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A Phase I Study of 17-N-Allylamino-17-Demethoxy Geldanamycin (17-AAG, NSC# 330507, IND# 57,966) in Combination With Docetaxel in Patients With Advanced Solid Tumors

Phase 1
18 Years
Not Enrolling
Recurrent Prostate Cancer, Stage IV Prostate Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

A Phase I Study of 17-N-Allylamino-17-Demethoxy Geldanamycin (17-AAG, NSC# 330507, IND# 57,966) in Combination With Docetaxel in Patients With Advanced Solid Tumors


I. Determine the maximum tolerated dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)
administered with docetaxel in patients with progressive metastatic prostate cancer or other
progressive metastatic or unresectable solid tumors.

II. Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin
(17-AAG). Patients are assigned to 1 of 2 treatment groups.

Group 1: Patients receive docetaxel IV over 1 hour and 17-AAG IV over 1-2 hours on day 1.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group 2: Patients receive docetaxel IV over 30 minutes and 17-AAG as in group 1. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients per group 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 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 20 additional patients (10
per group) are treated at the MTD.

Patients are followed every 2-3 months.

Inclusion Criteria:

- Histologically confirmed metastatic or unresectable malignancy for which standard
curative or palliative therapy does not exist or is no longer effective

- Progressive disease manifested by the following parameters

- For prostate cancer:

- Must have castrate, metastatic disease defined by disease progression
after surgical castration or treatment with a gonadotropin-releasing
hormone (GnRH) analog (testosterone level less than 50 ng/mL)

- Patients who have not undergone surgical orchiectomy should continue
on medical therapies to maintain castrate levels of testosterone

- Progressive metastatic disease on imaging studies (bone scan, CT scan, or
MRI) OR metastatic disease and a rising prostate-specific antigen (PSA)

- Biochemical progression indicated by at least 3 rising PSA values (obtained
at least 1 week apart) from a baseline OR 2 rising PSA values (more than 1
month apart), where the percentage increase over the range of values is at
least 25%

- Patients who have received an antiandrogen as part of first-line hormonal
therapy must have shown progression of disease off of the antiandrogen
prior to study enrollment

- For other solid tumors:

- Development of new lesions or an increase in pre-existing lesions by bone
scintigraphy, CT scan, MRI, positron emission tomography, or physical

- Patients whose sole criterion for progression is an increase in a
biochemical marker (e.g., carcinoembryonic antigen or CA 15-3) or an
increase in symptoms are not eligible

- Patients with metastatic disease must not be progressing to the extent as to require
palliative treatment within 4 weeks of study entry

- No active brain metastases

- Performance status - Karnofsky 70-100%

- More than 6 months

- WBC at least 3,000/mm^3

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT < 1.5 times ULN

- PT ≤ 1.1 times ULN

- Creatinine no greater than 1.4 mg/dL or within ULN

- Creatinine clearance greater than 55 mL/min

- No prior history of pulmonary toxicity after receiving anthracyclines (e.g.,
doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride,
bleomycin, or carmustine)

- No dyspnea ≥ grade 2 at rest on room air

- No requirement for supplementary oxygen therapy or oxygen saturations ≤ 88%

- No clinically significant pulmonary comorbidities that require medication (e.g.,
severe chronic obstructive pulmonary disease that could predispose patient to
pulmonary toxicity)

- QTc ≤ 450 msec for male patients (470 for female patients)

- LVEF > 40% by echocardiogram or MUGA

- Echocardiogram or MUGA required for patients with any of the following:

- Myocardial infarction > 1 year ago

- NYHA class I or II CHF

- Atrial fibrillation

- Right or left bundle branch block by EKG

- No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or
ventricular fibrillation ≥ 3 beats in a row)

- No myocardial infarction within the past year

- No active ischemic heart disease within the past year

- No New York Heart Association (NYHA) class III or IV congestive heart failure (CHF)

- No poorly controlled angina

- No uncontrolled dysrhythmia

- No congenital long QT syndrome

- No left bundle branch block

- No other significant cardiac disease

- No prior history of cardiac toxicity after receiving anthracyclines such as
doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride,
bleomycin, or carmustine

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No history of severe hypersensitivity reaction to paclitaxel, docetaxel, or
polysorbate 80

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study compliance

- No grade 2 or greater symptomatic peripheral neuropathy

- No allergy to eggs or egg products

- No other concurrent uncontrolled illness

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

- See Disease Characteristics

- At least 4 weeks since prior radiotherapy and recovered

- No concurrent radiotherapy to sole measurable lesion

- No prior mantle-field radiotherapy

- See Disease Characteristics

- No concurrent surgery for sole measurable lesion

- Recovered from prior therapy

- At least 1 week since prior ketoconazole and recovered

- At least 4 weeks since prior investigational anticancer therapeutic drugs

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent medications that prolong QTc interval

- No concurrent medication used to control arrhythmias

- Calcium blockers and beta blockers allowed

- No other concurrent investigational agents

- No other concurrent anticancer agents or therapies (investigational or commercial)

- No concurrent CYP3A4 inhibitors, including any of the following:

- Fluconazole

- Itraconazole

- Ketoconazole

- Macrolide antibiotics (azithromycin, clarithromycin, erythromycin, or

- Nifedipine

- Verapamil

- Diltiazem

- Cyclosporine

- Grapefruit juice

- No concurrent CYP3A4 inducers, including any of the following:

- Carbamazepine

- Phenobarbital

- Phenytoin

- Rifampin

- No concurrent herbal extracts or tinctures with CYP3A4 inhibitory activity, including
any of the following:

- Hydrastis canadensis (goldenseal)

- Hypericum perforatum (St. John's wort)

- Uncaria tomentosa (cat's claw)

- Echinacea angustifolia roots

- Trifolium pratense (wild cherry)

- Matricaria chamomilla (chamomile)

- Glycyrrhiza glabra (licorice)

- Dillapiol

- Hypericin

- Naringenin

- Concurrent CYP3A4 substrates allowed

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose determined by dose-limiting toxicities assessed using the NCI Common Toxicity Criteria (CTC) version 2.0

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

David Solit

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

February 2003

Completion Date:

Related Keywords:

  • Recurrent Prostate Cancer
  • Stage IV Prostate Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Prostatic Neoplasms
  • Neoplasms



Memorial Sloan-Kettering Cancer Center New York, New York  10021