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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, 2017
Last verified: February 2017
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
Intervention Model: Parallel Assignment
Masking: No masking
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 ]
    ORR is defined as Complete Response (CR) and Partial Response (PR).

Secondary Outcome Measures:
  • Clinical Benefit Rate (CBR) [ Time Frame: at least 12 weeks ]
    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 ]
    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 ]
  • Overall Survival (OS) [ Time Frame: Estimated 12 months ]
  • Safety (Adverse Events [AEs] and Serious Adverse Events [SAEs]) [ Time Frame: Estimated 6 months ]
  • Change from baseline in quality of life measured using EQ-5D-5L and FACT-L [ Time Frame: Estimated 6 months ]
    Validated Quality of Life Questionnaires

Estimated Enrollment: 104
Study Start Date: May 2013
Estimated Study Completion Date: March 2017
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: neratinib monotherapy
240 mg neratinib
Drug: neratinib
240 mg orally, once daily with food, continuously in 21 day cycles
Experimental: neratinib plus temsirolimus
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   (Adult, Senior)
Sexes Eligible for Study:   All
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
University of California Los Angeles
Santa Monica, California, United States, 94040
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Massachusettes General Hospital
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
MD Anderson Cancer Center
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 ( EudraCT Number )
Study First Received: April 1, 2013
Last Updated: March 2, 2017

Keywords provided by Puma Biotechnology, Inc.:
Lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents processed this record on May 22, 2017