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A Phase I Dose-Escalation Study of Intravenous 17-allylaminogeldanamycin (17-AAG) [NSC 330507, IND# 57,966] and Oral BAY 43-9006 [NSC 724772, IND #69,896] Administered in Patients With Pretreated Advanced Solid Tumors

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

A Phase I Dose-Escalation Study of Intravenous 17-allylaminogeldanamycin (17-AAG) [NSC 330507, IND# 57,966] and Oral BAY 43-9006 [NSC 724772, IND #69,896] Administered in Patients With Pretreated Advanced Solid Tumors


I. To recommend a phase II dose for 17AAG (once weekly intravenously for 3 of 4 weeks), in
combination with BAY 43-9006 (twice daily orally), by determining the feasibility, safety,
dose limiting toxicities and the maximally tolerated dose.


I. To evaluate the modulation of pharmacodynamic effects and to investigate the interaction
between the two mechanisms of action when used in combination by: Studying surrogate tissue
and tumor cell signaling by Western blotting. Evaluating tumor blood flow utilizing dynamic
contrast enhanced MRI.

II. To study any pharmacokinetic interactions between these two agents. III. To assess
preliminary anti-tumor activity of this combination.

OUTLINE: This is an open-label, multicenter, dose-escalation study of 17-N-allylamino
17-demethoxygeldanamycin (17-AAG).

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

Cohorts of 5-6 patients receive escalating doses of 17-AAG until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that which 2 of 6 patients
experience dose-limiting toxicity.

After completion of study therapy, patients are followed for 60 days.

Inclusion Criteria:

- 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

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- 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

- 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

- The use of concomitant medications that prolong or may prolong QTc are excluded

- Patients who have significant cardiac disease including heart failure that meet New
York Heart Association (NYHA) class III and IV definitions, history of myocardial
infarction within one year of study entry, uncontrolled dysrhythmias, or poorly
controlled angina are excluded

- Patients with a prior history of cardiac or pulmonary toxicity after receiving
anthracyclines such as doxorubicin, daunorubicin, mitoxantrone, bleomycin or BCNU

- Patients with a greater or equal to grade 2 pulmonary or cardiac symptoms prior to
study entry

- Patients who have a history of serious ventricular arrhythmia (VT or VF, >= 3 beats
in a row), QTc> 450 msec for men and 470 msec for women, or LVEF =< 40% by MUGA are

- Patients with a history of prior radiation that potentially included the heart in the
field (e.g., mantle)

- Patients with active ischemic heart disease within 12 months

- Patients with a history of uncontrolled dysrhythmias or requiring antiarrythmic
drugs; patients with congenital long QT syndrome

- Patients with left bundle branch block

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

42 days

Safety Issue:


Principal Investigator

Ulka Vaishampayan

Investigator Role:

Principal Investigator

Investigator Affiliation:

Barbara Ann Karmanos Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

March 2005

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • Neoplasms



Barbara Ann Karmanos Cancer Institute Detroit, Michigan  48201