Study of INC280 in Patients With c-MET Dependent Advanced Solid Tumors

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01324479

Collaborator

(none)

131

Enrollment

Locations

Arm

64.1

Actual Duration (Months)

2.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will assess the safety and efficacy of INC280 in patients with solid tumors that are refractory to current treatment or for which there is not a current standard of care and whose tumors have dysregulation of the c-MET pathway.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: INC280	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

131 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Open-label Dose Escalation Study With Expansion to Assess the Safety and Tolerability of INC280 in Patients With c-MET Dependent Advanced Solid Tumors

Actual Study Start Date :

Feb 29, 2012

Actual Primary Completion Date :

Jul 4, 2017

Actual Study Completion Date :

Jul 4, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INC280	Drug: INC280

Arm

Intervention/Treatment

Experimental: INC280

Drug: INC280

Outcome Measures

Primary Outcome Measures

Incidence rate of dose-limiting toxicities and adverse events [2 years]

Secondary Outcome Measures

Objective response by local investigator assessment [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must have evidence of c-MET dysregulation from either local data or the results of molecular pre-screening evaluations.
Confirmed diagnosis of a solid tumor.
Measureable lesion.
Refractory to currently available treatment or no therapies available.
18 years or older.
ECOG performance status of 0, 1, or 2.
Obtained written informed consent.

Additional inclusion criteria for NSCLC patients EGFRwt with high c-MET expression:

Written documentation of EGFRwt NSCLC.
Written documentation of c-MET positivity.
Patients should not have received more than three prior lines of antineoplastic therapy for NSCLC.
Presence of at least one measurable lesion as determined by modified RECIST version 1.1

Exclusion Criteria:

HCC with liver dysfunction greater than Child-Pugh A. Previous treatment with a c-MET inhibitor or HGF-targeting therapy. Symptomatic CNS metastases that are neurologically unstable or requiring increasing doses of steroids to control their CNS disease.

Any CNS deficits. For patients with GBM, CNS symptoms grade 2 or greater. Subjects with significant or uncontrolled cardiovascular disease (eg, uncontrolled hypertension, peripheral vascular disease, congestive heart failure, cardiac arrhythmia, or acute coronary syndrome) within 6 months of starting study treatment or heart attack within 12 months of starting study treatment.

Receiving anti-epileptic drugs that are known to be strong inducers of CYP3A4. Prior or current anti-angiogenic therapy for patients with GBM. Radiation therapy within ≤ 4 weeks (< 12 for GBM) prior to the first dose of study drug or limited field radiotherapy within ≤ 2 weeks (< 12 weeks GBM) prior to the start of study treatment. Any persistent side effect of prior radiotherapy must be resolved to ≤ Grade 1 prior to the first dose of study drug.

Additional exclusion criteria for NSCLC patients EGFRwt with high c-MET expression:

Patients who have received more than three prior lines of antineoplastic therapies
Any unresolved toxicity (CTCAE grade > 1) from previous anti-cancer therapy or radiotherapy, except alopecia
Patients have received anti-cancer therapies within the following time frames prior to the first dose of study treatment:
Conventional cytotoxic chemotherapy: ≤4 weeks (≤6 weeks for nitrosoureas and mitomycin-C)
Biologic therapy (e.g., antibodies): ≤4 weeks
Non-cytotoxic small molecule therapeutics: ≤5 half-lives or ≤2 weeks (whichever is longer)
Other investigational agents: ≤4 weeks
Radiation therapy (palliative setting is allowed.): ≤4 weeks
Major surgery: ≤2 weeks

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
2	University of Chicago SC	Chicago	Illinois	United States	60637
3	Karmanos Cancer Institute Wayne St Karmanos	Detroit	Michigan	United States	48201
4	Sarah Cannon Research Institute Dept of Onc	Nashville	Tennessee	United States	37203
5	University of Texas/MD Anderson Cancer Center Dept of Onc	Houston	Texas	United States	77030-4009
6	Novartis Investigative Site	Westmead	New South Wales	Australia	2145
7	Novartis Investigative Site	Woolloongabba	Queensland	Australia	4102
8	Novartis Investigative Site	Ottawa	Ontario	Canada	K1H 8L6
9	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 2M9
10	Novartis Investigative Site	La Tronche		France	38700
11	Novartis Investigative Site	LILLE Cédex		France	59037
12	Novartis Investigative Site	Strasbourg Cedex		France	67091
13	Novartis Investigative Site	Essen		Germany	45147
14	Novartis Investigative Site	Frankfurt		Germany	60590
15	Novartis Investigative Site	Freiburg		Germany	79106
16	Novartis Investigative Site	Gottingen		Germany	37075
17	Novartis Investigative Site	Hannover		Germany	30625
18	Novartis Investigative Site	Oldenburg		Germany	26121
19	Novartis Investigative Site	Hong Kong		Hong Kong
20	Novartis Investigative Site	Shatin, New Territories		Hong Kong
21	Novartis Investigative Site	Haifa		Israel	3525408
22	Novartis Investigative Site	Kfar Saba		Israel	4428164
23	Novartis Investigative Site	Ramat Gan		Israel	5265601
24	Novartis Investigative Site	Tel Aviv		Israel	6423906
25	Novartis Investigative Site	Ancona	AN	Italy	60126
26	Novartis Investigative Site	Meldola	FC	Italy	47014
27	Novartis Investigative Site	Milano	MI	Italy	20133
28	Novartis Investigative Site	Milano	MI	Italy	20162
29	Novartis Investigative Site	Reggio Emilia	RE	Italy	42123
30	Novartis Investigative Site	Seoul	Gyeonggi Do	Korea, Republic of	03080
31	Novartis Investigative Site	Gyeonggi do	Korea	Korea, Republic of	10408
32	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	05505
33	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	06351
34	Novartis Investigative Site	Seoul	Seocho Gu	Korea, Republic of	06591
35	Novartis Investigative Site	Utrecht	The Netherlands	Netherlands	3508 GA
36	Novartis Investigative Site	Amsterdam		Netherlands	1066 CX
37	Novartis Investigative Site	Rotterdam		Netherlands	3075 EA
38	Novartis Investigative Site	Oslo		Norway	NO-0424
39	Novartis Investigative Site	Singapore		Singapore	169610
40	Novartis Investigative Site	Granada	Andalucia	Spain	18014
41	Novartis Investigative Site	Oviedo	Asturias	Spain	33006
42	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
43	Novartis Investigative Site	Madrid		Spain	28046
44	Novartis Investigative Site	Zaragoza		Spain	50009
45	Novartis Investigative Site	Tainan	Taiwan ROC	Taiwan	70403
46	Novartis Investigative Site	Taipei	Taiwan ROC	Taiwan	10041
47	Novartis Investigative Site	Songkhla	Hat Yai	Thailand	90110