A Study of LY2801653 in Advanced Cancer
19. februar 2018 oppdatert av: Eli Lilly and Company
A Phase 1 Study of LY2801653 in Patients With Advanced Cancer
Part A- The purpose of this study is to determine a safe dose of LY2801653 to be given to participants with advanced cancer and to determine any side effects that may be associated with LY2801653 in this participant population. Efficacy measures will be used to assess the activity of LY2801653.
Part B- The dose determined in Part A will be used along with efficacy measures to assess the activity of LY2801653 in participants with adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma (HNSCC), uveal melanoma with liver metastasis, and cholangiocarcinoma.
Part C - the objective of Part C is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with HNSCC when taken with standard doses of cetuximab Part D - the objective of Part D is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with cholangiocarcinoma when taken with a standard dose of cisplatin.
Part E - the objective of Part E is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with cholangiocarcinoma when taken with gemcitabine plus cisplatin.
Part F - the objective of Part F is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with gastric cancer when taken with ramucirumab.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
Parts C and D were added to the registration in November, 2013, per protocol amendment.
Parts E and F were added to the registration in February, 2015, per protocol amendment.
Studietype
Intervensjonell
Registrering (Faktiske)
190
Fase
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
-
-
Arizona
-
Tucson, Arizona, Forente stater, 85724
- Arizona Cancer Center
-
-
District of Columbia
-
Washington, District of Columbia, Forente stater, 20007
- Georgetown University Medical Center
-
-
New York
-
New York, New York, Forente stater, 10029
- Mount Sinai Medical Center
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, Forente stater, 19111
- Fox Chase Cancer Center
-
Philadelphia, Pennsylvania, Forente stater, 19107
- Thomas Jefferson University
-
Philadelphia, Pennsylvania, Forente stater, 19104
- University of Pennsylvania Hospital
-
-
Rhode Island
-
Providence, Rhode Island, Forente stater, 02903
- Rhode Island Hospital
-
-
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:
- Part A- Diagnosed with advanced and/or metastatic cancer during dose escalation
- Part B- Diagnosed with adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma, uveal melanoma with liver with metastasis, or cholangiocarcinoma
- Part C - Diagnosed with head and neck squamous cell carcinoma and have received at least one prior platinum-based systemic therapy
- Part D - Diagnosed with cholangiocarcinoma and have not received more than 1 prior systemic therapy
- Part E - Diagnosed with cholangiocarcinoma, either intrahepatic or extrahepatic, that is unresectable, recurrent, or metastatic. Participants must not have received prior systemic front line therapy for metastatic or resectable disease (i.e. participants may have received adjuvant gemcitabine but have not yet received gemcitabine/cisplatin for recurrent metastatic disease). Participants must be, in the opinion of the investigator, an appropriate candidate for experimental therapy. Participants should be evaluated for the need to undergo biliary drainage by stent placement prior to study participation. Participants should have adequate biliary drainage with no unresolved biliary obstruction.
- Part F - Histologically- or cytologically-confirmed gastric carcinoma, including gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma (participants with adenocarcinoma of the distal esophagus are eligible if the primary tumor involves the GEJ). Participants must be ramucirumab naïve. Participants must be, in the opinion of the investigator, an appropriate candidate for experimental therapy. human epidermal growth factor receptor 2 (HER2)/neu status should be documented, if known.
- Must be at least 18 years of age
- Adequate hematologic, renal, and liver functions
- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
- Ability to swallow capsules, with the exception of head and neck squamous cell carcinoma participants who may have study drug crushed and administered through a feeding tube
Exclusion Criteria:
- Have serious preexisting medical conditions that would preclude participation in the study
- Have a chronic underlying infection
- Have symptomatic central nervous system (CNS) malignancy or metastasis
- Have current acute or chronic leukemia
- Are pregnant or lactating
- Have hepatocellular cancer, liver cirrhosis with a Child-Pugh stage of B or higher, or have received a liver transplant
- Have a history of congestive heart failure with a New York Heart Association class greater than 2, unstable angina, recent myocardial infarction (within 6 months of study enrollment), transient ischemic attacks, stroke, or arterial or venous vascular disease
- Have a QTc interval greater than 470 msec
- For participants in Part B, C, D, E, and F, a tumor tissue sample is mandatory, when safe and feasible, for biomarker analysis
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: LY2801653
This study consists of a dose escalation of LY2801653 (Part A) followed by dose confirmation cohorts in four tumor types (adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma, uveal melanoma with liver metastasis, and cholangiocarcinoma) (Part B). Part C consists of dose determination for LY2801653 in combination with cetuximab in participants with head and neck squamous cell carcinoma followed by an expansion cohort. Part D consists of dose determination for LY2801653 in combination with cisplatin in participants with cholangiocarcinoma followed by an expansion cohort. Part E consists of dose determination for LY2801653 in combination with gemcitabine and cisplatin. Part F consists of dose determination for LY2801653 in combination with ramicirumab. |
LY2801653 given orally once daily during 28-day cycles.
Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
Cetuximab given via IV infusion once weekly, 400mg/m2 for first dose and 250mg /m2 for subsequent doses.
If LY2801653 treatment is stopped due to toxicity after a minimum of 4 cycles, cetuximab may be continued until disease progression.
In the event cetuximab treatment is stopped, participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
Cisplatin given via IV infusion once a week for 2 weeks and then every 3 weeks.
If the LY2801653 is terminated for LY2801653-related toxicity after a minimum of 4 cycles, cisplatin may be continued as monotherapy until progression of disease.
Participants discontinuing cisplatin therapy may be allowed to continue single agent LY2801653 if they are receiving clinical benefit.
