Clinical trial NCT00066781: Gemcitabine and Irinotecan in Treating Patients With Cancer of Unknown Primary
Official title: A Phase II Study Of Gemcitabine (GEMZAR) And Irinotecan (CPT-11) In Previously Untreated Patients With Measurable Disease With Unknown Primary Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma of Unknown Primary
Keywords: adenocarcinoma of unknown primary
newly diagnosed carcinoma of unknown primary
squamous cell carcinoma of unknown primary
undifferentiated carcinoma of unknown primary
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-08-07
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Confirmed Response Rate (Partial or Complete Response for 2 Consecutive Evaluations at Least 4 Weeks Apart) as Measured by RECIST Criteria
timeFrame: Up to 2 years
Secondary outcomes:
measure: Overall Survival
timeFrame: Up to 2 years
measure: Time to Disease Progression
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Mason City
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - North Iowa
state: Iowa
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Lincoln
country: United States
facility: Cancer Resource Center - Lincoln
state: Nebraska
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
Study officials:
affiliation: Mayo Clinic
name: Matthew P. Goetz, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.