Clinical trial NCT00838539: Study Evaluating Neratinib In Combination With Temsirolimus In Subjects With Solid Tumors
Official title: A Phase 1 Study Of Neratinib In Combination With Temsirolimus In Subjects With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Malignant Carcinoma
Keywords: Neratinib
solid tumors
phase 1
dose finding study
HKI-272
Nerlynx
Temsirolimus
PB-272
Lead sponsor: Puma Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2009-02-06
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to identify the maximum tolerated dose(s) (MTD) of neratinib in combination with temsirolimus in subjects with solid tumors. This study will also include a preliminary evaluation of efficacy, and assessment of pharmacokinetic (PK) parameters of the combination.


Eligibility criteria: Inclusion Criteria:

* Pathologic diagnosis of advanced or metastatic solid tumor.
* Measurable disease per Response Criteria in Solid Tumors (RECIST criteria).
* Incurable cancer, with disease progression following at least 1 conventional or standard therapy for locally advanced or metastatic disease.
* Negative pregnancy test for women of child bearing potential.

Exclusion Criteria:

* Chronic treatment with corticosteroids.
* Primary central nervous system (CNS) tumors and active metastases.
* Presence of clinically significant or uncontrolled cardiac disease.
* Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom.
* Symptomatic or prior history of non-infectious interstitial pneumonitis.

Primary outcomes:
measure: Probability of Dose-Limiting Toxicity (DLT)
timeFrame: From first dose date to day 28
measure: Maximum Tolerated Dose (MTD) of Neratinib in Combination With Temsirolimus
timeFrame: From first dose date to day 28
measure: Maximum Tolerated Dose (MTD) of Temsirolimus in Combination With Neratinib
timeFrame: From first dose date to day 28
measure: Adverse Events Causing Dose Limiting Toxicities
timeFrame: From first dose date to day 21
Secondary outcomes:
measure: Best Overall Response
timeFrame: From first dose date to progression/death or last tumor assessment, up to 30 months
measure: Clinical Benefit Rate
timeFrame: From first dose date to progression/death or last tumor assessment, up to 30 months
measure: Objective Response Rate
timeFrame: From first dose date to progression/death or last tumor assessment, up to 30 months
measure: Area Under the Curve Tau
timeFrame: Week 4
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Biotechnology
name: Puma
role: STUDY_DIRECTOR
References:
citation: Gandhi L, Bahleda R, Tolaney SM, Kwak EL, Cleary JM, Pandya SS, Hollebecque A, Abbas R, Ananthakrishnan R, Berkenblit A, Krygowski M, Liang Y, Turnbull KW, Shapiro GI, Soria JC. Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2-dependent and other solid tumors. J Clin Oncol. 2014 Jan 10;32(2):68-75. doi: 10.1200/JCO.2012.47.2787. Epub 2013 Dec 9.