17-AAG and Irinotecan in Treating Patients With Locally Advanced or Metastatic Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00119236
First received: July 12, 2005
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

This phase I trial is studying the side effects and best dose of 17-AAG and irinotecan in treating patients with locally advanced or metastatic solid tumors. Drugs used in chemotherapy, such as 17-AAG and irinotecan, work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: tanespimycin
Drug: irinotecan hydrochloride
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Labeled Non-Randomized Phase I Study of 17-N-allylamino-17-demethoxy Geldanamycin (17AAG) Administered With Irinotecan (CPT-11) in Patients With Advanced Solid Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose determined by dose-limiting toxicities [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Enrollment: 48
Study Start Date: May 2005
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive irinotecan IV over 30 minutes followed by 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)* IV over 2 hours on days 1 and 8. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable or improved disease after course 2 may receive additional courses of treatment.
Drug: tanespimycin
Other Name: 17-AAG
Drug: irinotecan hydrochloride
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of combined 17AAG and irinotecan given weekly for two weeks in a 21-day cycle that can be used for future phase II studies.

SECONDARY OBJECTIVES:

I. To explore the effects of the combination on the expression of Hsp90 client proteins in peripheral mononuclear cells and tumor tissues. Tumor biopsies will be performed before and after 17AAG treatment in 12 patients at the MTD ("Expanded Cohort") only.

II. To investigate the clinical pharmacokinetics of intravenous 17AAG, irinotecan, and their metabolites, in this combination.

III. To obtain preliminary data on the therapeutic activity of 17AAG in combination with irinotecan in patients with advanced solid tumors.

IV. To obtain preliminary result in the relationship between tumor response and p53-status.

OUTLINE: This is an open-label, non-randomized, dose-escalation study.

Patients receive irinotecan IV over 30 minutes followed by 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)* IV over 2 hours on days 1 and 8. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable or improved disease after course 2 may receive additional courses of treatment.

NOTE: *17-AAG is administered on days 2 and 8 during course 2 for patients treated at non-maximum tolerated doses (MTD) (dose-escalation portion) and on day 8 only during course 1 for patients treated at the MTD (expanded cohort).Cohorts of 3-6 patients receive escalating doses of 17-AAG and irinotecan until the 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. An additional 12 patients are treated at the MTD.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed solid tumor, excluding primary CNS tumors

    • Locally advanced or metastatic disease that is refractory to standard therapy OR for which no standard therapy exists
  • Tumor assessible for biopsy by Tru-cut^®, CT guidance, or endoscopy (for patients treated at the maximum tolerated dose [expanded cohort only])

    • Pleural effusions or abdominal ascites are not considered biopsy-accessible tissue
  • No known new CNS metastases that have not been previously treated
  • Performance status - Karnofsky 60-100%
  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin ≤ 1.5 mg/dL
  • AST and ALT ≤ 3 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
  • Creatinine ≤ 1.5 mg/dL
  • No history of cardiac arrhythmias
  • No myocardial infarction within the past 12 months
  • No active ischemic heart disease within the past 12 months
  • No New York Heart Association class III-IV congestive heart failure or LVEF < 40% by MUGA
  • No history of uncontrolled cardiac dysrhythmia or dysrhthmias requiring medication
  • No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
  • No congenital long QT syndrome
  • No left bundle branch block
  • QTc < 450 msec (for male patients)
  • QTc < 470 msec (for female patients)
  • Not pregnant
  • No nursing during and for 2 months after study participation
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 2 months after study participation
  • No serious or uncontrolled infection
  • No history of serious allergic reaction to eggs or egg products
  • No other medical condition that would preclude study participation
  • At least 3 weeks since prior immunotherapy
  • No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
  • At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • Prior irinotecan allowed
  • No prior 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)
  • At least 2 weeks since prior non-myelosuppressive chemotherapy (at the discretion of the principal investigator)
  • At least 3 weeks since prior radiotherapy
  • No prior radiotherapy field that included the heart (e.g., mantle)
  • Recovered from all prior therapy
  • At least 3 weeks since prior anticancer investigational therapeutic drugs
  • More than 7 days since prior and no concurrent inducers, inhibitors, or modifiers of CYP3A4, including any of the following:

    • Fluconazole
    • Itraconazole
    • Ketoconazole
    • Azithromycin
    • Clarithromycin
    • Erythromycin
    • Troleandomycin
    • Nifedipine
    • Verapamil
    • Diltiazem
    • Nefazodone
    • Cyclosporine
    • Grapefruit juice (> 1 quart/day)
    • Indinavir
    • Nelfinavir
    • Ritonavir
    • Saquinavir
    • Carbamazepine
    • Phenobarbital
    • Phenytoin
    • Rifampin
    • Hydrastis canadensis (goldenseal)
    • Hypericum perforatum (St. John's wort)
    • Uncaria tomentosa (cat's claw)
    • Echinacea angustifolia root
    • Trifolium pratense (wild cherry)
    • Matricaria chamomila (chamomile)
    • Glycyrrhiza glabra (licorice)
    • Dillapiol
    • Hypericin
    • Naringenin
  • No concurrent medications that would prolong QTc
  • No concurrent vitamins, antioxidants, herbal preparations, or supplements

    • Concurrent single daily multivitamin allowed
  • No other concurrent anticancer therapy
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational medications
  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: NCT00119236

Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Investigators
Principal Investigator: Archie Tse Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00119236     History of Changes
Other Study ID Numbers: NCI-2012-01467, 05-017, MSKCC-IRB-05017, NCI-7009, CDR0000434501, U01CA069856
Study First Received: July 12, 2005
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Irinotecan
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014