Sarcoma
Conditions
Keywords
adult neurofibrosarcoma, stage III adult soft tissue sarcoma, recurrent adult soft tissue sarcoma, stage II adult soft tissue sarcoma, stage IV adult soft tissue sarcoma
Brief summary
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: This phase II trial is studying how well erlotinib works in treating patients with unresectable or metastatic malignant peripheral nerve sheath tumor.
Detailed description
OBJECTIVES: * Determine response (confirmed, complete, and partial) in patients with unresectable or metastatic malignant peripheral nerve sheath tumor when treated with erlotinib. * Determine the qualitative and quantitative toxic effects of this drug in these patients. * Correlate, preliminarily, indicators of epidermal growth factor receptor (EGFR) function (e.g., expression, phosphorylation, or markers of signal transduction downstream of EGFR) with response and progression-free and overall survival in patients treated with this drug. * Determine the feasibility of accruing these patients in the cooperative group setting. OUTLINE: This is a multicenter study. Patients receive oral erlotinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a confirmed partial response and become resectable undergo surgical resection (with or without radiotherapy) and then receive 2 additional courses of erlotinib. Patients with responding disease who do not become resectable continue erlotinib as above. Patients achieving a complete response (CR) receive 2 additional courses of erlotinib beyond the CR. Patients are followed every 6 months for 2 years and then annually for 3 years. PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study.
Interventions
DRUGerlotinib hydrochloride
150 mg per day, daily until disease progression
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed malignant peripheral nerve sheath tumor * Malignant schwannoma or neurofibrosarcoma * Clinical evidence of unresectable or metastatic disease * Measurable disease * No known current CNS metastases PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Zubrod 0-2 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count greater than 1,500/mm\^3 * Platelet count greater than 100,000/mm\^3 Hepatic * Bilirubin less than 1.5 times upper limit of normal (ULN) * SGOT or SGPT less than 1.5 times ULN (5 times ULN for patients with documented liver metastases) Renal * Creatinine no greater than 1.5 times ULN * Creatinine clearance greater than 60 mL/min Ophthalmic * No known history of any of the following corneal diseases: * Dry eye syndrome * Sjögren's syndrome * Keratoconjunctivitis sicca * Exposure keratopathy * Fuch's dystrophy * No other active disorders of the cornea Gastrointestinal * No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation * No active peptic ulcer disease * No intractable nausea or vomiting * Able to swallow medications OR receive enteral medications via gastrostomy feeding tube Other * Not pregnant or nursing * Fertile patients must use effective contraception * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy * More than 28 days since prior biologic therapy for this malignancy Chemotherapy * More than 28 days since prior chemotherapy for this malignancy Endocrine therapy * Not specified Radiotherapy * More than 60 days since prior radiotherapy to the target lesion with subsequent documented progression * More than 60 days since prior radiofrequency ablation to the target lesion with subsequent documented progression * No concurrent radiotherapy Surgery * At least 3 weeks since prior major surgery and recovered * No prior surgical procedure affecting absorption Other * More than 28 days since prior investigational drugs for this malignancy * More than 60 days since prior embolization to the target lesion with subsequent documented progression * No prior epidermal growth factor receptor-targeting therapy * No concurrent antiretroviral therapy for HIV-positive patients * No other concurrent investigational or commercial agents or therapies for the malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patients With Response (Confirmed Complete, and Partial) With Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumor When Treated With Erlotinib. | 25 weeks | Complete response - Complete disappearance of all measurable and non-measurable disease. No new lesions, no disease related symptoms, normalization of markers and other abnormal lab values. Partial response - Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease, no new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity | Up to 25 weeks | Only adverse events that are possibly, probably or definitely related to study drug are reported. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Correlate, Preliminarily, Indicators of Epidermal Growth Factor Receptor (EGFR) Function With Response and Progression-free and Overall Survival in Patients Treated With This Drug. | — | NOT COMPLETED DUE TO EARLY CLOSURE OF STUDY |
| Feasibility of Accruing These Patients in the Cooperative Group Setting | — | NOT COMPLETED DUE TO EARLY CLOSURE OF STUDY |
Countries
United States
Participant flow
Pre-assignment details
Four patients enrolled to study were found to be ineligible. One patient did not have measurable disease, one patient had radiotherapy 19 days prior to registration and two patients were found ineligible upon pathology review.
Participants by arm
| Arm | Count |
|---|---|
| Arm I (OSI-774) OSI-774 150 mg daily for 25 weeks | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Arm I (OSI-774) |
|---|---|
| Age, Continuous | 45.3 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Prior multi-agent chemotherapy No | 6 Participants |
| Prior multi-agent chemotherapy Yes | 14 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 20 |
| serious Total, serious adverse events | 12 / 20 |
Outcome results
Primary
Patients With Response (Confirmed Complete, and Partial) With Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumor When Treated With Erlotinib.
Complete response - Complete disappearance of all measurable and non-measurable disease. No new lesions, no disease related symptoms, normalization of markers and other abnormal lab values. Partial response - Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease, no new lesions.
Time frame: 25 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (OSI-774) | Patients With Response (Confirmed Complete, and Partial) With Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumor When Treated With Erlotinib. | 0 Participants |
Secondary
Toxicity
Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Up to 25 weeks
Population: All participants receiving at least some protocol treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (OSI-774) | Toxicity | Anorexia | 1 Participants |
| Arm I (OSI-774) | Toxicity | Diarrhea | 1 Participants |
| Arm I (OSI-774) | Toxicity | Dyspnea (shortness of breath) | 1 Participants |
| Arm I (OSI-774) | Toxicity | Fatigue (asthenia, lethargy, malaise) | 3 Participants |
| Arm I (OSI-774) | Toxicity | Hemoglobin | 1 Participants |
| Arm I (OSI-774) | Toxicity | Nausea | 1 Participants |
| Arm I (OSI-774) | Toxicity | Pain - Abdomen NOS | 1 Participants |
| Arm I (OSI-774) | Toxicity | Pruritus/itching | 1 Participants |
| Arm I (OSI-774) | Toxicity | Somnolence/depressed level of consciousness | 1 Participants |
| Arm I (OSI-774) | Toxicity | Vision-blurred vision | 1 Participants |
| Arm I (OSI-774) | Toxicity | Rash/desquamation | 1 Participants |
Other Pre-specified
Correlate, Preliminarily, Indicators of Epidermal Growth Factor Receptor (EGFR) Function With Response and Progression-free and Overall Survival in Patients Treated With This Drug.
NOT COMPLETED DUE TO EARLY CLOSURE OF STUDY
Other Pre-specified
Feasibility of Accruing These Patients in the Cooperative Group Setting
NOT COMPLETED DUE TO EARLY CLOSURE OF STUDY