- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT01285037
A Study of LY2801653 in Advanced Cancer
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.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 1
Kontakte und Standorte
Studienorte
-
-
Arizona
-
Tucson, Arizona, Vereinigte Staaten, 85724
- Arizona Cancer Center
-
-
District of Columbia
-
Washington, District of Columbia, Vereinigte Staaten, 20007
- Georgetown University Medical Center
-
-
New York
-
New York, New York, Vereinigte Staaten, 10029
- Mount Sinai Medical Center
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, Vereinigte Staaten, 19111
- Fox Chase Cancer Center
-
Philadelphia, Pennsylvania, Vereinigte Staaten, 19107
- Thomas Jefferson University
-
Philadelphia, Pennsylvania, Vereinigte Staaten, 19104
- University of Pennsylvania Hospital
-
-
Rhode Island
-
Providence, Rhode Island, Vereinigte Staaten, 02903
- Rhode Island Hospital
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Experimental: 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.
Andere Namen:
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.
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
---|---|
Recommended dose for phase 2 studies: Maximum tolerated dose
Zeitfenster: Baseline to study completion (estimated as 3 months)
|
Baseline to study completion (estimated as 3 months)
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
---|---|
Number of participants with tumor response
Zeitfenster: Part A: Baseline to study completion (estimated as 3 months)
|
Part A: Baseline to study completion (estimated as 3 months)
|
Clinical benefit rate (CBR)
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: Baseline to study completion (estimated as 3 months)
|
Baseline to study completion (estimated as 3 months)
|
Pharmacokinetics: Area under the concentration/time curve (AUC)
Zeitfenster: Cycle 1, Day 1; Cycle 2, Day 1
|
Cycle 1, Day 1; Cycle 2, Day 1
|
Pharmacokinetics: Maximum plasma concentration (Cmax)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: Baseline to study completion (estimated as 3 months)
|
Baseline to study completion (estimated as 3 months)
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Studienleiter: 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
Publikationen und hilfreiche Links
Allgemeine Veröffentlichungen
- 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.
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antiinfektiva
- Antivirale Mittel
- Enzym-Inhibitoren
- Antimetaboliten, antineoplastisch
- Antimetaboliten
- Antineoplastische Mittel
- Immunsuppressive Mittel
- Immunologische Faktoren
- Antineoplastische Mittel, immunologische
- Gemcitabin
- Ramucirumab
- Cetuximab
Andere Studien-ID-Nummern
- 13008
- I3O-MC-JSBA (Andere Kennung: Eli Lilly and Company)
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
Klinische Studien zur LY2801653
-
Eli Lilly and CompanyAbgeschlossen
-
Dana-Farber Cancer InstituteEli Lilly and CompanyBeendetKarzinom, nicht-kleinzellige Lunge | Solider KrebsVereinigte Staaten
-
Jacqueline Garcia, MDEli Lilly and CompanyAbgeschlossenRezidivierende akute myeloische Leukämie bei Erwachsenen | Refraktäre akute myeloische Leukämie bei ErwachsenenVereinigte Staaten
-
Eli Lilly and CompanyAbgeschlossenDarmkrebs | Mantelzell-Lymphom | Fortgeschrittener KrebsVereinigte Staaten, Frankreich, Vereinigtes Königreich
-
Eli Lilly and CompanyAktiv, nicht rekrutierendBauchspeicheldrüsenkrebs | Solider Krebs | Kutanes Melanom | Solide Tumoren mit hoher Mikrosatelliteninstabilität (MSI-H). | Brustkrebs (HR+HER2-)Frankreich, Spanien, Belgien, Korea, Republik von, Vereinigte Staaten, Taiwan, Kanada
-
Eli Lilly and CompanyAbgeschlossenNon-Hodgkin-Lymphom | Solider Krebs | Metastasierender Krebs | Cholangiokarzinom | Fortgeschrittener Krebs | Gallengangskarzinom | GallenblasenkarzinomJapan
-
Eli Lilly and CompanyAktiv, nicht rekrutierendMetastasierender Krebs | Fortgeschrittener Krebs | GallengangskrebsVereinigte Staaten, Belgien, Spanien, Australien, Tschechien, Dänemark, Korea, Republik von, Taiwan, Deutschland, Truthahn, Frankreich, Vereinigtes Königreich, Österreich, Russische Föderation, Mexiko, Ungarn, Argentinien, Schwede...