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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P75+ for phase_1

Timeline

Completed

Started Apr 2009

Longer than P75 for phase_1

Geographic Reach

2 countries

5 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

4.7 years study duration

First Submitted

Initial submission to the registry

February 5, 2009

Completed

1 day until next milestone

First Posted

Study publicly available on registry

February 6, 2009

Completed

2 months until next milestone

Study Start

First participant enrolled

April 1, 2009

Completed

2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2011

Completed

2.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2013

Completed

4.2 years until next milestone

Results Posted

Study results publicly available

February 26, 2018

Completed

Last Updated

September 18, 2018

Status Verified

August 1, 2018

Enrollment Period

2.2 years

First QC Date

February 5, 2009

Results QC Date

August 10, 2017

Last Update Submit

August 17, 2018

Conditions

Neoplasms Malignant Carcinoma

Keywords

Neratinibsolid tumorsphase 1dose finding studyHKI-272NerlynxTemsirolimusPB-272

Outcome Measures

Primary Outcomes (4)

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
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
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
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 Outcomes (4)

Best Overall Response
From first dose date to progression/death or last tumor assessment, up to 30 months
Clinical Benefit Rate
From first dose date to progression/death or last tumor assessment, up to 30 months
Objective Response Rate
From first dose date to progression/death or last tumor assessment, up to 30 months
Area Under the Curve Tau
Week 4

Study Arms (12)

Neratinib and Temsirolimus (Dose level 1)

EXPERIMENTAL

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