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Study Evaluating Neratinib In Combination With Temsirolimus In Subjects With Solid Tumors

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ClinicalTrials.gov Identifier: NCT00838539
Recruitment Status : Completed
First Posted : February 6, 2009
Results First Posted : February 26, 2018
Last Update Posted : February 26, 2018
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.

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.

Condition or disease Intervention/treatment Phase
Neoplasms Malignant Carcinoma Drug: Neratinib Drug: Temsirolimus Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 63 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study Of Neratinib In Combination With Temsirolimus In Subjects With Solid Tumors
Study Start Date : April 2009
Actual Primary Completion Date : June 2011
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Neratinib and Temsirolimus (Dose level 1)
Neratinib 120 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Drug: Neratinib
Other Name: HKI-272
Drug: Temsirolimus
Other Name: Torisel, temsr, CCI-779
Experimental: Neratinib and Temsirolimus (Dose level 2)
Neratinib 120 mg and Temsirolimus 25 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Drug: Neratinib
Other Name: HKI-272
Drug: Temsirolimus
Other Name: Torisel, temsr, CCI-779
Experimental: Neratinib and Temsirolimus (Dose level 3)
Neratinib 120 mg and Temsirolimus 50 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Drug: Neratinib
Other Name: HKI-272
Drug: Temsirolimus
Other Name: Torisel, temsr, CCI-779
Experimental: Neratinib and Temsirolimus (Dose level 4)
Neratinib 120 mg and Temsirolimus 75 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Drug: Neratinib
Other Name: HKI-272
Drug: Temsirolimus
Other Name: Torisel, temsr, CCI-779
Experimental: Neratinib and Temsirolimus (Dose level 5)
Neratinib 160 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Drug: Neratinib
Other Name: HKI-272
Drug: Temsirolimus
Other Name: Torisel, temsr, CCI-779
Experimental: Neratinib and Temsirolimus (Dose level 6)
Neratinib 160 mg and Temsirolimus 25 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Drug: Neratinib
Other Name: HKI-272
Drug: Temsirolimus
Other Name: Torisel, temsr, CCI-779
Experimental: Neratinib and Temsirolimus (Dose level 7)
Neratinib 160 mg and Temsirolimus 50 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Drug: Neratinib
Other Name: HKI-272
Drug: Temsirolimus
Other Name: Torisel, temsr, CCI-779
Experimental: Neratinib and Temsirolimus (Dose level 8)
Neratinib 160 mg and Temsirolimus 75 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Drug: Neratinib
Other Name: HKI-272
Drug: Temsirolimus
Other Name: Torisel, temsr, CCI-779
Experimental: Neratinib and Temsirolimus (Dose level 9)
Neratinib 200 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Drug: Neratinib
Other Name: HKI-272
Drug: Temsirolimus
Other Name: Torisel, temsr, CCI-779
Experimental: Neratinib and Temsirolimus (Dose level 10)
Neratinib 200 mg and Temsirolimus 25 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Drug: Neratinib
Other Name: HKI-272
Drug: Temsirolimus
Other Name: Torisel, temsr, CCI-779
Experimental: Neratinib and Temsirolimus (Dose level 11)
Neratinib 200 mg and Temsirolimus 50 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Drug: Neratinib
Other Name: HKI-272
Drug: Temsirolimus
Other Name: Torisel, temsr, CCI-779
Experimental: Neratinib and Temsirolimus (Dose level 12)
Neratinib 240 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Drug: Neratinib
Other Name: HKI-272
Drug: Temsirolimus
Other Name: Torisel, temsr, CCI-779



Primary Outcome Measures :
  1. Dose-Limiting Toxicity (DLT) Incidence to Evaluate the Maximum Tolerated Dose (MTD) Toxicity Contour of the Combination of Neratinib and Temsirolimus. [ Time Frame: From first dose date to day 28 ]

    The Maximum Tolerated Dose (MTD) contour based on dose combinations in which the probability of a DLT was <1/3 (<33.3%).

    A DLT was defined as any dose-limiting AE related to neratinib + TEMSR as Grade 3 or higher nonhematologic toxicity (except neutropenia) or Grade 3 or higher diarrhea lasting >2 days with optimal antidiarrheal therapy etc.


  2. Identify the Recommended Phase 2 Dose [ Time Frame: From first dose date to day 28 ]
    Identification of the neratinib high-dose MTD in combination with temsirolimus, and identification of the temsirolimus high-dose MTD in combination with Neratinib.


Secondary Outcome Measures :
  1. Best Overall Response [ Time Frame: From first dose date to progression/death or last tumor assessment ]
    The best overall response and duration of response (for subjects who achieved an objective response) were described using the data as reported by study center investigators.

  2. Clinical Benefit Rate (CBR) [ Time Frame: From first dose date to progression/death or last tumor assessment ]
    Clinical benefit rate by neratinib dose level is the number of subjects with a CR, PR, or SD >= 24 weeks, as determined by RECIST per investigator assessment.

  3. Objective Response Rate (ORR) [ Time Frame: From first dose date to progression/death or last tumor assessment ]
    The objective response rate (ORR) is the number of subjects with a complete response (CR) or partial response (PR).

  4. Assess Pharmacokinetic Parameters of Neratinib and Temsirolimus in Combination [ Time Frame: Week 4 ]
    AUC tau of neratinib concentrations at various dose levels with various dose levels of temsirolimus.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00838539


Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
France
Institut Gustave Roussy
Villejuif, France, 94805
Sponsors and Collaborators
Puma Biotechnology, Inc.
Investigators
Study Director: Puma Biotechnology

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT00838539     History of Changes
Other Study ID Numbers: 3144A1-2205
B1891016
First Posted: February 6, 2009    Key Record Dates
Results First Posted: February 26, 2018
Last Update Posted: February 26, 2018
Last Verified: August 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Puma Biotechnology, Inc.:
Neratinib
solid tumors
phase 1
dose finding study
HKI-272
Nerlynx
Temsirolimus
PB-272

Additional relevant MeSH terms:
Everolimus
Sirolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents