Lapatinib and Cetuximab in Patients With Solid Tumors (TYKERB-ITUX 1)
A Phase I Study of Lapatinib and Cetuximab in Patients With Solid Tumors
This trial is for patients with colon cancer, head and neck cancer and lung cancer that has not responded to standard therapy.
Cetuximab targets a receptor on cancer cells called the Epidermal Growth Factor Receptor or EGFR. It is thought that this receptor is turned "on" in some cancers, enabling cancer cells to divide and grow. Blocking this receptor can turn this signal off. Cetuximab blocks this receptor from the outside of cancer cells. It is thought that cancer cells can turn this signal back on by the EGFR joining with a related receptor called ErbB2. Lapatinib blocks both EGFR and ErbB2 from the inside of cancer cells. In laboratory experiments it has been found that combining drugs that target both EGFR and ErbB2 might work better in turning this signal back off. The purpose of this study is to determine the maximum dosages that patients can tolerate when these two medicines are given at the same time.
In addition, in order to be on this trial, patients must agree to have a tumor biopsy before starting treatment on this study and 21 days after starting treatment. These biopsies are a required part of the study. Patients must also agree to have blood drawn for research testing to see whether genetic differences between patients explain different reactions to and side effects from, these medicines.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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District of Columbia
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Washington, District of Columbia, Verenigde Staten, 20007
- Georgetown University Medical Center
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- At least one measurable lesion by RECIST criteria
- A tumor lesion that can be readily biopsied using a core needle via clinical exam, ultrasound, CT, or fluoroscopic-guidance
- Over the age of 18 years and able to provide informed consent
- Patients must have progressed after standard therapy for metastatic/ recurrent disease including 5-FU containing regimens for patients with colorectal cancer, and platinum-containing regimens for patients with head and neck cancer and non-small cell lung cancer.
- Patients may have received cetuximab, panitumumab or erlotinib previously
- Adequate kidney, liver, and bone marrow function
- Life expectancy greater than 3 months
- ECOG performance status </= 2
- Normal left ventricular ejection fractions
Exclusion Criteria:
- Chemotherapy or surgery within 4 weeks prior to treatment start
- Radiation treatment within 3 weeks prior to treatment start
- Prior therapy with lapatinib
- Untreated brain metastasis or neurologically unstable CNS metastases
- Any severe or uncontrolled medical condition or other condition that could affect participation in this study including unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction </= 6 months prior to study entry
- Diarrhea > grade 1 at baseline
- Patients on a medication or herbal therapy known to inhibit CYP3A4
- Gastrointestinal tract disease resulting in the inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption or active peptic ulcer disease
- Ongoing ventricular cardiac dysrhythmias of grade >/= 2
- Subjects with a history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation >= 3 beats in a row)
- Serious cardiac arrhythmia requiring medication
- QTc interval > 500 msec
- Female patients who are pregnant or breast feeding, or adults who are of reproductive potential and are unwilling to refrain from conceiving a child during study treatment
- Patients unwilling or unable to comply with the protocol or provide informed consent
Studie plan
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 |
|---|---|
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Experimenteel: Cetuximab and lapatinib
All patients will receive cetuximab by IB weekly and daily doses of lapatinib orally in 3 week cycles with response assessed every 2 cycles.
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Cetuximab: 400 mg/m2 on Day 1 then 250 mg/m2 weekly Lapatinib: Start once daily on Day 1. Dose escalating cohorts:
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Maximum tolerated dose
Tijdsspanne: 12 months
|
The dose at which </= 1 out of 6 subjects experiences a dose limting toxicity
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12 months
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
response rate
Tijdsspanne: 12 months
|
How well tumor responds to treatment as measured by RECIST criteria
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12 months
|
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Pharmacokinetics
Tijdsspanne: 12 months
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Pharmacokinetics of lapatinib as measured by weekly trough levels
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12 months
|
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Genetic polymorphisms
Tijdsspanne: 12 months
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genetic polymorphisms in ABCG2, ABCB1, CYP3A4, and CYP3A5 wil be identified and counted
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12 months
|
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Genetic variations and activation status for EGFR and ErbB2 pathways
Tijdsspanne: 12 months
|
Genetic variations and activation status for EGFR amd ErbB2 pathways will be measured in pre- and post-therapy biopsies and assessed with western blots and IHC.
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12 months
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Medewerkers en onderzoekers
Sponsor
Medewerkers
Onderzoekers
- Hoofdonderzoeker: John F Deeken, M.D., Georgetown Univeristy Medical Center
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Ziekten van het spijsverteringsstelsel
- Neoplasmata
- Neoplasmata per site
- Gastro-intestinale neoplasmata
- Neoplasmata van het spijsverteringsstelsel
- Gastro-intestinale aandoeningen
- Colon Ziekten
- Darmziekten
- Intestinale neoplasmata
- Rectale ziekten
- Hoofd- en nekneoplasmata
- Colorectale neoplasmata
- Moleculaire mechanismen van farmacologische werking
- Enzymremmers
- Antineoplastische middelen
- Antineoplastische middelen, immunologisch
- Proteïnekinaseremmers
- Cetuximab
- Lapatinib
Andere studie-ID-nummers
- tykerb-itux 1
- 2010-218 (Andere identificatie: Georgetown University)
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