:
citation: Wright MA, Schuler B, Szabo E, Grem JL. Sustained partial response of an intra-abdominal desmoid tumor treated with gemcitabine, 5-fluorouracil and leucovorin. Ann Oncol. 2003 Apr;14(4):659-60. doi: 10.1093/annonc/mdg155. No abstract available.