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S0331: Imatinib Mesylate in Treating Patients With Metastatic or Unresectable Merkel Cell Cancer

Primary Purpose

Recurrent Neuroendocrine Carcinoma of the Skin, Stage II Neuroendocrine Carcinoma of the Skin, Stage III Neuroendocrine Carcinoma of the Skin

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
imatinib mesylate
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Neuroendocrine Carcinoma of the Skin

Eligibility Criteria

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

Inclusion Criteria: Patients must have a biopsy-proven diagnosis of Merkel Cell Carcinoma (Cutaneous Neuroendocrine Carcinoma) that is distantly metastatic or unresectable Tumors must beet BOTH of the following criteria: The primary must be of skin origin; (patients with unknown primary are not eligible) All patients must have immunohistochemical staining with c-kit (CD117) expression by tumor documented by DAKO, Benchmark, or similar staining kit The institution must plan to submit materials for pathology review NOTE: Submission of additional specimens is strongly encouraged Patients must have measurable disease; all measurable lesions must be assessed (by physical examination, CT or MRI scan or plain X-ray) within 28 days prior to registration; tests to assess non-measurable disease must be performed within 42 days prior to registration Patients with symptomatic, unstable or untreated brain metastases are not eligible; previous treatment must have been completed at least 28 days prior to registration Patients must have a Zubrod performance status of 0-2 Patients must not have received radiotherapy, chemotherapy, biologic therapy or any other investigational drug for any reason within 28 days prior to registration; all toxicities from prior treatment must have been resolved (in the opinion of the treating investigator); patients whose only disease is within a previous radiation therapy port must demonstrate clearly progressive disease prior to registration; patients must have resolution of all toxicities from any prior therapy to =< grade 1 (CTCAE version 3.0); patients must not have had a major surgery (e.g., large chest and abdominal incisions, major soft tissue resections) within 14 days prior to registration Serum bilirubin =< 3 x the institutional upper limit of normal (including those with hepatic metastases) SGOT or SGPT =< 2.5 x the institutional upper limit of normal (or =< 5 x the institutional upper limit of normal if hepatic metastases is present) Serum creatinine =< 1.5 x the institutional upper limit of normal ANC >= 1,000/ul Platelet count >= 100,000/ul Hemoglobin >= 9 gm/dl (this may be achieved by transfusion if needed) Patient must not have class 3/4 cardiac problems as defined by the New York Heart Association criteria (e.g., congestive heart failure, myocardial infarction within 2 months of study) Patient must not have a sever and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, or active uncontrolled infection, e.g., HIV) Patients must not be pregnant or nursing; for women of reproductive potential, a negative serum pregnancy test must be done within 7 days prior to registration; post-menopausal women who have not had their ovaries removed must be amenorrheic for at least 12 months to be considered of non-childbearing potential; patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug NOTE: oral contraceptives may interact with the study drug and should be used with caution Patients must not be taking therapeutic doses of Coumadin (warfarin) as anticoagulation at the time of registration; patients requiring therapeutic anticoagulation may use low molecular weight heparin (e.g., Lovenox) or other agents, and mini-dose Coumadin (1 mg po QD) as prophylaxis is allowed If day 7, 14, or 42 falls on a weekend or holiday, the limit may be extended to the next working day In calculating days of tests and measurements, the day a test or measurement is dose is considered day 0; therefore, if a test is done on a Monday, the Monday two weeks later would be considered day 14; this allows for efficient patient scheduling without exceeding the guidelines No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base

Sites / Locations

  • Southwest Oncology Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

Patients receive oral imatinib mesylate once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression, unacceptable toxicity, or symptomatic deterioration.

Outcomes

Primary Outcome Measures

Response probability

Secondary Outcome Measures

Toxicity rates
Estimated with 95% confidence interval.
Mutation rate for KIT
Estimated with 95% confidence interval.
Mutation rate for PDGFRA
Estimated with 95% confidence interval.
Mutation rate for PDGFRB
Estimated with 95% confidence intervals.

