Trial Outcomes & Findings for Study Evaluating Safety And Tolerability, Solid Tumor (NCT NCT00768469)

Last Updated: 2018-11-19

Results Overview

The incidence of DLTs in subjects with advanced solid tumors, treated with neratinib in combination with paclitaxel 80 mg/m\^2. DLT was defined as any neratinib plus paclitaxel related Grade 3 or 4 nonhematologic toxicity or Grade 4 hematologic toxicity with few exceptions.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

10 participants

Primary outcome timeframe

From first dose day through day 28.

Results posted on

2018-11-19

Participant Flow

Participant milestones

Participant milestones
Measure	Nera 160 + Pac Neratinib 160 mg + Paclitaxel 80 mg/m\^2	Nera 240 + Pac Neratinib 240 mg + Paclitaxel 80 mg/m\^2
Overall Study STARTED	3	7
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	3	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Nera 160 + Pac Neratinib 160 mg + Paclitaxel 80 mg/m\^2	Nera 240 + Pac Neratinib 240 mg + Paclitaxel 80 mg/m\^2
Overall Study Adverse Event	0	2
Overall Study Disease Progression	3	4
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Study Evaluating Safety And Tolerability, Solid Tumor

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nera 160 + Pac n=3 Participants Neratinib 160 mg + Paclitaxel 80 mg/m\^2	Nera 240 + Pac n=7 Participants Neratinib 240 mg + Paclitaxel 80 mg/m\^2	Total n=10 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Continuous	49.67 years STANDARD_DEVIATION 10.12 • n=5 Participants	53.14 years STANDARD_DEVIATION 8.07 • n=7 Participants	52.10 years STANDARD_DEVIATION 8.31 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Japanese	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: From first dose day through day 28.

Population: Patients with at least one dose of neratinib.

Outcome measures

Outcome measures
Measure	Nera 160 + Pac n=3 Participants Neratinib 160 mg + Paclitaxel 80 mg/m\^2	Nera 240 + Pac n=7 Participants Neratinib 240 mg + Paclitaxel 80 mg/m\^2
Dose Limiting Toxicity (DLT) - Percentage of Participants With DLT Events	0 percentage of participants.	0 percentage of participants.

PRIMARY outcome

Timeframe: From first dose day through day 28.

Population: Patients with at least one dose of neratinib.

The maximum tolerated dose of neratinib, as determined by the incidence of DLTs, in combination with paclitaxel 80 mg/m\^2, in subjects with advanced solid tumors.

Outcome measures

Outcome measures
Measure	Nera 160 + Pac n=10 Participants Neratinib 160 mg + Paclitaxel 80 mg/m\^2	Nera 240 + Pac Neratinib 240 mg + Paclitaxel 80 mg/m\^2
Maximum Tolerated Dose	240 mg	—

SECONDARY outcome

Timeframe: From first dose date to progression/death or last tumor assessment, up to 78 weeks.

Population: Subjects who met the eligibility criteria, received at least 2 weeks of neratinib and at least 2 doses of paclitaxel, and underwent at least 1 follow-up tumor assessment at approximately cycle 2 (week 8). In the case of disease progression prior to week 8, a clinical assessment of progressive disease (PD) was adequate.

Percentage of participants with partial response (PR) or complete response (CR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.

Outcome measures

Outcome measures
Measure	Nera 160 + Pac n=3 Participants Neratinib 160 mg + Paclitaxel 80 mg/m\^2	Nera 240 + Pac n=6 Participants Neratinib 240 mg + Paclitaxel 80 mg/m\^2
Objective Response Rate	33.3 percentage of participants Interval 0.8 to 90.6	50.0 percentage of participants Interval 11.8 to 88.2

SECONDARY outcome

Timeframe: From first dose date to progression/death, up to 78 weeks.

Number of weeks between the date of the first dose of test article and the first date of disease recurrence or progression, or death due to any cause, was documented, censored at the last evaluation, investigator assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (v1.0), as at least a 20% increase in the sum of the longest diameters (LD) of target lesions, taking as reference the nadir LD, meaning the smallest sum of the LDs recorded since the treatment started; or unequivocal progression of existing nontarget lesions; or the appearance of any new lesions.

Outcome measures

Outcome measures
Measure	Nera 160 + Pac n=3 Participants Neratinib 160 mg + Paclitaxel 80 mg/m\^2	Nera 240 + Pac n=6 Participants Neratinib 240 mg + Paclitaxel 80 mg/m\^2
Progression Free Survival	15.9 weeks Interval 8.4 to 78.1	37.1 weeks Interval 24.4 to Insufficient number of participants with events.

SECONDARY outcome

Timeframe: From start date of response to first disease progression, up to 71 weeks.

Population: Patients with Partial Response (PR) or Complete Response (CR) in the evaluable population.

Number of weeks from the time at which measurement criteria are met for Complete Response (CR) or Partial Response (PR) (whichever status is recorded first) until the first date on which recurrence or progressive disease (PD) is objectively documented, taking as reference for PD the smallest measurements recorded since the treatment started, for responders only, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: CR, disappearance of all target lesions; PR, \>=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.

Outcome measures

Outcome measures
Measure	Nera 160 + Pac n=1 Participants Neratinib 160 mg + Paclitaxel 80 mg/m\^2	Nera 240 + Pac n=3 Participants Neratinib 240 mg + Paclitaxel 80 mg/m\^2
Duration of Response	70.1 weeks Insufficient number of participants with events.	33.1 weeks Interval 25.1 to Insufficient number of participants with events.

Adverse Events

Nera 160 + Pac

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Nera 240 + Pac

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Nera 160 + Pac n=3 participants at risk Neratinib 160 mg + Paclitaxel 80 mg/m\^2	Nera 240 + Pac n=7 participants at risk Neratinib 240 mg + Paclitaxel 80 mg/m\^2
Infections and infestations Pneumonia	0.00% 0/3 • From first dose to last dose plus 28 days, up to 78 weeks. Safety Population	14.3% 1/7 • From first dose to last dose plus 28 days, up to 78 weeks. Safety Population

Other adverse events

Additional Information

Senior Director, Clinical Operations

Puma Biotechnology, Inc.

Phone: +1 (424) 248-6500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60