Gemcitabine and Irinotecan in Treating Patients With Cancer of Unknown Primary - Full Text View

Sponsor:	North Central Cancer Treatment Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00066781

Purpose

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.

Condition	Intervention	Phase
Carcinoma of Unknown Primary	Drug: gemcitabine hydrochloride Drug: irinotecan hydrochloride	Phase II

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Study Of Gemcitabine (GEMZAR) And Irinotecan (CPT-11) In Previously Untreated Patients With Measurable Disease With Unknown Primary Carcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Gemcitabine Irinotecan U 101440E Gemcitabine hydrochloride Irinotecan hydrochloride

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Confirmed response rate (partial or complete response for 2 consecutive evaluations at least 4 weeks apart) as measured by RECIST criteria [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival periodically for up to 2 years from registration [ Designated as safety issue: No ]
Time to disease progression periodically for up to 2 years from registration [ Designated as safety issue: No ]
Adverse event rates assessed by NCI common toxicity criteria for adverse events (CTCAE v3.0) at all courses [ Designated as safety issue: Yes ]
Relationship between genetic variations and the clinical outcomes of response, adverse events, survival, and time to progression at baseline [ Designated as safety issue: Yes ]

Estimated Enrollment:	42
Study Start Date:	February 2004
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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.	Drug: gemcitabine hydrochloride Given IV Drug: irinotecan hydrochloride Given IV
Experimental: 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.	Drug: gemcitabine hydrochloride Given IV Drug: irinotecan hydrochloride Given IV

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.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed carcinoma of undetermined origin, with any of the following light microscopic diagnoses:
- Adenocarcinoma
  - Poorly differentiated non-small cell carcinoma
  - Poorly differentiated squamous cell carcinoma
Primary site not revealed by the following diagnostic tests:
- Complete history and physical
- Complete blood count and chemistries
- Chest x-ray and/or CT scan
- Abdominal CT scan
- Directed evaluation of symptomatic areas
- Mammogram in women
- Colonoscopy in patients with liver metastases to exclude a colon primary
- Hematoxylin and eosin (H&E) staining OR immunostaining if H&E results are unclear, including all of the following:
  - Keratin or epithelial membrane antigen
  - S-100 or HMB45
  - LCA (CD45)
  - Chromogranin or synaptophysin
  - Thyroid transcription factor 1
Measurable disease
Patients with any of the following conditions are not eligible:
- 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00066781

Locations

United States, Iowa
Mercy Cancer Center at Mercy Medical Center - North Iowa
Mason City, Iowa, United States, 50401
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Nebraska
Cancer Resource Center - Lincoln
Lincoln, Nebraska, United States, 68510
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Matthew P. Goetz, MD	Mayo Clinic
Investigator:	Preston D. Steen, MD	Roger Maris Cancer Center at MeritCare Hospital
Investigator:	Charles Erlichman, MD	Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

Responsible Party:	Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier:	NCT00066781 History of Changes
Other Study ID Numbers:	CDR0000318830, NCCTG-N004E
Study First Received:	August 6, 2003
Last Updated:	April 14, 2009
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of unknown primary
newly diagnosed carcinoma of unknown primary
squamous cell carcinoma of unknown primary
undifferentiated carcinoma of unknown primary

Additional relevant MeSH terms:

Carcinoma
Neoplasms, Unknown Primary
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Gemcitabine
Irinotecan
Camptothecin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012