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

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Puma Biotechnology, Inc. Identifier:
First received: April 1, 2013
Last updated: March 2, 2016
Last verified: March 2016
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.

Condition Intervention Phase
HER2-mutant Non-Small Cell Lung Cancer
Drug: neratinib
Drug: temsirolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Neratinib and Neratinib Plus Temsirolimus in Patients With Non-Small Cell Lung Cancer Carrying Known HER2 Activating Mutations

Resource links provided by NLM:

Further study details as provided by Puma Biotechnology, Inc.:

Primary Outcome Measures:
  • 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).

Secondary Outcome Measures:
  • 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

Estimated Enrollment: 104
Study Start Date: May 2013
Estimated Study Completion Date: December 2016
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
240 mg neratinib
Drug: neratinib
240 mg orally, once daily with food, continuously in 21 day cycles
Experimental: B
240 mg neratinib plus 8 mg temsirolimus with optional dose escalation to 15 mg temsirolimus
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

Detailed Description:

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. 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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 neratinib or mTOR inhibitor

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01827267

United States, California
City of Hope
Duarte, California, United States, 91010
UC Davis Cancer Center
Sacramento, California, United States, 95817
Santa Monica, California, United States, 94040
United States, Colorado
University of Colorado
Aurora, Colorado, United States
United States, Florida
Tampa, Florida, United States
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Massachusettes General Hospital
Boston, Massachusetts, United States, 02215
Dana Farber
Boston, Massachusetts, United States
United States, Missouri
Washington University
St. Louis, Missouri, United States
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
United States, Ohio
Ohio State University
Columbus, Ohio, United States
United States, Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Nashville, Tennessee, United States, 37232
United States, Texas
UT Southwestern
Dallas, Texas, United States
MD Anderson
Houston, Texas, United States, 77030
CHU de Grenoble Hopital Albert Michallon
Grenoble, France, 38043
CHRU de Lille - Hopital Calmette
Lille, France, 59037
Hopital Nord
Marseille, France, 13915
Hopitaux universitaires de Strasbourg Nouvel Hopital Civil
Strasbourg, France, 167091
CHU de Toulous Hopital Larre
Toulouse, France, 30030
Institut Gustave Roussy
Villejuif, France, 94805
Sponsors and Collaborators
Puma Biotechnology, Inc.
  More Information

Responsible Party: Puma Biotechnology, Inc. Identifier: NCT01827267     History of Changes
Other Study ID Numbers: PUMA-NER-4201  2012-004743-68 
Study First Received: April 1, 2013
Last Updated: March 2, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Puma Biotechnology, Inc.:
Lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Physiological Effects of Drugs processed this record on May 24, 2016