17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: AIDS-related Peripheral/Systemic Lymphoma; Stage IV Small Lymphocytic Lymphoma; Chondrosarcoma; Stage IV Marginal Zone Lymphoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Splenic Marginal Zone Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Small Intestine Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Uterine Sarcoma; Angioimmunoblastic T-cell Lymphoma; Metastatic Osteosarcoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Grade 2 Follicular Lymphoma; AIDS-related Primary CNS Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult Burkitt Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Ovarian Sarcoma; Recurrent Adult Hodgkin Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Recurrent Osteosarcoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Anaplastic Large Cell Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Intraocular Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Stage IV Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Stage IV Uterine Sarcoma; Stage IV Adult Burkitt Lymphoma; Stage IV Mantle Cell Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Stage IV Grade 1 Follicular Lymphoma

Treatments: Other: pharmacological study; Drug: tanespimycin

Study type: Interventional

Funder types: NIH

Identifiers

NCT00004241

PCI-99-020

U01CA099168 (U.S. NIH Grant/Contract)

CDR0000067486 (Registry Identifier)

NCI-2012-02315

Details and patient eligibility

About

Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin in treating patients with advanced epithelial cancer, malignant lymphoma, or sarcoma

Full description

PRIMARY OBJECTIVES:

I. Determine the dose-limiting toxicity and maximum tolerated dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) in patients with advanced epithelial cancer, malignant lymphoma, or sarcoma.

II. Determine the significant toxic effects associated with this drug in these patients.

III. Determine the response in patients treated with this drug. IV. Determine the pharmacokinetics of 17-AAG and 17AG in these patients.

OUTLINE: This is a dose-escalation study. Patients receive treatment according to 1 of 2 schedules.

Schedule B: Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 1-2 hours twice weekly for 3 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Schedule C: Patients receive 17-AAG IV over 1-2 hours twice weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

In both schedules, cohorts of 3-6 patients receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. At least 6 patients receive treatment at the MTD.

PROJECTED ACCRUAL: A maximum of 60 patients will be accrued for this study.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Histologically confirmed advanced epithelial cancer, malignant lymphoma, or sarcoma for which no standard curative therapy exists
• Brain metastases allowed after definitive radiotherapy
• Performance status - ECOG 0-2
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 mg/dL
• SGOT no greater than 2 times normal
• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for at least 1 week before, during, and for at least 2 weeks after study completion
• No active infection
• No other serious concurrent condition
• No prior allergic reaction to egg products
• At least 4 weeks since prior biologic therapy (regional or systemic)
• At least 4 weeks since prior chemotherapy
• See Disease Characteristics
• At least 4 weeks since prior radiotherapy

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Schedule B (tanespimycin)

Experimental group

Description:

Patients receive 17-AAG IV over 1-2 hours twice weekly for 3 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: tanespimycin

Other: pharmacological study

Schedule C (tanespimycin)

Experimental group

Description:

Patients receive 17-AAG IV over 1-2 hours twice weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: tanespimycin

Other: pharmacological study