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

August 17, 2018 updated by: Puma Biotechnology, Inc.

A Phase 1 Study Of Neratinib In Combination With Temsirolimus In Subjects With Solid Tumors

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

63

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Villejuif, France, 94805
        • Institut Gustave Roussy
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
      • Boston, Massachusetts, United States, 02115
        • Beth Israel Deaconess Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • HKI-272
Drug: Temsirolimus
Other Names:
  • Torisel, 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 Names:
  • HKI-272
Drug: Temsirolimus
Other Names:
  • Torisel, 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 Names:
  • HKI-272
Drug: Temsirolimus
Other Names:
  • Torisel, 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 Names:
  • HKI-272
Drug: Temsirolimus
Other Names:
  • Torisel, 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 Names:
  • HKI-272
Drug: Temsirolimus
Other Names:
  • Torisel, 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 Names:
  • HKI-272
Drug: Temsirolimus
Other Names:
  • Torisel, 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 Names:
  • HKI-272
Drug: Temsirolimus
Other Names:
  • Torisel, 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 Names:
  • HKI-272
Drug: Temsirolimus
Other Names:
  • Torisel, 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 Names:
  • HKI-272
Drug: Temsirolimus
Other Names:
  • Torisel, 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 Names:
  • HKI-272
Drug: Temsirolimus
Other Names:
  • Torisel, 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 Names:
  • HKI-272
Drug: Temsirolimus
Other Names:
  • Torisel, 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 Names:
  • HKI-272
Drug: Temsirolimus
Other Names:
  • Torisel, CCI-779

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Probability of Dose-Limiting Toxicity (DLT)
Time Frame: From first dose date to day 28
A DLT was defined as any dose-limiting Adverse Event related to neratinib + Temsirolimus as Grade 3 or higher nonhematologic toxicity (except neutropenia) or Grade 3 or higher diarrhea lasting >2 days with optimal antidiarrheal therapy etc.
From first dose date to day 28
Maximum Tolerated Dose (MTD) of Neratinib in Combination With Temsirolimus
Time Frame: From first dose date to day 28
Identification of the daily neratinib high-dose MTD in combination with weekly temsirolimus.
From first dose date to day 28
Maximum Tolerated Dose (MTD) of Temsirolimus in Combination With Neratinib
Time Frame: From first dose date to day 28
Identification of the weekly temsirolimus high-dose MTD in combination with daily neratinib
From first dose date to day 28
Adverse Events Causing Dose Limiting Toxicities
Time Frame: From first dose date to day 21

A DLT was defined as any dose-limiting adverse event (AE) related to neratinib + TEMSR as follows: [1] Grade 3 or 4 nonhematologic toxicity (Grade 3 or 4 nausea, vomiting, hyperglycemia, hypophosphatemia, hypertriglyceridemia, or hypercholesterolemia was not considered a DLT unless the subject was already receiving optimal medical therapy). [2] Grade 3 or 4 diarrhea lasting >2 days while subject was on optimal vigorous antidiarrheal therapy.

[3] Grade 4 neutropenia lasting >3 days or Grade 3 or 4 neutropenia of any duration with sepsis or a fever >38.5C. [4] Platelet value less than or equal to 25,000/mm3 or bleeding requiring a platelet transfusion. [5] Delayed recovery from toxicity, which delayed rescheduled re-treatment for >3 weeks. [6] Inability to maintain the original dose during the first 28 days of treatment (at least 21 doses of neratinib and 2 doses of TEMSR at the original specified dose) due to treatment-related toxicity.
From first dose date to day 21

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Overall Response
Time Frame: From first dose date to progression/death or last tumor assessment, up to 30 months
The best overall response was described using the data as reported by study center investigators per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
From first dose date to progression/death or last tumor assessment, up to 30 months
Clinical Benefit Rate
Time Frame: From first dose date to progression/death or last tumor assessment, up to 30 months
Percentage of subjects with a complete response, partial response, or stable disease >= 24 weeks, as determined by investigator assessment per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
From first dose date to progression/death or last tumor assessment, up to 30 months
Objective Response Rate
Time Frame: From first dose date to progression/death or last tumor assessment, up to 30 months
Percentage of subjects with a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
From first dose date to progression/death or last tumor assessment, up to 30 months
Area Under the Curve Tau
Time Frame: Week 4
Area Under the Curve tau of neratinib concentrations, collected at 2, 4, 8, and 24 hours post-neratinib administration, at the week 4 dose.
Week 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Puma Biotechnology, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2009

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

February 5, 2009

First Submitted That Met QC Criteria

February 5, 2009

First Posted (Estimate)

February 6, 2009

Study Record Updates

Last Update Posted (Actual)

September 18, 2018

Last Update Submitted That Met QC Criteria

August 17, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3144A1-2205 / B1891016

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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