Full Information

First Posted
September 10, 2003
Last Updated
February 27, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00068783
Brief Title
S0331: Imatinib Mesylate in Treating Patients With Metastatic or Unresectable Merkel Cell Cancer
Official Title
A Phase II Trial of STI-571/Imatinib (Gleevec®) (NSC-716051) in Neuroendocrine Carcinoma of the Skin (Merkel Cell Carcinoma)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
October 2003 (undefined)
Primary Completion Date
June 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase II trial is studying how well imatinib mesylate works in treating patients with metastatic or unresectable Merkel cell cancer. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth
Detailed Description
PRIMARY OBJECTIVES: I. To assess the feasibility of a Southwest Oncology Group Phase II trial or oral STI-571/imatinib (Gleevec) administered to patients with metastatic or unresectable Merkel cell carcinoma. II. To evaluate the objective response probability (confirmed and unconfirmed complete and partial responses) of oral STI-571/imatinib (Gleevec) administered to patients with metastatic or unresectable Merkel cell carcinoma. III. To assess qualitative and quantitative toxicities of oral STI-581/imatinib (Gleevec) administered to patients with metastatic or unresectable Merkel cell carcinoma. IV. To analyze tumor samples for activating mutations of STI-571/imatinib-sensitive kinases (KIT, PDGFRA, PDGFRB) by denaturing HPLC and direct DNA sequencing. OUTLINE: This is a multicenter study. Patients receive oral imatinib mesylate once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression, unacceptable toxicity, or symptomatic deterioration. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Neuroendocrine Carcinoma of the Skin, Stage II Neuroendocrine Carcinoma of the Skin, Stage III Neuroendocrine Carcinoma of the Skin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
Patients receive oral imatinib mesylate once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression, unacceptable toxicity, or symptomatic deterioration.
Intervention Type
Drug
Intervention Name(s)
imatinib mesylate
Other Intervention Name(s)
CGP 57148, Gleevec, Glivec
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Response probability
Time Frame
Up to 4 years
Secondary Outcome Measure Information:
Title
Toxicity rates
Description
Estimated with 95% confidence interval.
Time Frame
Up to 4 years
Title
Mutation rate for KIT
Description
Estimated with 95% confidence interval.
Time Frame
Baseline
Title
Mutation rate for PDGFRA
Description
Estimated with 95% confidence interval.
Time Frame
Baseline
Title
Mutation rate for PDGFRB
Description
Estimated with 95% confidence intervals.
Time Frame
Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have a biopsy-proven diagnosis of Merkel Cell Carcinoma (Cutaneous Neuroendocrine Carcinoma) that is distantly metastatic or unresectable Tumors must beet BOTH of the following criteria: The primary must be of skin origin; (patients with unknown primary are not eligible) All patients must have immunohistochemical staining with c-kit (CD117) expression by tumor documented by DAKO, Benchmark, or similar staining kit The institution must plan to submit materials for pathology review NOTE: Submission of additional specimens is strongly encouraged Patients must have measurable disease; all measurable lesions must be assessed (by physical examination, CT or MRI scan or plain X-ray) within 28 days prior to registration; tests to assess non-measurable disease must be performed within 42 days prior to registration Patients with symptomatic, unstable or untreated brain metastases are not eligible; previous treatment must have been completed at least 28 days prior to registration Patients must have a Zubrod performance status of 0-2 Patients must not have received radiotherapy, chemotherapy, biologic therapy or any other investigational drug for any reason within 28 days prior to registration; all toxicities from prior treatment must have been resolved (in the opinion of the treating investigator); patients whose only disease is within a previous radiation therapy port must demonstrate clearly progressive disease prior to registration; patients must have resolution of all toxicities from any prior therapy to =< grade 1 (CTCAE version 3.0); patients must not have had a major surgery (e.g., large chest and abdominal incisions, major soft tissue resections) within 14 days prior to registration Serum bilirubin =< 3 x the institutional upper limit of normal (including those with hepatic metastases) SGOT or SGPT =< 2.5 x the institutional upper limit of normal (or =< 5 x the institutional upper limit of normal if hepatic metastases is present) Serum creatinine =< 1.5 x the institutional upper limit of normal ANC >= 1,000/ul Platelet count >= 100,000/ul Hemoglobin >= 9 gm/dl (this may be achieved by transfusion if needed) Patient must not have class 3/4 cardiac problems as defined by the New York Heart Association criteria (e.g., congestive heart failure, myocardial infarction within 2 months of study) Patient must not have a sever and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, or active uncontrolled infection, e.g., HIV) Patients must not be pregnant or nursing; for women of reproductive potential, a negative serum pregnancy test must be done within 7 days prior to registration; post-menopausal women who have not had their ovaries removed must be amenorrheic for at least 12 months to be considered of non-childbearing potential; patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug NOTE: oral contraceptives may interact with the study drug and should be used with caution Patients must not be taking therapeutic doses of Coumadin (warfarin) as anticoagulation at the time of registration; patients requiring therapeutic anticoagulation may use low molecular weight heparin (e.g., Lovenox) or other agents, and mini-dose Coumadin (1 mg po QD) as prophylaxis is allowed If day 7, 14, or 42 falls on a weekend or holiday, the limit may be extended to the next working day In calculating days of tests and measurements, the day a test or measurement is dose is considered day 0; therefore, if a test is done on a Monday, the Monday two weeks later would be considered day 14; this allows for efficient patient scheduling without exceeding the guidelines No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wolfram Samlowski
Organizational Affiliation
SWOG Cancer Research Network
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southwest Oncology Group
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78245
Country
United States

12. IPD Sharing Statement

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S0331: Imatinib Mesylate in Treating Patients With Metastatic or Unresectable Merkel Cell Cancer

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