Clinical trial NCT01324479: Study of INC280 in Patients With c-MET Dependent Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Non-small cell lung cancer,
hepatocellular,
gastric,
renal cell,
c-MET,
refractory,
glioblastoma,
breast,
nasopharyngeal,
confirmed evidence of c-MET dysregulation
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-03-29
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence rate of dose-limiting toxicities and adverse events
timeFrame: 2 years
Secondary outcomes:
measure: Objective response by local investigator assessment
timeFrame: 2 years
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Chicago
country: United States
facility: University of Chicago SC
state: Illinois
city: Detroit
country: United States
facility: Karmanos Cancer Institute Wayne St Karmanos
state: Michigan
city: Nashville
country: United States
facility: Sarah Cannon Research Institute Dept of Onc
state: Tennessee
city: Houston
country: United States
facility: University of Texas/MD Anderson Cancer Center Dept of Onc
state: Texas
city: Westmead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Woolloongabba
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: La Tronche
country: France
facility: Novartis Investigative Site
city: LILLE Cédex
country: France
facility: Novartis Investigative Site
city: Strasbourg Cedex
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Gottingen
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Oldenburg
country: Germany
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Shatin, New Territories
country: Hong Kong
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Kfar Saba
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Meldola
country: Italy
facility: Novartis Investigative Site
state: FC
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Reggio Emilia
country: Italy
facility: Novartis Investigative Site
state: RE
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Gyeonggi do
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
state: The Netherlands
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Granada
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Oviedo
country: Spain
facility: Novartis Investigative Site
state: Asturias
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Zaragoza
country: Spain
facility: Novartis Investigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan ROC
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan ROC
city: Songkhla
country: Thailand
facility: Novartis Investigative Site
state: Hat Yai
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Schuler M, Berardi R, Lim WT, de Jonge M, Bauer TM, Azaro A, Gottfried M, Han JY, Lee DH, Wollner M, Hong DS, Vogel A, Delmonte A, Akimov M, Ghebremariam S, Cui X, Nwana N, Giovannini M, Kim TM. Molecular correlates of response to capmatinib in advanced non-small-cell lung cancer: clinical and biomarker results from a phase I trial. Ann Oncol. 2020 Jun;31(6):789-797. doi: 10.1016/j.annonc.2020.03.293. Epub 2020 Mar 30.
citation: Bang YJ, Su WC, Schuler M, Nam DH, Lim WT, Bauer TM, Azaro A, Poon RTP, Hong D, Lin CC, Akimov M, Ghebremariam S, Zhao S, Giovannini M, Ma B. Phase 1 study of capmatinib in MET-positive solid tumor patients: Dose escalation and expansion of selected cohorts. Cancer Sci. 2020 Feb;111(2):536-547. doi: 10.1111/cas.14254. Epub 2019 Dec 30.