Gemcitabine and Irinotecan in Treating Patients With Cancer of Unknown Primary
This study has been completed.
Sponsor:
North Central Cancer Treatment Group
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
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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:
MedlinePlus related topics:
Cancer
Drug Information available for:
Gemcitabine
Irinotecan
Irinotecan hydrochloride
Gemcitabine 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: | 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
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 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 May 16, 2013