Imatinib Mesylate in Treating Patients With Progressive, Refractory, or Recurrent Stage II or Stage III Testicular or Ovarian Cancer

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00042952

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have progressive, refractory, or recurrent stage II or stage III testicular cancer or stage II or stage III ovarian cancer following cisplatin-based chemotherapy

Condition or Disease	Intervention/Treatment	Phase
Ovarian Dysgerminoma Recurrent Malignant Testicular Germ Cell Tumor Recurrent Ovarian Germ Cell Tumor Stage II Malignant Testicular Germ Cell Tumor Stage II Ovarian Germ Cell Tumor Stage III Malignant Testicular Germ Cell Tumor Stage III Ovarian Germ Cell Tumor Testicular Seminoma	Drug: imatinib mesylate Procedure: therapeutic conventional surgery Other: laboratory biomarker analysis	Phase 2

Detailed Description

OBJECTIVES:

Determine the activity of imatinib mesylate in patients with progressive, refractory, or recurrent pure testicular seminoma or ovarian germ cell dysgerminoma after cisplatin-based chemotherapy.
Determine the toxicity of this drug in this patient population. III. Determine KIT expression and identify mutations in the c-kit gene in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral imatinib mesylate once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who achieve a partial response or stable disease with normalization of human chorionic gonadotropin may undergo surgical resection of residual lesions at each tumor status assessment. If residual viable germ cell tumor is present in the resected specimen, patients may resume imatinib mesylate. If no viable germ cell tumor is present in the resected specimen, then no further therapy is administered.

Patients are followed every 3 months for 1 year and then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 32 patients will be accrued for this study within 32-38 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study Of Imatinib Mesylate (Gleevec, Formerly Known As STI571; IND 61,135, NSC #716051) In Patients With Refractory Seminoma

Study Start Date :

Jun 1, 2002

Actual Primary Completion Date :

Oct 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (imatinib mesylate and surgical resection) Patients receive oral imatinib mesylate once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who achieve a partial response or stable disease with normalization of human chorionic gonadotropin may undergo surgical resection of residual lesions at each tumor status assessment. If residual viable germ cell tumor is present in the resected specimen, patients may resume imatinib mesylate. If no viable germ cell tumor is present in the resected specimen, then no further therapy is administered.	Drug: imatinib mesylate Given orally Other Names: CGP 57148 Gleevec Glivec Procedure: therapeutic conventional surgery Undergo surgical resection Other: laboratory biomarker analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (imatinib mesylate and surgical resection)

Drug: imatinib mesylate

Given orally

Other Names:

CGP 57148

Gleevec

Glivec

Procedure: therapeutic conventional surgery

Undergo surgical resection

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

Response rate defined as either a complete or partial response using RECIST criteria [Up to 2 years]
Response rate (CR+PR) and exact 95% confidence interval based on the binomial distribution for the response rate will be computed.

Secondary Outcome Measures

Grade 1 or higher toxicities assessed using CTC)version 2 [Up to 2 years]
Toxicities will be tabulated.
Duration of response [From first response (CR or PR) to the date of disease progression or death, assessed up to 2 years]
The Kaplan-Meier product-limit method will be used.
Disease-free survival [From the date of initiation of treatment to date of progression or death due to any cause, whichever occurs first, assessed up to 2 years]
The Kaplan-Meier product-limit method will be used.
Overall survival [From date of initiation of treatment to date of death due to any cause, assessed up to 2 years]
The Kaplan-Meier product-limit method will be used.
Proportion of patients with mutations in the c-KIT gene [Up to 2 years]
The 95% confidence interval will be estimated.

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed pure testicular seminoma or ovarian germ cell dysgerminoma
Histologic documentation of metastatic/recurrent disease not required
Alpha-fetoprotein level must be normal, unless abnormal level is explained by other conditions and approved by the study chair
Clinical stage II or III
Progressive, refractory, or recurrent disease, meeting at least 1 of the following criteria:
Measurable progressive disease
Biopsy-proven residual disease
Persistently elevated or rising B-human chorionic gonadotropin (HCG) titers, defined as at least 2 values above the upper limit of normal (ULN)
Cisplatin-refractory disease without option of potentially curative therapy, meeting 1 of the following criteria:
Failed high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) or autologous bone marrow transplantation (AuBMT)
Ineligible for or refused PBSCT or AuBMT
Unlikely to achieve long-term benefit from PBSCT or AuBMT
Current evidence of metastatic disease
Unidimensionally measurable target lesions
At least 20 mm by conventional techniques (e.g., physical examination for clinically palpable lymph nodes and superficial skin lesions or chest x-ray for clearly defined lung lesions surrounded by aerated lung)
At least 10 mm by spiral CT scan or MRI
If measurable disease is confined to a solitary lesion, then its neoplastic nature must be confirmed by histology
Ultrasound may not be used to measure tumor lesions that are not easily accessible clinically
Non-measurable/non-target lesions, with HCG at least ULN, including the following:
Bone lesions
Pleural or pericardial effusions
Ascites
CNS lesions
Leptomeningeal disease
Irradiated lesions, unless progression documented after radiotherapy
Performance status - ECOG 0-2
Granulocyte count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 9 g/dL (transfusion allowed)
Bilirubin no greater than 1.5 times upper limit of normal (ULN)
SGOT/SGPT no greater than 2.5 times ULN
Creatinine no greater than 1.5 times ULN
No other severe and/or uncontrolled concurrent medical illness
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for 3 months after study participation
See Disease Characteristics
See Disease Characteristics
At least 4 weeks since prior chemotherapy
No concurrent chemotherapy
No concurrent hormonal therapy except steroids for adrenal failure, hormones for non-disease-related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic
See Disease Characteristics
At least 4 weeks since prior radiotherapy
Prior radiotherapy to a symptomatic lesion or one that may produce disability (e.g., unstable femur) allowed
No concurrent palliative radiotherapy
No concurrent grapefruit juice
No concurrent warfarin for therapeutic anticoagulation (concurrent mini-dose warfarin [1 mg orally per day] as prophylaxis allowed)