Chemotherapy in Treating Patients With Refractory Advanced Solid Tumors or Hematologic Cancer
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.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Undersøgelsestype
Fase
Fase
- Fase 1
Kontakter og lokationer
Studiesteder
-
-
California
-
Los Angeles, California, Forenede Stater, 90095
- Jonsson Comprehensive Cancer Center, UCLA
-
-
New York
-
New York, New York, Forenede Stater, 10021
- Memorial Sloan-Kettering Cancer Center
-
-
Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Samarbejdspartnere
Samarbejdspartnere
Datoer for undersøgelser
Studer store datoer
Studiestart
Studiestart
Primær færdiggørelse (Faktiske)
Primær færdiggørelse
Studieafslutning (Faktiske)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
- stadium IV nyrecellekræft
- tilbagevendende nyrecellekræft
- stadium IV brystkræft
- stadium IIIA brystkræft
- tilbagevendende brystkræft
- stadium IIIB brystkræft
- tilbagevendende ikke-småcellet lungekræft
- stadium III blærekræft
- tilbagevendende blærekræft
- stadium IV blærekræft
- stadium III prostatacancer
- stadium IV prostatacancer
- tilbagevendende prostatakræft
- fase IIIA ikke-småcellet lungekræft
- stadium IIIB ikke-småcellet lungekræft
- fase IV ikke-småcellet lungekræft
- uspecificeret voksen solid tumor, protokol specifik
- ubehandlet metastatisk planehalskræft med okkult primær
- tilbagevendende metastatisk planehalskræft med okkult primær
- stadium III planocellulært karcinom i læben og mundhulen
- stadium III basalcellekarcinom i læben
- stadium III verrucous carcinom i mundhulen
- stadium III mucoepidermoid karcinom i mundhulen
- stadium III adenoid cystisk carcinom i mundhulen
- stadium IV planocellulært karcinom i læben og mundhulen
- stadium IV basalcellekarcinom i læben
- stadium IV verrucous carcinom i mundhulen
- stadium IV mucoepidermoid karcinom i mundhulen
- stadium IV adenoid cystisk carcinom i mundhulen
- tilbagevendende pladecellekarcinom i læben og mundhulen
- tilbagevendende basalcellekarcinom i læben
- tilbagevendende verrucous carcinom i mundhulen
- tilbagevendende mucoepidermoid karcinom i mundhulen
- tilbagevendende adenoid cystisk carcinom i mundhulen
- stadium III planocellulært karcinom i oropharynx
- stadium III lymfepitheliom i oropharynx
- stadium IV planocellulært karcinom i oropharynx
- stadium IV lymfepitheliom i oropharynx
- tilbagevendende pladecellekarcinom i oropharynx
- tilbagevendende lymfepitheliom i oropharynx
- stadium III planocellulært karcinom i nasopharynx
- stadium III lymfepitheliom i nasopharynx
- stadium IV planocellulært karcinom i nasopharynx
- stadium IV lymfepitheliom i nasopharynx
- tilbagevendende pladecellekarcinom i nasopharynx
- tilbagevendende lymfepitheliom i nasopharynx
- stadium III planocellulært karcinom i hypopharynx
- stadium IV planocellulært karcinom i hypopharynx
- tilbagevendende pladecellekarcinom i hypopharynx
- stadium III planocellulært karcinom i strubehovedet
- stadium III verrucous carcinom i strubehovedet
- stadium IV planocellulært karcinom i strubehovedet
- stadium IV verrucous carcinom i strubehovedet
- tilbagevendende pladecellekarcinom i strubehovedet
- tilbagevendende verrucous carcinom i strubehovedet
- stadium III planocellulært karcinom i paranasale sinus og næsehulen
- stadium III midtlinje letalt granulom i paranasal sinus og næsehulen
- stadium III esthesioneuroblastoma i paranasale sinus og næsehulen
- stadium IV planocellulært karcinom i paranasale sinus og næsehulen
- stadium IV midtlinje letalt granulom i paranasal sinus og næsehulen
- stadium IV esthesioneuroblastoma i paranasal sinus og næsehulen
- tilbagevendende pladecellekarcinom i paranasale sinus og næsehulen
- tilbagevendende middellinje letalt granulom i paranasale sinus og næsehulen
- tilbagevendende esthesioneuroblastom i paranasale sinus og næsehulen
- tilbagevendende spytkirtelkræft
- stadium III spytkirtelkræft
- stadium IV spytkirtelkræft
- stadium IV tyktarmskræft
- tilbagevendende tyktarmskræft
- stadium III ovarieepitelkræft
- stadium IV ovarieepitelkræft
- tilbagevendende ovarieepitelkræft
- stadium III tyktarmskræft
- stadium IIIC brystkræft
- tilbagevendende melanom
- stadium IV melanom
- kronisk fase kronisk myelogen leukæmi
- blastisk fase kronisk myelogen leukæmi
- recidiverende kronisk myelogen leukæmi
- stadium IV gastrisk cancer
- tilbagevendende mavekræft
- stadium III nyrecellekræft
- stadium III melanom
- stadium III mavekræft
- tilbagevendende akut lymfatisk leukæmi hos voksne
- ovariesarkom
- accelereret fase kronisk myelogen leukæmi
- borderline ovarieoverflade epitel-stromal tumor
- ovariestromal cancer
- tilbagevendende ovarie-kimcelletumor
- stadium III ovarie-kimcelletumor
- stadium IV ovarie-kimcelletumor
- tilbagevendende omvendt papilloma i paranasale sinus og næsehulen
- stadium III inverteret papilloma i paranasal sinus og næsehulen
- stadium IV inverteret papilloma i paranasale sinus og næsehulen
Yderligere relevante MeSH-vilkår
- Sygdomme i fordøjelsessystemet
- Hudsygdomme
- Luftvejssygdomme
- Neoplasmer efter histologisk type
- Neoplasmer
- Lungesygdomme
- Urologiske neoplasmer
- Urogenitale neoplasmer
- Neoplasmer efter sted
- Urologiske sygdomme
- Urinblæresygdomme
- Gastrointestinale neoplasmer
- Neoplasmer i fordøjelsessystemet
- Gastrointestinale sygdomme
- Mavesygdomme
- Genitale neoplasmer, mandlige
- Brystsygdomme
- Prostatasygdomme
- Neoplasmer i luftvejene
- Thoracale neoplasmer
- Neuroektodermale tumorer
- Neoplasmer, kimceller og embryonale
- Neoplasmer, nervevæv
- Neuroendokrine tumorer
- Nevi og melanomer
- Neoplasmer i maven
- Brystneoplasmer
- Neoplasmer i hoved og hals
- Prostatiske neoplasmer
- Lungeneoplasmer
- Leukæmi
- Urinblære neoplasmer
- Melanom
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- 99-037
- CDR0000067267 (Registry Identifier: PDQ (Physician Data Query))
- NCI-T99-0035
- UCLA-0206019
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