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NCT Number: NCT00838539

Study Evaluating 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.

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Key information

Conditions

Neoplasms Malignant Carcinoma

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Institut Gustave Roussy, Villejuif, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Neratinib

Drug

Other names: HKI-272

temsirolimus

Drug

Other names: Torisel, CCI-779

Primary outcomes

  1. 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.

  2. 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.

  3. 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

  4. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

Sponsors and collaborators

Lead sponsor

Puma Biotechnology, Inc.

Industry

Registry information

Official study title

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

Important dates

Study start
2009
Primary completion
2011
Study completion
2013
First posted
Feb 6, 2009
Registry last updated
Sep 18, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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