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

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00838539
• Other study ID #: 3144A1-2205 / B1891016
• Status: Completed
• Phase: Phase 1
• Start date: April 2009
• Est. completion date: December 2013

Study information

• Verified date: August 2018
• Source: Puma Biotechnology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: December 2013
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Malignant Carcinoma
• Neoplasms

Intervention

Drug:
• Neratinib

• Temsirolimus

Locations

Country	Name	City	State
France	Institut Gustave Roussy	Villejuif
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Puma Biotechnology, Inc.

Countries where clinical trial is conducted

United States,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Probability of Dose-Limiting Toxicity (DLT)	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
Primary	Maximum Tolerated Dose (MTD) of Neratinib in Combination With Temsirolimus	Identification of the daily neratinib high-dose MTD in combination with weekly temsirolimus.	From first dose date to day 28
Primary	Maximum Tolerated Dose (MTD) of Temsirolimus in Combination With Neratinib	Identification of the weekly temsirolimus high-dose MTD in combination with daily neratinib	From first dose date to day 28
Primary	Adverse Events Causing Dose Limiting Toxicities	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	Best Overall Response	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
Secondary	Clinical Benefit Rate	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
Secondary	Objective Response Rate	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
Secondary	Area Under the Curve Tau	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