17-AAG and Sorafenib in Treating Patients With Unresectable or Metastatic Solid Tumors

NCT00121264 | Completed Phase 1

• 6 other identifiers: NCI-2012-03194CDR434803C-28906972U01CA062487P30CA022453
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is studying the side effects and best dose of 17-AAG when given together with sorafenib in treating patients with unresectable or metastatic solid tumors. Drugs used in chemotherapy, such as 17-AAG, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving 17-AAG together with sorafenib may kill more tumor cells.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

• Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by NCI CTCAE version 3.0

  42 days

• DLT as assessed by NCI CTCAE version 3.0

  42 days

Secondary Outcomes (4)

• Pharmacokinetic parameters of sorafenib tosylate and tanespimycin

  At baseline, at 0.5, 1, 2, 3, 4, 6, 9, and 12 hours of day 1, at 0.5, 1, and 2 hours on day 15, at 24 and 48 hours on days 16 and 17

• Pharmacodynamic effects of sorafenib tosylate and tanespimycin on surrogate markers and tumor tissue signaling by Western blotting

  At baseline and at day -1, 14, and 18

• Change in blood flow using dynamic contract enhanced MRI

  At baseline, at days -3 to 1, and at days 15-22

• Antitumor activity of this combination according to RECIST

  Up to 60 days after completion of study treatment

Study Arms (1)

Treatment (sorafenib tosylate, tanespimycin)

EXPERIMENTAL

Patients receive oral sorafenib twice daily on days -14 to 28 in course 1 and on days 1-28 in all subsequent courses. Patients also receive 17-AAG IV over 3 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: sorafenib tosylate; Drug: tanespimycin; Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: magnetic resonance imaging

Interventions

sorafenib tosylate DRUG

Given orally

Also known as: BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar, SFN

Treatment (sorafenib tosylate, tanespimycin)

tanespimycin DRUG

Given IV

Also known as: 17-AAG

Treatment (sorafenib tosylate, tanespimycin)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (sorafenib tosylate, tanespimycin)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (sorafenib tosylate, tanespimycin)

magnetic resonance imaging PROCEDURE

Correlative studies

Also known as: MRI, NMR imaging, NMRI, nuclear magnetic resonance imaging

Treatment (sorafenib tosylate, tanespimycin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
• Prior chemotherapy is allowed; patients may not have received chemotherapy for 4 weeks prior to the initiation of study treatment and must have full recovery from the acute effects of any prior chemotherapy; patients must not have had nitrosoureas or mitomycin C for 6 weeks prior to initiation of study treatment
• Prior radiation therapy is allowed; patients must have completed radiation at least 4 weeks prior to initiation of study treatment; patients who have received prior radiation to 50% or more of their total marrow volume will be excluded
• Prior treatment with biologic systemic therapies is permitted except for 17-AAG or Bay 43-9006 administration; prior experimental therapies (non FDA-approved agents) and immunotherapies are allowed; patients may not have received these therapies for 4 weeks prior to the initiation of study treatment and must have =\< grade 2 residual toxicities from the effects of these therapies
• ECOG performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of \> 12 weeks
• Absolute neutrophil count \>= 1,500/uL
• Platelets \>= 100,000/uL
• Total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) =\< 2.5 x institutional upper limit of normal; for patients with hepatic metastases, AST/ALT =\< 5 x institutional upper limit of normal are permitted
• Creatinine =\< 1.5 x institutional upper limit of normal OR
• Creatinine clearance \>= 60 mL/min for patients with creatinine levels above 1.5 x institutional ULN
• Tumor evaluation studies such as CT scans/MRI/X-rays/PSA should be performed within 28 days of starting protocol therapy
• Patients are required to have DLCO of \>= 60% on pretreatment pulmonary function tests with no symptomatic pulmonary disease
• Women of child-bearing potential and all men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

You may not qualify if:

• Patients who have had chemotherapy, immunotherapy, biologic therapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from acute AEs due to agents administered more than 4 weeks earlier
• Patients who have received any other investigational agents within 28 days of study entry
• Patients may not receive any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study except for medications that are prescribed for supportive care but potentially may have anticancer effect (i.e. megestrol acetate, dexamethasone, bisphosphonates); these medications must have been started at least 1 month prior to enrollment on study; in addition, men receiving treatment for prostate cancer will be maintained at castrate levels of testosterone by continuation of luteinizing- releasing hormone agonists
• Patients with egg allergy are excluded as 17-AAG is formulated in egg phospholipid
• Patients with known, symptomatic brain metastases should be excluded from this clinical trial; patients with stable or asymptomatic brain metastases are eligible but should not be taking enzyme-inducing anticonvulsants and should be maintained on stable steroid doses
• Patients with symptomatic pulmonary disease requiring medication including the following: dyspnea, dyspnea on exertion, paroxysmal nocturnal dyspnea, oxygen requirement and significant pulmonary disease, including chronic obstructive/restrictive pulmonary disease
• Patients that meet the Medicare criteria for home oxygen
• Patients with a prior history of chest radiation
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension (persistently elevated BP) or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant and nursing women are excluded from this study
• HIV positive patients taking combination antiretroviral medications (HAART) would be excluded; HIV positive patients not being treated with anti-retroviral medications and otherwise meeting organ function criteria should be considered eligible
• Patients receiving CYP 3A4 inter active agent are eligible but should be studied carefully and where acceptable and appropriate substitutions of non-CYP interactive drugs should be undertaken; patients on therapeutic warfarin should be switched to LMW heparin; if appropriate a hematology consult should be obtained
• Patients with any impediment to swallowing tablets would be excluded
• Patients taking rifampin, St. John's wort and enzyme inducing anticonvulsant agents (e.g. phenytoin, phenobarbital) are excluded
• Patients with bleeding diathesis or patients taking oral anticoagulation with warfarin are excluded

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Interventions

Sorafenib; tanespimycin; Magnetic Resonance Spectroscopy

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Ulka Vaishampayan

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2005
• First Posted: July 21, 2005
• Study Start: March 1, 2005
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: June 17, 2014

Record last verified: 2013-01

Locations

US (1)