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Sirolimus and Cetuximab in Advanced Malignancies

16. november 2015 oppdatert av: M.D. Anderson Cancer Center

A Phase I Trial of Sirolimus and Cetuximab in Patients With Advanced Malignancies

The goal of this clinical research study is to find the highest tolerable dose of the combination of sirolimus and cetuximab that can be given to patients with advanced cancer. The safety of this drug combination will also be studied.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

The Study Drugs:

Cetuximab is designed to prevent or slow down the growth of cancer cells by blocking protein on the surface of the cancer cell, called the epidermal growth factor receptor (EGFR).

Sirolimus is designed to block a protein called mTOR inside the cancer cell. This may interfere with the growth or spread of cancer cells or possibly kill the cancer cells.

Study Drug Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of cetuximab and sirolimus based on when you joined this study. Up to 9 dose levels of cetuximab and sirolimus will be tested. Three (3) to 9 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the combination of cetuximab and sirolimus is found.

Once the highest tolerated dose of the combination of cetuximab and sirolimus is found, 2 groups of additional participants (Group 1 and Group 2, each of 14 participants) will be enrolled and receive the study drugs at that dose level. Another 14 participants with the non-small lung and head and neck cancer will receive the study drug at that dose level, as well.

Study Drug Administration:

Each study "cycle" is 28 days.

Everyday, you will take sirolimus by mouth 1 time a day. You should take it at about the same time each day with food and a cup of water.

On Days 1, 8, 15, and 22 of each cycle, you will receive cetuximab by vein over 2 hours. If the first dose is well tolerated, you will receive the next dose over 1 hour.

Study Visits:

At every study visit, you will be asked about any current health conditions you have, drugs you are taking, and if you have experienced any side effects.

Between Days 8 and 15 of Cycle 1, the following tests and procedures will be performed:

-If you are enrolled in a Group 2 of the highest drug combination dose, you will have a tumor biopsy and your blood (about 1-3 tablespoons) will be drawn for pharmacodynamic (PD) testing.

About Days 8 and 22 of Cycle 1, the following tests and procedures will be performed:

  • You will have a physical exam.
  • Blood (about 2 teaspoons) will be drawn for routine tests.

About Day 15 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests.

About Day 22 of Cycles 2 and then every 1-2 cycles, the following tests and procedures will be performed:

  • You will have a physical exam.
  • Blood (about 2 teaspoons) will be drawn for routine tests.

Every 4 weeks, you will have a blood (about 1 teaspoon) drawn or urine collected for pregnancy test if you are able to become pregnant.

Every 8 weeks, you will have an x-ray, CT scan, MRI, and/or PET/CT to check the status of the disease. The study doctor thinks it is needed, they will be performed more often.

Length of Study:

You may stay on study for as long as you are benefitting. You will be taken off study if you experience intolerable side effects, the study doctor thinks it is in your best interest, or the cancer gets worse.

End-of-Study Visit:

About 28 days after the last dose of study drugs, you will have an end-of-study visit. At this visit, the following tests or procedures may be performed:

  • You will have a physical exam, including measurement of your vital signs.
  • Your performance status will be recorded.
  • Blood (about 2 teaspoons) will be drawn for routine tests.
  • If the doctor thinks it is needed, you will have an x-ray, CT, MRI, and/or PET/CT to check the status of the disease.

This is an investigational study. Sirolimus is FDA approved and commercially available as an anti-rejection drug for kidney transplant recipients. Cetuximab is FDA approved and commercially available for the treatment of colorectal and head/neck cancers. The combination of these drugs is investigational.

Up to 137 patients will take part in this study. All will be enrolled at MD Anderson.

Studietype

Intervensjonell

Registrering (Faktiske)

165

Fase

  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Forente stater
    • Texas
      • Houston, Texas, Forente stater, 77030
        • UT MD Anderson Cancer Center

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  1. Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months.
  2. Patients must be >/= 3 weeks beyond treatment with a cytotoxic chemotherapy regimen, or therapeutic radiation, or major surgery. Patients may have received palliative localized radiation immediately before or during treatment providing radiation is not delivered to the only site of disease being treated under this protocol. For biologic/targeted agents patients must be >/= 5 half-lives or >/= 3 weeks form the last dose (whichever comes first).
  3. Eastern Cooperative Oncology Group (ECOG) performance status </= 3.
  4. Patients must have normal organ and marrow function defined as: absolute neutrophil count >/= 1,000/mL; platelets >/=50,000/mL; creatinine </= 3 X upper limit of normal (ULN); total bilirubin </= 2.0; ALT(SGPT) </= 5 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; ALT(SGPT) </= 8 X ULN; cholesterol </= 350 mg/dL; triglycerides </= 400 mg/dL.
  5. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose.
  6. Patients with colorectal cancer with Kirsten rat sarcoma (kRAS) mutations (mutational status must be available prior to entering the study)
  7. Patients must be able to understand and be willing to sign a written informed consent document.

Exclusion Criteria:

  1. Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
  2. Pregnant or lactating women.
  3. History of hypersensitivity to cetuximab, murine products, or any component of the formulation.
  4. History of hypersensitivity to sirolimus.
  5. History of hypersensitivity to any component of the formulation.
  6. Patients with colorectal cancer with kRAS mutations. (mutational status must be available prior to entering the study)
  7. Patients unwilling or unable to sign informed consent document.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Sirolimus + Cetuximab
Sirolimus beginning dose 3 mg by mouth on Day 1, and 1 mg on Days 2 - 28 for a 28 day cycle. Cetuximab Beginning dose 100 mg/m^2 by vein over two hours on Day 1, and 65 mg/m^2 on Days 8, 15 and 22 for a 28 day cycle.
Legemiddel: Sirolimus
Beginning dose 3 mg by mouth on Day 1, and 1 mg on Days 2 - 28 for a 28 day cycle.
Andre navn:
  • Rapamune
Legemiddel: Cetuximab
Beginning dose 100 mg/m^2 by vein over two hours on Day 1, and 65 mg/m^2 on Days 8, 15 and 22 for a 28 day cycle.
Andre navn:
  • C225
  • Erbitux
  • IMC-225

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicities (DLT) of Combination Treatment with Sirolimus and Cetuximab
Tidsramme: 4 weeks
MTD defined by DLTs that occur in the first cycle (4 weeks). DLT defined as any clinically grade 3 or 4 non-hematologic toxicity as defined in the NCI CTC v3.0, expected and believed to be related to the study medications (except nausea and vomiting, electrolyte imbalances responsive to appropriate regimens or alopecia), any grade 4 hematologic toxicity lasting at least 3 weeks or longer (as defined by the NCI-CTC v3.0) or associated with bleeding and/or sepsis; any grade 4 nausea or vomiting > 5 days despite maximum anti-nausea regimens, and any other grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in the NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 that is attributable to therapy.
4 weeks

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

M.D. Anderson Cancer Center

Etterforskere

  • Hovedetterforsker: Filip Janku, MD,PHD, UT MD Anderson Cancer Center

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Hjelpsomme linker

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. juli 2009

Primær fullføring (Faktiske)

1. mai 2014

Studiet fullført (Faktiske)

1. mai 2014

Datoer for studieregistrering

Først innsendt

14. juli 2009

Først innsendt som oppfylte QC-kriteriene

14. juli 2009

Først lagt ut (Anslag)

16. juli 2009

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

18. november 2015

Siste oppdatering sendt inn som oppfylte QC-kriteriene

16. november 2015

Sist bekreftet

1. mai 2014

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 2009-0226
  • NCI-2012-01271 (Registeridentifikator: NCI CTRP)

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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