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Chemotherapy in Treating Patients With Refractory Advanced Solid Tumors or Hematologic Cancer

20 juni 2013 bijgewerkt door: Memorial Sloan Kettering Cancer Center

A Phase I Trial of 17-N-Allylamino-17-Demethoxy Geldanamycin (17-AAG, NSC #330507) Daily X 5 in Patients With Advanced Cancer Therapeutic Protocol

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin in treating patients with refractory advanced solid tumors or hematologic cancers.

Studie Overzicht

Gedetailleerde beschrijving

OBJECTIVES:

  • Determine the maximum tolerated dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) in patients with refractory or advanced solid tumors or hematologic malignancies.
  • Evaluate the effects of this drug on the expression of signaling proteins present on an individual patient's cancer at the start of treatment and, if possible, post treatment.

OUTLINE: This is a two-phase, dose-escalation, multicenter study. Patients are stratified according to disease (chronic myelogenous leukemia [CML] or Philadelphia chromosome [Ph]+ acute lymphoblastic leukemia [ALL] vs solid tumor).

Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 60-90 minutes twice weekly. Courses repeat every 12 weeks in the absence of disease progression (after at least 2 courses for CML or Ph+ ALL patients) or unacceptable toxicity.

  • Accelerated phase: Single patients receive escalating dose levels of 17-AAG until one patient experiences a first course grade 3 or greater toxicity or two different patients experience grade 2 toxicity during any course.
  • Standard phase: Cohorts of 3-6 patients in each stratum 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.

PROJECTED ACCRUAL: Approximately 51 patients will be accrued for this study.

Studietype

Ingrijpend

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

    • California
      • Los Angeles, California, Verenigde Staten, 90095
        • Jonsson Comprehensive Cancer Center, UCLA
    • New York
      • New York, New York, Verenigde Staten, 10021
        • Memorial Sloan-Kettering Cancer Center

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:

    • Histologically confirmed advanced primary or malignant solid tumor refractory to standard therapy or for which no curative standard therapy exists

      • Progressive disease evidenced by 1 of the following:

        • Non-prostate cancer (including, but not limited to, breast, ovary, head and neck, non-small cell lung, bladder, kidney, colon, stomach, or malignant melanoma)

          • Development of new lesions or an increase in existing lesions
          • No increase in a biochemical marker (e.g., carcinoembryonic antigen, CA-15-3, or an increase in symptoms) as sole measure of disease
    • Prostate cancer (androgen independent) meeting the following criteria:

      • Progressing metastatic disease on bone scan, CT scan, or MRI
      • Metastatic disease and rising prostate-specific antigen (PSA) values meeting 1 of the following criteria:

        • At least 3 rising PSA values obtained at least 1 week apart = 2 rising values more than 1 month apart with at least 25% increase over the range of values
      • Serum testosterone less than 30 ng/mL
      • Castrate status should be maintained by medical therapies if orchiectomy has not been performed
      • Progressive disease must be evident off antiandrogen therapy if received prior to study entry
      • Registered to protocol MSKCC-9040
    • Cytologically confirmed chronic, accelerated, or blastic phase chronic myelogenous leukemia (CML) or Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) refractory to standard therapy or for which no curative therapy exists

      • Progressive disease evidenced by 1 of the following:

        • Accelerated or blastic phase disease that is not responsive to standard therapy or loss of hematologic response to imatinib mesylate while remaining in chronic phase for CML
        • Relapsed or refractory after treatment with standard chemotherapy and imatinib mesylate for Ph-positive ALL
  • No active CNS or epidural tumor
  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Sex:

  • Not specified

Menopausal status:

  • Not specified

Performance status:

  • Karnofsky 70-100%

Life expectancy:

  • At least 6 months

Hematopoietic:

  • WBC greater than 3,500/mm^3
  • Platelet count greater than 100,000/mm^3
  • No restrictions based on peripheral blood counts for CML and Ph-positive ALL

Hepatic:

  • Bilirubin no greater than 1.2 times upper limit of normal (ULN)
  • AST less than 1.5 times ULN
  • Prothrombin time normal

Renal:

  • Creatinine no greater than 1.5 times ULN OR
  • Creatinine clearance greater than 60 mL/min

Cardiovascular:

  • No myocardial infarction within the past 6 months
  • Ejection fraction greater than 45% by radionuclide cardiac angiography
  • No ventricular aneurysm or other abnormal wall motion
  • No reversible defect by thallium stress test if any of the following conditions are present:

    • Ejection fraction less than 45% on radionuclide angiocardiography
    • Worrisome but nonexclusive cardiovascular history
    • Abnormal echocardiogram
  • Patients with the following history or clinical findings require additional diagnostic testing:

    • Significant Q waves (greater than 3 mm or greater than one-third of the height of the QRS complex)
    • ST elevation or depressions of greater than 2 mm that are not attributable to hypertension strain
    • Absence of regular sinus rhythm
    • Bundle branch block
    • Requirement for diuretics for reasons other than hypertension or digoxin for reasons other than atrial fibrillation
    • Prior mild to moderate congestive heart failure
  • No New York Heart Association class III or IV heart disease
  • No angina pectoris
  • No uncontrolled hypertension or intermittent claudication
  • No severe debilitating valvular disease

Pulmonary:

  • No severe debilitating pulmonary disease

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active infection requiring IV antibiotics
  • No symptomatic peripheral neuropathy grade 2 or higher
  • No other severe medical conditions that would increase risk for toxicity
  • No allergy to eggs or egg products

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 4 weeks since prior biologic therapy (including interferon for CML) and recovered

Chemotherapy:

  • At least 4 weeks since prior chemotherapy (3 days for hydroxyurea for CML or ALL) and recovered
  • No other concurrent chemotherapy

Endocrine therapy:

  • See Disease Characteristics
  • At least 4 weeks since prior endocrine therapy and recovered

Radiotherapy:

  • At least 4 weeks since prior radiotherapy and recovered
  • Concurrent radiotherapy to localized disease sites not being used to evaluate antitumor response allowed
  • No concurrent radiotherapy to only measurable lesion

Surgery:

  • See Disease Characteristics
  • Prior orchiectomy allowed
  • No concurrent surgery

Other:

  • At least 3 days since prior imatinib mesylate for CML or ALL
  • At least 4 weeks since prior investigational anticancer drugs and recovered
  • At least 4 weeks since prior palliative treatment for metastatic disease
  • No concurrent ketoconazole, warfarin, verapamil, miconazole, or erythromycin
  • No other concurrent investigational drugs

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 juli 1999

Primaire voltooiing (Werkelijk)

1 maart 2005

Studie voltooiing (Werkelijk)

1 maart 2005

Studieregistratiedata

Eerst ingediend

10 december 1999

Eerst ingediend dat voldeed aan de QC-criteria

26 januari 2003

Eerst geplaatst (Schatting)

27 januari 2003

Updates van studierecords

Laatste update geplaatst (Schatting)

24 juni 2013

Laatste update ingediend die voldeed aan QC-criteria

20 juni 2013

Laatst geverifieerd

1 juni 2013

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Andere studie-ID-nummers

  • 99-037
  • CDR0000067267 (Register-ID: PDQ (Physician Data Query))
  • NCI-T99-0035
  • UCLA-0206019

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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