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Radiation Therapy (IMRT) + RAD001 (Everolimus) + Cisplatin for Patients With Head and Neck Cancer

23 juli 2013 bijgewerkt door: Memorial Sloan Kettering Cancer Center

A Phase I Study of Radiation Therapy (IMRT) + RAD001 (Everolimus) + Cisplatin for Patients With Head and Neck Cancer

The purpose of this study is to determine the best doses of RAD001 (everolimus) tablets and cisplatin to give to patients who are receiving radiation therapy for head and neck cancer.

Studie Overzicht

Studietype

Ingrijpend

Inschrijving (Werkelijk)

13

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

    • New York
      • New York, New York, Verenigde Staten, 10065
        • 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

Inclusion Criteria:

  • Pathologically confirmed head and neck carcinoma, any histology (other than sarcoma, lymphoma, or melanoma). Patients with thyroid cancer (papillary, follicular, undifferentiated, Hurthle cell, medullary, or anaplastic) may be eligible.
  • Patients with cutaneous squamous cell cancer or basal cell cancer arising in the head and neck may be eligible.
  • Patients will have either Stage III- IVB unresected disease (Patients with stage II-IV B hypopharynx cancer and patients with Stage IIB - IVB nasopharynx cancer may also be eligible) OR
  • Will be status post macroscopically complete resection of disease with one of the following poor risk features in the surgical pathology specimen:

Malignant involvement of 2 or more regional lymph nodes Extracapsular extension of nodal disease Microscopically involved mucosal margins of resection T3 or T4 pathologic stage (excluding T3N0 laryngeal squamous cell cancer) Perineural involvement Oral cavity or oropharyngeal primaries with nodal disease at levels IV or V

  • Age > or = to 18 years
  • Karnofsky performance status > or = to 70%
  • Adequate bone marrow function: Absolute neutrophil count > than or = to 1.5 X 109/L, Platelets > or = to 100 x 109/L, Hemoglobin > 10 g/dL.
  • Adequate liver function: serum bilirubin < or = to 1.5 X upper limit of normal(ULN), and serum transaminases (alanine aminotransferase, ALT; aspartate aminotransferase, AST) activity < or = to 2.0 X ULN.
  • Adequate renal function: serum creatinine within institutional normal limits, or calculated creatinine clearance (by Cockcroft and Gault method) > or = to 45 mL/min for patients with creatinine limits above institutional normal.
  • INR < 1.5 or aPTT < 1.5 X upper limits of normal
  • For women of child-bearing potential, negative urine or serum pregnancy test within 14 days prior to administration of RAD001.
  • Men and women of childbearing potential must be willing to consent to using effective birth control methods while on treatment and for at least 3 months there after.
  • The planned radiation therapy treatment dose must meet protocol requirements (Resected tumors/post-operative patients: maximum planned dose 66 Gy. Unresected tumors: maximum planned dose 70 Gy).

Exclusion Criteria:

  • Any prior radiation therapy for head and neck cancer. Any prior radiation therapy to >25% of the bone marrow. Any prior radiation to whole pelvis and/or brain.
  • Patients with unresected squamous cell cancer (SCC) arising in the oral cavity, oropharynx, larynx, or hypopharynx are excluded, unless they at have received at least 2 cycles of induction chemotherapy with a regimen that includes cisplatin or carboplatin. (For patients with unresected head and neck tumors other than SCC of oral cavity, oropharynx, larynx, or hypopharynx, there is no requirement for induction chemotherapy prior to protocol chemoradiation)..
  • Therapeutic anticoagulation with coumadin (warfarin)
  • Peripheral neuropathy > or = to grade 3, according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.
  • Hypertriglyceridemia > or = to grade 2 (CTCAE version 3.0).
  • Patients who require chronic treatment with steroids ( > prednisone 5 mg/day) or other immunosuppressive agents are excluded. Both cisplatin and RAD001 are immunosuppressive, and chronic steroid use (> prednisone 5 mg/day) or use of other immunosuppressive agents might increase the risk of lethal infection in this setting. Patients on low- dose steroid replacement regimens (< or = to prednisone 5 mg/day) are not excluded, because low dose steroids should not be immunosuppressive.
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
  • Active infection or serious underlying medical condition that would impair the patient's ability to receive protocol treatment. Other concurrent severe and/or uncontrolled medical disease which would compromise participation in the study in the opinion of the investigator (e.g., uncontrolled diabetes, unstable angina, or congestive heart failure - New York Heart Association Class III or IV)
  • HIV-positive patients. These patients are at increased risk of lethal infections when treated with marrow suppressive therapy. Additionally, pharmacokinetic interactions between antiretroviral therapy and the study regimen may be problematic for these patients.
  • Women who are pregnant or lactating
  • Other active malignancy, other than indolent malignancies which the investigator determines are unlikely to interfere with treatment and safety analysis. For example, patients with nonmelanoma skin cancer, in situ carcinoma of the cervix, or prostate cancer with no current biochemical (PSA) or radiologic evidence of disease may enroll.
  • Impaired lung function: O2 saturation 88% or less at rest on room air by Pulse Oximetry. If O2 saturation is < or = to 88% at rest, further pulmonary function tests (PFTs) should be ordered to confirm normal pulmonary function and eligibility.
  • Patients should not receive immunization with attenuated live vaccines within one week of study entry or during the study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines.
  • Liver disease such as cirrhosis or severe hepatic impairment (Childs-Pugh class C).

