NCT00741260|CompletedPhase 1ResultsFDA Drug

Study Evaluating The Combination Of Neratinib And Capecitabine In Solid Tumors And Breast Cancer

A Phase 1/2, Open-Label Study Of Neratinib (HKI-272) In Combination With Capecitabine In Subjects With Solid Tumors And ErbB-2 Positive Metastatic Or Locally Advanced Breast Cancer

Puma Biotechnology, Inc.ClinicalTrials.gov

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1 other identifier

3144A1-2206 / B1891017

Study Type

interventional

Target

105

Locations

11 countries

Sites

Timeline

RegisteredAug 2008

StartedDec 2008

CompletionJun 2018

Brief Summary

This is a world wide phase 1/2, open-label, study of neratinib in combination with capecitabine, conducted in 2 parts. In Part 1, 3 to 9 subjects with solid tumors will be enrolled in each dose group of the combination of neratinib and capecitabine. Each subject will participate in only 1 dose group. Additional subjects may be included at any dose level to further assess the safety and tolerability at that dose level. In Part 2, up to 60 subjects with erbB-2 positive metastatic breast cancer will receive treatment with the combination of neratinib and capecitabine at the maximum tolerated dose level, as determined in Part 1. In addition 20 subjects with prior lapatinib exposure will be enrolled in Part 2. Depending on the safety and activity profile observed during the dose escalation phase, the dose selected for Part 2 may be adjusted, if appropriate. In case one test article of the combination is discontinued due to intolerance the other test article can be administered alone. The primary objectives of Part 1 are to assess the safety and tolerability, and to define the maximum tolerated dose (MTD) of neratinib in combination with capecitabine in subjects with advanced solid tumors. The primary objective of Part 2 of this study is to confirm the MTD determined in Part 1. The secondary objective of Part 1 is to collect information on preliminary anti-tumor activity of the combination of neratinib and capecitabine. Secondary objectives for Part 2 are to collect pharmacokinetic information and to obtain additional efficacy data, such as Objective Response Rate, for subjects with erbB-2 positive breast cancer treated at the MTD of neratinib + capecitabine.

Trial Health

On Track

Trial Health Score

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

Enrollment

105

participants targeted

Target at P75+ for phase_1 breast-cancer

Timeline

Completed

Started Dec 2008

Longer than P75 for phase_1 breast-cancer

Geographic Reach

11 countries

37 active sites

Status

completed

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

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

9.5 years study duration

First Submitted

Initial submission to the registry

August 22, 2008

Completed

4 days until next milestone

First Posted

Study publicly available on registry

August 26, 2008

Completed

4 months until next milestone

Study Start

First participant enrolled

December 9, 2008

Completed

1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2010

Completed

7 years until next milestone

Results Posted

Study results publicly available

November 9, 2017

Completed

7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2018

Completed

Last Updated

September 5, 2018

Status Verified

August 1, 2018

Enrollment Period

1.9 years

First QC Date

August 22, 2008

Results QC Date

August 10, 2017

Last Update Submit

August 7, 2018

Conditions

Breast Cancer

Keywords

Solid TumorerbB2+ Breast CancerPrior trastuzumabMetastaticNeratinibHKI-272NerlynxHER2PB-272

Outcome Measures

Primary Outcomes (3)

Number of Participants With Dose Limiting Toxicities
Number of participants reporting Adverse Events Causing Dose Limiting Toxicities (DLT).
From first dose date to day 21
Maximum Tolerated Dose (MTD) of Neratinib
MTD reflects the highest dose of neratinib plus capeciteabine that did not cause a selected Grade 3 toxicity in \>= 2 participants, which is any of 1) Grade 3 or 4 non-hematologic toxicity (Grade 3 asthenia was not considered a DLT unless lasting \>3 days, 2) Grade 3 diarrhea lasting \>2 days on optimal medical therapy or associated with fever or dehydration. 3) Grade 4 neutropenia lasting ≥ 3 days or Grade 4 febrile neutropenia, 4) Grade 4 thrombocytopenia lasting ≥3 days or associated with bleeding or requiring platelet transfusion, 5) Delayed recovery \[to ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline\] from one of the above listed toxicities that were related to neratinib and/or capecitabine that delayed the initiation of the next dose by more than 3 weeks.
From first dose date to day 21.
Maximum Tolerated Dose (MTD) of Capecitabine
MTD reflects the highest dose of capecitabine in combination with neratinib that did not cause a selected Grade 3 toxicity in \>= 2 participants, which is any of 1) Grade 3 or 4 non-hematologic toxicity (Grade 3 asthenia was not considered a DLT unless lasting \>3 days, 2) Grade 3 diarrhea lasting \>2 days on optimal medical therapy or associated with fever or dehydration. 3) Grade 4 neutropenia lasting ≥ 3 days or Grade 4 febrile neutropenia, 4) Grade 4 thrombocytopenia lasting ≥3 days or associated with bleeding or requiring platelet transfusion, 5) Delayed recovery \[to ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline\] from one of the above listed toxicities that were related to neratinib and/or capecitabine that delayed the initiation of the next dose by more than 3 weeks.
From first dose date to day 21.

Secondary Outcomes (3)

Overall Response Rate
From first dose date to progression or last tumor assessment, up to three years.
Clinical Benefit Rate
From first dose date to progression or last tumor assessment, up to three years.
Duration of Response
From start date of response to first PD/death, up to three years.