Gemcitabine and Irinotecan in Treating Patients With Cancer of Unknown Primary

NCT ID: NCT00066781

Last Updated: 2017-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-02-29
• Study Completion Date: 2009-03-31

Brief Summary

RATIONALE: Drugs used in chemotherapy such as gemcitabine and irinotecan 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: This phase II trial is studying how well giving gemcitabine together with irinotecan works in treating patients with cancer of unknown primary origin.

Detailed Description

OBJECTIVES:

Primary

• Determine the response rate in patients with carcinoma of unknown primary when treated with gemcitabine and irinotecan.
• Determine the adverse event profile and tolerability of this regimen, based on the presence or absence of the UGT1A1*28 polymorphism, in these patients. (Cohort I closed to accrual 11/17/05)
• Determine the adverse event profile and tolerability of this regimen. (Cohort II)

Secondary

• Determine the time to progression and overall survival of patients treated with this regimen.
• Correlate patterns of immunohistochemical staining with response in patients treated with this regimen.
• Correlate variation in multiple different genes, whose protein products are involved in the uptake, metabolism, and distribution of these drugs, with clinical outcomes, in terms of response and toxicity, in these patients.
• Determine primary origin of cancer of unknown primary samples by completing a 92-gene RT-PCR cancer classification assay.
• Determine whether the 92-gene assay results are correlated with clinical response to gemcitabine and irinotecan.

OUTLINE:

• Cohort I (closed to accrual 11/17/05): Patients receive gemcitabine IV over 30 minutes and irinotecan IV over 90 minutes on days 1, 8, 15, and 22. Irinotecan dose may be escalated or de-escalated after course 1 depending on toxicity. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
• Cohort II: Patients receive gemcitabine IV over 30 minutes and irinotecan IV over 90 minutes on days 1, 8, and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years.

Conditions

Carcinoma of Unknown Primary

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort I (closed to accrual 11/17/05)

Patients receive gemcitabine IV over 30 minutes and irinotecan IV over 90 minutes on days 1, 8, 15, and 22. Irinotecan dose may be escalated or de-escalated after course 1 depending on toxicity. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

gemcitabine hydrochloride

Intervention Type: DRUG

Given IV

irinotecan hydrochloride

Intervention Type: DRUG

Given IV

Cohort II

Patients receive gemcitabine IV over 30 minutes and irinotecan IV over 90 minutes on days 1, 8, and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

gemcitabine hydrochloride

Intervention Type: DRUG

Given IV

irinotecan hydrochloride

Intervention Type: DRUG

Given IV

Interventions

gemcitabine hydrochloride

Given IV

Intervention Type: DRUG

irinotecan hydrochloride

Given IV

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Neuroendocrine tumors
• Women with axillary node involvement only
• Women with adenocarcinoma of the peritoneum
• Carcinoma involving only 1 site, with resectable tumor at that site
• Squamous cell carcinoma limited to cervical, supraclavicular, or inguinal lymph nodes
• Men with poorly differentiated mediastinal or retroperitoneal tumor with stains suggestive of germ cell origin or serum tumor markers (AFP/HCG)
• Men with prominent blastic bony metastases or markedly elevated prostate-specific antigen, suggesting prostate origin
• Must be willing to provide blood and tissue samples
• No brain or meningeal involvement

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin must meet 1 of the following criteria:

• Less than or equal to upper limit of normal (ULN) and no UGT1A1 genotyping is required
• Greater than ULN but less than 2 times ULN and UGT1A1 for 6/7 genotype or 7/7 genotype patients
• Alkaline phosphatase no greater than 3 times ULN
• AST no greater than 3 times ULN (5 times ULN if liver metastases are present)

Renal

• Creatinine no greater than 2.0 times ULN

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other invasive malignancy within the past 5 years
• No other severe concurrent disease that would make the patient inappropriate for the study in the judgment of the investigator
• No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent biologic agents
• No concurrent filgrastim (G-CSF)

Chemotherapy

• No prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to more than 25% of the bone marrow
• No concurrent radiotherapy

Surgery

• More than 4 weeks since prior major surgery

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew P. Goetz, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

Mercy Cancer Center at Mercy Medical Center - North Iowa

Mason City, Iowa, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Cancer Resource Center - Lincoln

Lincoln, Nebraska, United States

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Countries

United States

References

Holtan SG, Foster NR, Erlichman CE, et al.: Gemcitabine (G) and irinotecan (CPT-11) as first-line therapy for carcinoma (ca) of unknown primary (CUP): An NCCTG phase II trial. [Abstract] J Clin Oncol 26 (Suppl 15): A-13525, 2008.

Reference Type: RESULT

Holtan SG, Steen PD, Foster NR, Erlichman C, Medeiros F, Ames MM, Safgren SL, Graham DL, Behrens RJ, Goetz MP. Gemcitabine and irinotecan as first-line therapy for carcinoma of unknown primary: results of a multicenter phase II trial. PLoS One. 2012;7(7):e39285. doi: 10.1371/journal.pone.0039285. Epub 2012 Jul 17.

Reference Type: DERIVED

PMID: 22815703 (View on PubMed)

Other Identifiers

NCI-2011-01592

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000318830

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCCTG-N004E

Identifier Type: -

Identifier Source: org_study_id