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
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Chemoradiation
  • IMRT, 1 fraction/day, over approximately 33 treatment days
  • RAD001 per oral or PEG, per dose escalation scheme (Days 1 - 42)
  • Cisplatin IV weekly, per dose escalation scheme (Days 1, 8, 15, 22, 29, 36)

All patients will receive standard treatment with definitive radiation therapy (IMRT, intensity modulated radiation therapy), administered as one fraction per day (Monday through Friday) over approximately 33 fractions. Patients with resected tumors will be treated to a maximum dose of 66 Gy. Patients with unresected tumors will be treated to a maximum dose of 70 Gy.

Patients will receive daily RAD0001 it will be administered orally or via percutaneous gastrostomy tube (PEG) once daily according to the dose escalation scheme plus cisplatin intravenously once per week (Days 1, 8, 15, 22, 29, 36) according to the dose escalation scheme.

Approximately 3 - 4 months after completion of chemoradiation, radiologic response assessment will be performed. This will include cross-sectional imaging of the primary tumor (with CT scan and/or MRI) as well as a whole body FDG-PET (fluorodeoxyglucose positron emission tomography) scan.

All patients will receive standard treatment with definitive radiation therapy (IMRT, intensity modulated radiation therapy), administered as one fraction per day (Monday through Friday) over approximately 33 fractions. Patients with resected tumors will be treated to a maximum dose of 66 Gy. Patients with unresected tumors will be treated to a maximum dose of 70 Gy.

Patients will receive daily RAD0001 it will be administered orally or via percutaneous gastrostomy tube (PEG) once daily according to the dose escalation scheme plus cisplatin intravenously once per week (Days 1, 8, 15, 22, 29, 36) according to the dose escalation scheme.

Approximately 3 - 4 months after completion of chemoradiation, radiologic response assessment will be performed. This will include cross-sectional imaging of the primary tumor (with CT scan and/or MRI) as well as a whole body FDG-PET (fluorodeoxyglucose positron emission tomography) scan.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
To establish the phase II recommended dose of oral RAD001 (everolimus) tablets + weekly intravenous cisplatin given concurrently with radiation therapy.
Tijdsspanne: 3 months
3 months

Secundaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
To evaluate the safety and tolerability of oral RAD001 + radiation therapy + intravenous cisplatin.
Tijdsspanne: 3 months
3 months
To estimate the incidence of over-expression of eIF4E in surgical margins by immunohistochemistry (IHC).(only for those subjects who undergo primary surgery)
Tijdsspanne: 3 months
3 months
To describe the pharmacokinetics of RAD001 administered by PEG (percutaneous gastrostomy) tube.
Tijdsspanne: 3 months
3 months

Medewerkers en onderzoekers

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

Onderzoekers

  • Hoofdonderzoeker: Matthew Fury, MD,PhD, Memorial Sloan Kettering Cancer Center

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

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 maart 2009

Primaire voltooiing (Werkelijk)

1 juli 2013

Studie voltooiing (Werkelijk)

1 juli 2013

Studieregistratiedata

Eerst ingediend

6 maart 2009

Eerst ingediend dat voldeed aan de QC-criteria

6 maart 2009

Eerst geplaatst (Schatting)

10 maart 2009

Updates van studierecords

Laatste update geplaatst (Schatting)

25 juli 2013

Laatste update ingediend die voldeed aan QC-criteria

23 juli 2013

Laatst geverifieerd

1 juli 2013

Meer informatie

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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