Gemcitabine given via IV infusion once a week for 2 weeks and then every 3 weeks.
If the LY2801653 is terminated for LY2801653-related toxicity after a minimum of 4 cycles, gemcitabine may be continued as monotherapy until progression of disease.
Participants discontinuing gemcitabine therapy may be allowed to continue single agent LY2801653 if they are receiving clinical benefit.
Andre navn:
Ramucirumab given via IV infusion every 2 weeks in a 28-day treatment cycle.
Treatment with ramucirumab may continue until excessive toxicity or evidence of disease progression.
In the absence of disease progression, treatment with LY2801653 may continue even if ramucirumab is discontinued provided no dose limiting toxicity related to LY2801653 is present.
In the event that LY2801653 is discontinued, treatment with ramucirumab may be continued if there is no dose limiting toxicity related to ramucirumab.
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Recommended dose for phase 2 studies: Maximum tolerated dose
Tidsramme: Baseline to study completion (estimated as 3 months)
|
Baseline to study completion (estimated as 3 months)
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Number of participants with tumor response
Tidsramme: Part A: Baseline to study completion (estimated as 3 months)
|
Part A: Baseline to study completion (estimated as 3 months)
|
|
Clinical benefit rate (CBR)
Tidsramme: Parts B, C, D: Baseline to study completion (estimated as 3 months)
|
Parts B, C, D: Baseline to study completion (estimated as 3 months)
|
|
Progression free survival (PFS)
Tidsramme: Parts B, C, D: Baseline to study completion (estimated as up to 6 months)
|
Parts B, C, D: Baseline to study completion (estimated as up to 6 months)
|
|
Duration of response
Tidsramme: Parts B, C, D: Baseline to study completion (estimated as up to 6 months)
|
Parts B, C, D: Baseline to study completion (estimated as up to 6 months)
|
|
Number of participants with clinically significant effects
Tidsramme: Baseline to study completion (estimated as 3 months)
|
Baseline to study completion (estimated as 3 months)
|
|
Pharmacokinetics: Area under the concentration/time curve (AUC)
Tidsramme: Cycle 1, Day 1; Cycle 2, Day 1
|
Cycle 1, Day 1; Cycle 2, Day 1
|
|
Pharmacokinetics: Maximum plasma concentration (Cmax)
Tidsramme: Cycle 1, Day 1; Cycle 2, Day 1
|
Cycle 1, Day 1; Cycle 2, Day 1
|
|
Maximum tolerated dose (MTD) of LY2801653 in combination with cetuximab for phase 2 studies in HNSCC
Tidsramme: Baseline to study completion (estimated as 3 months)
|
Baseline to study completion (estimated as 3 months)
|
|
Maximum tolerated dose (MTD) of LY2801653 in combination with cisplatin for phase 2 studies in cholangiocarcinoma
Tidsramme: Baseline to study completion (estimated as 3 months)
|
Baseline to study completion (estimated as 3 months)
|
|
Maximum tolerated dose (MTD) of LY2801653 in combination with gemcitabine plus cisplatin for phase 2 studies in cholangiocarcinoma
Tidsramme: Baseline to study completion (estimated as 3 months)
|
Baseline to study completion (estimated as 3 months)
|
|
Maximum tolerated dose (MTD) of LY2801653 in combination with ramucirumab for phase 2 studies in gastric carcinoma
Tidsramme: Baseline to study completion (estimated as 3 months)
|
Baseline to study completion (estimated as 3 months)
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Studieleder: Call 1-877-CTLILLY (1-817-285-4559) or 1-317-615-4559 Mon - Fri 9AM to 5PM Eastern time (UTC/GMT - 5hours, EST), Eli Lilly and Company
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.
Generelle publikasjoner
- He AR, Cohen RB, Denlinger CS, Sama A, Birnbaum A, Hwang J, Sato T, Lewis N, Mynderse M, Niland M, Giles J, Wallin J, Moser B, Zhang W, Walgren R, Plimack ER. First-in-Human Phase I Study of Merestinib, an Oral Multikinase Inhibitor, in Patients with Advanced Cancer. Oncologist. 2019 Sep;24(9):e930-e942. doi: 10.1634/theoncologist.2018-0411. Epub 2019 Mar 4.
- Yan SB, Peek VL, Ajamie R, Buchanan SG, Graff JR, Heidler SA, Hui YH, Huss KL, Konicek BW, Manro JR, Shih C, Stewart JA, Stewart TR, Stout SL, Uhlik MT, Um SL, Wang Y, Wu W, Yan L, Yang WJ, Zhong B, Walgren RA. LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models. Invest New Drugs. 2013 Aug;31(4):833-44. doi: 10.1007/s10637-012-9912-9. Epub 2012 Dec 29.
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 (Faktiske)
9. september 2009
Primær fullføring (Faktiske)
21. juli 2017
Studiet fullført (Faktiske)
11. september 2017
Datoer for studieregistrering
Først innsendt
26. januar 2011
Først innsendt som oppfylte QC-kriteriene
26. januar 2011
Først lagt ut (Anslag)
27. januar 2011
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
20. februar 2018
Siste oppdatering sendt inn som oppfylte QC-kriteriene
19. februar 2018
Sist bekreftet
1. februar 2018
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Anti-infeksjonsmidler
- Antivirale midler
- Enzymhemmere
- Antimetabolitter, antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Antineoplastiske midler, immunologiske
- Gemcitabin
- Ramucirumab
- Cetuximab
Andre studie-ID-numre
- 13008
- I3O-MC-JSBA (Annen identifikator: Eli Lilly and Company)
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. .