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A Phase II Trial Of Gemcitabine in Combination With 17-Allylaminogeldamycin (17-AAG) In Advanced Epithelial Ovarian And Primary Peritoneal Carcinoma


Phase 2
18 Years
N/A
Not Enrolling
Female
Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer, Stage III Ovarian Epithelial Cancer, Stage IV Ovarian Epithelial Cancer

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Trial Information

A Phase II Trial Of Gemcitabine in Combination With 17-Allylaminogeldamycin (17-AAG) In Advanced Epithelial Ovarian And Primary Peritoneal Carcinoma


OBJECTIVES:

I. Determine the response rate, time to progression, and survival of patients with recurrent
advanced ovarian epithelial or primary peritoneal cavity cancer treated with gemcitabine
hydrochloride and 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) (tanespimycin).

II. Determine the toxicity of this regimen in these patients. III. Correlate the effect of
17-AAG alone on chaperone and client proteins in tumor samples and peripheral blood
mononuclear cells with response, time to progression, and survival of these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to gemcitabine
hydrochloride therapy (gemcitabine hydrochloride-naive/no prior exposure to gemcitabine
hydrochloride vs gemcitabine hydrochloride-resistant/prior exposure to gemcitabine
hydrochloride as a single agent with disease progression while on treatment). Patients
receive tanespimycin intravenously (IV) over 2 hours on days 1 and 8 during course 1 and
days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on
day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21
days in the absence of disease progression or unacceptable toxicity. Patients are followed
every 3 months until disease progression and then every 6 months for up to 5 years.


Inclusion Criteria:



- Diagnosis of ovarian epithelial or primary peritoneal cavity cancer

- Relapsed disease

- Persistent disease

- Platinum-resistant disease, defined as having evidence of disease that would be
expected to be non-responsive to additional platinum-containing regimens or
contraindication to platinum-based chemotherapy and 1 of the following:

- Failure to obtain a complete response to initial platinum therapy

- Recurrence < 6 months after completing a platinum-containing regimen for initial
or recurrent disease

- Any of the above situations and following treatment with additional chemotherapy
regimens (e.g., non-platinum containing regimens)

- Relative or absolute contraindication to platinum-based chemotherapy regimens
(e.g., platinum allergy) as determine by the investigator

- Measurable or evaluable disease

- Patients with a rising CA 125 level, even in the absence of other indicators of
disease, allowed provided CA 125 is ≥ 2 times upper limit of normal (ULN)

- Patients with accessible disease must be willing to undergo tumor biopsies

- No CNS metastases

- Performance status - ECOG 0-2

- WBC ≥ 3,000/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9.0 g/dL

- Bilirubin normal

- Alkaline phosphatase ≤ 2.5 times ULN

- AST ≤ 2.5 times ULN

- Creatinine ≤ 1.5 times ULN

- Ejection fraction > 40% by ECHO for patients with prior anthracycline therapy

- No significant cardiac disease including any of the following:

- New York Heart Association class III or IV heart disease

- History of myocardial infraction within the past year

- Uncontrolled dysrhythmias or requirement for antiarrhythmic drugs

- Poorly controlled angina

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

- No history of QTc ≥ 500 msec

- No active ischemic heart disease within the past 12 months

- No congenital long QT syndrome

- No left bundle branch block

- No cardiac symptoms ≥ grade 2

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

- Does not meet the medicare criteria for home oxygen

- No pulse oximetry at rest and exercise < 88%

- No symptomatic pulmonary disease requiring medication including any of the following:

- Dyspnea on or off exertion

- Paroxysmal nocturnal dyspnea

- Oxygen requirement

- Significant pulmonary disease (e.g., chronic obstructive/restrictive pulmonary
disease)

- No pulmonary symptoms ≥ grade 2

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

- K+, Mg ++, and Ca ++ normal

- No seizure disorder

- No uncontrolled infection

- No history of serious allergic reaction to eggs

- More than 4 weeks since prior immunotherapy

- More than 4 weeks since prior biologic therapy

- No concurrent immunotherapy

- No concurrent routine or prophylactic colony-stimulating factors (e.g., filgrastim
[G-CSF] or sargramostim [GM-CSF])

- See Disease Characteristics

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

- Prior gemcitabine hydrochloride allowed provided 1 of the following criteria is met:

- Patients have no prior exposure to gemcitabine hydrochloride

- Patients who have prior exposure to gemcitabine hydrochloride as a single agent
have experienced progressive disease while on treatment

- No other concurrent chemotherapy

- No prior radiotherapy to > 25% of bone marrow

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

- Chest wall irradiation or other radiotherapy techniques that do not include the
heart in the radiation field area allowed

- More than 4 weeks since prior radiotherapy

- More than 4 weeks since prior radiopharmaceuticals

- No concurrent radiotherapy

- No other concurrent investigational therapy

- No concurrent medications that may prolong QTc

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Proportion of patients who experience a confirmed response according to modified RECIST criteria

Outcome Description:

Estimated by the standard binomial estimator, i.e., the number of successes divided by the total number of evaluable patients, and binomial confidence intervals for 2-stage designs calculated according to the approach of Duffy and Santner. 95% confidence interval will be calculated.

Outcome Time Frame:

Every 6 weeks

Safety Issue:

No

Principal Investigator

Paul Haluska

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00052

NCT ID:

NCT00093496

Start Date:

July 2004

Completion Date:

Related Keywords:

  • Primary Peritoneal Cavity Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Stage III Ovarian Epithelial Cancer
  • Stage IV Ovarian Epithelial Cancer
  • Peritoneal Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms

Name

Location

Mayo ClinicRochester, Minnesota  55905