A Phase II Study Of Gemcitabine (GEMZAR) And Irinotecan (CPT-11) In Previously Untreated Patients With Measurable Disease With Unknown Primary Carcinoma
18 Years
N/A
Both
Carcinoma of Unknown Primary
Trial Information
A Phase II Study Of Gemcitabine (GEMZAR) And Irinotecan (CPT-11) In Previously Untreated Patients With Measurable Disease With Unknown Primary Carcinoma
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Confirmed response rate (partial or complete response for 2 consecutive evaluations at least 4 weeks apart) as measured by RECIST criteria
Safety Issue:
No
Principal Investigator
Matthew P. Goetz, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Federal Government
Study ID:
CDR0000318830
NCT ID:
NCT00066781
Start Date:
February 2004
Completion Date:
Related Keywords:
- Carcinoma of Unknown Primary
- adenocarcinoma of unknown primary
- newly diagnosed carcinoma of unknown primary
- squamous cell carcinoma of unknown primary
- undifferentiated carcinoma of unknown primary
- Carcinoma
- Neoplasms, Unknown Primary
Name | Location |
|---|---|
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| CCOP - Missouri Valley Cancer Consortium | Omaha, Nebraska 68131 |
| Mercy Cancer Center at Mercy Medical Center - North Iowa | Mason City, Iowa 50401 |
| Cancer Resource Center - Lincoln | Lincoln, Nebraska 68510 |
