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Gemcitabine Hydrochloride and Tanespimycin in Treating Patients With Recurrent Advanced Ovarian Epithelial or Peritoneal Cavity Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00093496
First received: October 6, 2004
Last updated: May 2, 2014
Last verified: October 2011
  Purpose

Phase II trial to study the effectiveness of gemcitabine hydrochloride and tanespimycin in treating patients who have recurrent advanced ovarian epithelial or primary peritoneal cavity cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and tanespimycin, work in different ways to stop tumor cells from dividing so they stop growing or die.


Condition Intervention Phase
Primary Peritoneal Cavity Cancer
Recurrent Ovarian Epithelial Cancer
Stage III Ovarian Epithelial Cancer
Stage IV Ovarian Epithelial Cancer
Drug: gemcitabine hydrochloride
Drug: tanespimycin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial Of Gemcitabine in Combination With 17-Allylaminogeldamycin (17-AAG) In Advanced Epithelial Ovarian And Primary Peritoneal Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of Patients Who Experience a Confirmed Response According to Modified RECIST Criteria. [ Time Frame: Participants were evaluated every 6 weeks on treatment, with median treatment length of 12 weeks (3 week minimum and 42 week maximum). ] [ Designated as safety issue: No ]

    Objective response will be measured using the modified RECIST criteria. A confirmed response requires an objective status of complete or partial response on 2 consecutive evaluations occurring 4 or more weeks apart.

    Complete Response (CR): Disappearance of all target lesions and normalization of tumor biomarkers.

    Partial Response (PR): At least a 30% decrease in the sum of the target lesions from the baseline.



Secondary Outcome Measures:
  • Times to Progression [ Time Frame: Participants were evaluated every 6 weeks on treatment (maximum 42 weeks), and followed up to 5 years from registration. ] [ Designated as safety issue: No ]
    Defined as the time from registration to the date of progression or last follow-up, whichever comes first. Estimated using the method of Kaplan-Meier

  • Overall Survival [ Time Frame: Every 3 months until disease progression and then every 6 months for up to 5 years. ] [ Designated as safety issue: No ]
    Defined as the time from registration to date of last follow-up or death due to any cause. Estimated using the method of Kaplan-Meier.

  • Toxicity [ Time Frame: Participants were evaluated every 6 weeks on treatment (maximum 42 weeks) ] [ Designated as safety issue: Yes ]
    Defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 as an adverse event classified as either possibly, probably, or definitely related to study treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.


Enrollment: 29
Study Start Date: October 2007
Study Completion Date: March 2012
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy)
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 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.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: tanespimycin
Given IV
Other Name: 17-AAG

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00093496

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Paul Haluska Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00093496     History of Changes
Obsolete Identifiers: NCT01646918, NCT01664312
Other Study ID Numbers: NCI-2009-00052, NCI-2009-00052, CDR0000388036, NCI-6307, MAYO-MC0362, MC0362, 6307, P30CA015083, N01CM62205
Study First Received: October 6, 2004
Results First Received: March 22, 2013
Last Updated: May 2, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Ovarian Diseases
Peritoneal Diseases
Urogenital Neoplasms
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014