Neratinib With and Without Temsirolimus for Patients With HER2 Activating Mutations in Non-Small Cell Lung Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Puma Biotechnology, Inc.
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier:
NCT01827267
First received: April 1, 2013
Last updated: April 15, 2014
Last verified: April 2014

April 1, 2013
April 15, 2014
May 2013
June 2014   (final data collection date for primary outcome measure)
Overall Response Rate (ORR) [ Time Frame: minimum 21 days ] [ Designated as safety issue: No ]
ORR is defined as Complete Response (CR) and Partial Response (PR) after receiving at least one prior regimen of chemotherapy
Same as current
Complete list of historical versions of study NCT01827267 on ClinicalTrials.gov Archive Site
  • Clinical Benefit Rate (CBR) [ Time Frame: at least 12 weeks ] [ Designated as safety issue: No ]
    CBR is defined as the percentage of patients with CR plus PR plus Stable Disease (SD)
  • Duration of Response (DOR) [ Time Frame: Estimated 6 months ] [ Designated as safety issue: No ]
    DOR is defined as the date when criterion of CR or PR is first met and subsequently confirmed (whichever status is recorded first) to the first date of documented disease progression
  • Progression Free Survival (PFS) [ Time Frame: Estimated 6 months ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Estimated 12 months ] [ Designated as safety issue: No ]
  • Safety (Adverse Events [AEs] and Serious Adverse Events [SAEs]) [ Time Frame: Estimated 6 months ] [ Designated as safety issue: Yes ]
  • Change from baseline in quality of life measured using EQ-5D-5L and FACT-L [ Time Frame: Estimated 6 months ] [ Designated as safety issue: No ]
    Validated Quality of Life Questionnaires
Same as current
Not Provided
Not Provided
 
Neratinib With and Without Temsirolimus for Patients With HER2 Activating Mutations in Non-Small Cell Lung Cancer
A Phase 2 Study of Neratinib and Neratinib Plus Temsirolimus in Patients With Non-Small Cell Lung Cancer Carrying Known HER2 Activating Mutations

This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter, multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus combination therapy in patients with non-small cell lung cancer (NSCLC) who have documented somatic HER2 mutations and who have received at least one prior cytotoxic chemotherapy regimen.

This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter, multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus combination therapy in patients with NSCLC who have documented somatic HER2 mutations and who have received at least one prior cytotoxic chemotherapy regimen. Patients will be randomized at study entry into 1 of 2 treatment arms:

  • Arm A: neratinib 240 mg orally once daily,
  • Arm B: neratinib 240 mg orally once daily plus temsirolimus 8 mg once weekly by intravenous (IV) infusion.

In the case of disease progression, patients initially assigned to the neratinib monotherapy arm will be given the option to add temsirolimus 8 mg IV once weekly.

All patients on combination therapy may be dose-escalated with respect to temsirolimus dose to 15 mg/week at the end of first cycle of treatment with the combination, if well tolerated and at the physician's discretion. In the event that the neratinib 240 mg/day plus temsirolimus 15 mg/week dose is not well tolerated, the patient will be subsequently dose reduced back to neratinib 240 mg/day plus temsirolimus 8 mg/week.

Dosing will be continuous on nominal 3-week cycles until evidence of progressive disease, unacceptable toxicity, or patient withdrawal of consent.

All eligible patients enrolled will have their disease measured radiographically at baseline. Patients will undergo radiographic evaluation of their disease every 6 weeks until disease progression or withdrawal from the study.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HER2-mutant Non-Small Cell Lung Cancer
  • Drug: neratinib
    240 mg orally, once daily with food, continuously in 21 day cycles
  • Drug: temsirolimus
    8 mg or 15 mg weekly by IV infusion
    Other Name: Torisel
  • Experimental: A
    240 mg neratinib
    Intervention: Drug: neratinib
  • Experimental: B
    240 mg neratinib plus 8 mg temsirolimus with optional dose escalation to 15 mg temsirolimus
    Interventions:
    • Drug: neratinib
    • Drug: temsirolimus
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
104
April 2016
June 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Aged ≥18 years at the time of signing the informed consent.
  • Histologically confirmed diagnosis of NSCLC, advanced (stage IIIB) or metastatic (stage IV).
  • Documented somatic ErbB2 (HER2) activating mutation.

Exclusion Criteria:

  • Previous treatment with any investigational agent ≤30 days prior to the initiation of investigational products.
  • Prior exposure to tyrosine kinase inhibitor including neratinib, lapatinib, and afatinib (excluding dacomitinib), or mTOR inhibitor.

Note: There are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

Both
18 Years and older
No
Contact: Puma Biotechnology Clinical Operations +1-424-248-6500 clinicaltrials@pumabiotechnology.com
United States,   France
 
NCT01827267
PUMA-NER-4201, 2012-004743-68
No
Puma Biotechnology, Inc.
Puma Biotechnology, Inc.
Not Provided
Not Provided
Puma Biotechnology, Inc.
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP