Gemcitabine and Irinotecan in Treating Patients With Cancer of Unknown Primary

Carcinoma of Unknown Primary Clinical Trial

Official title:

A Phase II Study Of Gemcitabine (GEMZAR) And Irinotecan (CPT-11) In Previously Untreated Patients With Measurable Disease With Unknown Primary Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00066781
• Other study ID #: NCCTG-N004E
• Secondary ID: NCI-2011-01592CD
• Status: Completed
• Phase: Phase 2
• First received: August 6, 2003
• Last updated: August 12, 2016
• Start date: February 2004
• Est. completion date: March 2009

Study information

• Verified date: August 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: March 2009
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma of Unknown Primary
• Neoplasms, Unknown Primary

Intervention

Drug:
• gemcitabine hydrochloride
Given IV
• irinotecan hydrochloride
Given IV

Locations

Country	Name	City	State
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Mayo Clinic Cancer Center	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed response rate (partial or complete response for 2 consecutive evaluations at least 4 weeks apart) as measured by RECIST criteria		Up to 2 years	No
Secondary	Overall survival periodically for up to 2 years from registration		Up to 2 years	No
Secondary	Time to disease progression periodically for up to 2 years from registration		Up to 2 years	No
Secondary	Adverse event rates assessed by NCI common toxicity criteria for adverse events (CTCAE v3.0) at all courses		Up to 2 years	Yes