Phase I Study of 17- Allylamino-17 Demethoxygeldanamycin (17-AAG) in Combination With Paclitaxel in Advanced Solid Malignancies


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase I Study of 17- Allylamino-17 Demethoxygeldanamycin (17-AAG) in Combination With Paclitaxel in Advanced Solid Malignancies


OBJECTIVES:

I. Determine the maximum tolerated dose and recommended phase II dose of
17-N-allylamino-17-demethoxygeldanamycin (17-AAG) when administered with paclitaxel in
patients with metastatic or unresectable solid malignancy.

II. Determine the dose-limiting and non-dose-limiting toxic effects of this regimen in these
patients.

III. Determine the pharmacokinetics of this regimen in these patients. IV. Determine tumor
response in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of
17-N-allylamino-17-demethoxygeldanamycin (17-AAG). Patients receive 17-AAG IV over 1 hour
on days 1*, 4, 8, 11, 15 and 18 and paclitaxel IV over 1 hour on days 1, 8, and 15.
Treatment repeats every 28 days for 6 courses in the absence of disease progression or
unacceptable toxicity.

NOTE: *17-AAG is not administered on day 1 of course 1. 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 3 or 2 of 6 patients experience
dose-limiting toxicity. Once the MTD is determined, 6-12 patients are treated at the
recommended phase II dose.


Inclusion Criteria:



- Histologically confirmed solid malignancy

- Metastatic or unresectable disease

- Not amenable to standard curative or palliative therapy

- No known brain metastases

- Performance status - ECOG 0-2

- More than 12 weeks

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- WBC ≥ 3,000/mm^3

- AST and ALT ≤ 2.5 times upper limit of normal

- Bilirubin normal

- Creatinine normal

- Creatinine clearance ≥ 60 mL/min

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

- LVEF > 40% by MUGA

- 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 New York Heart Association class III or IV congestive heart failure

- No poorly controlled angina

- No history of uncontrolled dysrhythmia or requirement for antiarrhythmic drugs

- No history of congenital long QT syndrome

- No active ischemic heart disease within the past year

- No left bundle branch block

- No other significant cardiac disease

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective double barrier contraception for at least 1 week
before, during, and for at least 2 weeks after study participation

- No prior allergy to eggs

- No prior allergic reaction to compounds of similar chemical or biologic composition
to 17-AAG or paclitaxel

- No peripheral neuropathy > grade 1

- No concurrent uncontrolled illness

- No active or ongoing infection

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

- No concurrent granulocyte colony-stimulating factors

- Prior paclitaxel allowed

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered

- No prior 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)

- More than 4 weeks since prior radiotherapy

- No prior radiotherapy that included the heart in the field (e.g., mantle
radiotherapy)

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent therapeutic-dose warfarin for anticoagulation

- No concurrent medications that may prolong QTc interval

- No other concurrent investigational agents

- No other concurrent anticancer agents or therapies

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Phase 2 recommended doses of tanespimycin

Outcome Description:

Tabulated according to the NCI CTC.

Outcome Time Frame:

28 days

Safety Issue:

Yes

Principal Investigator

Suresh Ramalingam

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pennsylvania Medical Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02610

NCT ID:

NCT00087217

Start Date:

May 2004

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific

Name

Location
University of Pennsylvania Medical Center Philadelphia, Pennsylvania  19104