Gemcitabine and Irinotecan in Treating Patients With Cancer of Unknown Primary

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00066781
First received: August 6, 2003
Last updated: June 17, 2012
Last verified: March 2009
  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 2

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:


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: April 2008 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
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:
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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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: June 17, 2012
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
Neoplasm Metastasis
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplastic Processes
Pathologic Processes
Gemcitabine
Irinotecan
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014