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Gemcitabine and Irinotecan in Treating Patients With Cancer of Unknown Primary

Primary Purpose

Carcinoma of Unknown Primary

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
gemcitabine hydrochloride
irinotecan hydrochloride
Sponsored by
Alliance for Clinical Trials in Oncology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma of Unknown Primary focused on measuring adenocarcinoma of unknown primary, newly diagnosed carcinoma of unknown primary, squamous cell carcinoma of unknown primary, undifferentiated carcinoma of unknown primary

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mercy Cancer Center at Mercy Medical Center - North Iowa
  • Mayo Clinic Cancer Center
  • Cancer Resource Center - Lincoln
  • CCOP - Missouri Valley Cancer Consortium

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort I (closed to accrual 11/17/05)

Cohort II

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Confirmed Response Rate (Partial or Complete Response for 2 Consecutive Evaluations at Least 4 Weeks Apart) as Measured by RECIST Criteria
The primary endpoint is confirmed response rate. If measurable disease is present, a confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. All registered patients meeting the eligibility criteria that have signed a consent form and have begun treatment will be evaluable for response.

Secondary Outcome Measures

Overall Survival
Overall survival time is defined as the time from registration to death due> to any cause. The distribution of survival time will be estimated using> the method of Kaplan-Meier . Overall survival will be calculated for> all evaluable patients combined and by group (ie. for patients with or> without the UGT1A1*28 polymorphism).
Time to Disease Progression
Time to disease progression is defined as the time from registration to documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression on day 1 post-registration. The distribution of time to progression will be estimated using the method of Kaplan-Meier. Time to disease progression will be calculated for all evaluable patients combined and by group (ie. for patients with or without the UGT1A1*28 polymorphism).

Full Information

First Posted
August 6, 2003
Last Updated
February 17, 2017
Sponsor
Alliance for Clinical Trials in Oncology
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00066781
Brief Title
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

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
February 2004 (undefined)
Primary Completion Date
April 2008 (Actual)
Study Completion Date
March 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alliance for Clinical Trials in Oncology
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort I (closed to accrual 11/17/05)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort II
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
irinotecan hydrochloride
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Confirmed Response Rate (Partial or Complete Response for 2 Consecutive Evaluations at Least 4 Weeks Apart) as Measured by RECIST Criteria
Description
The primary endpoint is confirmed response rate. If measurable disease is present, a confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. All registered patients meeting the eligibility criteria that have signed a consent form and have begun treatment will be evaluable for response.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Overall survival time is defined as the time from registration to death due> to any cause. The distribution of survival time will be estimated using> the method of Kaplan-Meier . Overall survival will be calculated for> all evaluable patients combined and by group (ie. for patients with or> without the UGT1A1*28 polymorphism).
Time Frame
Up to 2 years
Title
Time to Disease Progression
Description
Time to disease progression is defined as the time from registration to documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression on day 1 post-registration. The distribution of time to progression will be estimated using the method of Kaplan-Meier. Time to disease progression will be calculated for all evaluable patients combined and by group (ie. for patients with or without the UGT1A1*28 polymorphism).
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew P. Goetz, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Study Chair
Facility Information:
Facility Name
Mercy Cancer Center at Mercy Medical Center - North Iowa
City
Mason City
State/Province
Iowa
ZIP/Postal Code
50401
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Cancer Resource Center - Lincoln
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68510
Country
United States
Facility Name
CCOP - Missouri Valley Cancer Consortium
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68106
Country
United States

12. IPD Sharing Statement

Citations:
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.
Results Reference
result
PubMed Identifier
22815703
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.
Results Reference
derived

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Gemcitabine and Irinotecan in Treating Patients With Cancer of Unknown Primary

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