NCT02593708

Brief Summary

Open label, non-randomized, dose escalation and expansion Phase Ia/b trial to evaluate the safety and tolerability of the combination of neratinib plus paclitaxel, trastuzumab and pertuzumab to determine the recommended Phase II/III dose of this combination. Neratinib will be given once daily days 1-21 and should be taken orally with food. Paclitaxel and trastuzumab will be given IV on days 1, 8, and 15 out of 21 day cycles. Pertuzumab will be given IV every 3 weeks on day 1 out of 21-day cycles. Each cycle will be 21 days in duration. Patients will continue on treatment until disease progression or intolerable toxicity.

Trial Health

57
Monitor

Trial Health Score

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

Enrollment
6

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Nov 2015

Geographic Reach
1 country

1 active site

Status
terminated

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

First Submitted

Initial submission to the registry

October 30, 2015

Completed
3 days until next milestone

First Posted

Study publicly available on registry

November 2, 2015

Completed
1 day until next milestone

Study Start

First participant enrolled

November 3, 2015

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 5, 2017

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2017

Completed
Last Updated

November 17, 2017

Status Verified

November 1, 2017

Enrollment Period

1.2 years

First QC Date

October 30, 2015

Last Update Submit

November 13, 2017

Conditions

Solid Tumor

Keywords

HER2+

Outcome Measures

Primary Outcomes (2)

  • Adverse Events

    CTCAE v.4.0

    Up to 2 years

  • Maximum Tolerated Dose

    CTCAE v.4.0

    Up to 2 years

Secondary Outcomes (1)

  • Response Rate

    Up to 2 years

Study Arms (4)

Cohort 0

EXPERIMENTAL

1. Neratinib: 80 mg, daily, oral 2. Paclitaxel: 80 mg/m2, weekly, intravenously 3. Pertuzumab: 840 mg loading dose, 420 mg every 3 weeks, intravenously 4. Trastuzumab: 4 mg/kg loading dose, 2mg/kg every week, intravenously

Drug: NeratinibDrug: PaclitaxelDrug: PertuzumabDrug: Trastuzumab

Cohort 1

EXPERIMENTAL

1. Neratinib: 120 mg, daily, oral 2. Paclitaxel: 80 mg/m2, weekly, intravenously 3. Pertuzumab: 840 mg loading dose, 420 mg every 3 weeks, intravenously 4. Trastuzumab: 4 mg/kg loading dose, 2mg/kg every week, intravenously

Drug: NeratinibDrug: PaclitaxelDrug: PertuzumabDrug: Trastuzumab

Cohort 2

EXPERIMENTAL

1. Neratinib: 160 mg, daily, oral 2. Paclitaxel: 80 mg/m2, weekly, intravenously 3. Pertuzumab: 840 mg loading dose, 420 mg every 3 weeks, intravenously 4. Trastuzumab: 4 mg/kg loading dose, 2mg/kg every week, intravenously

Drug: NeratinibDrug: PaclitaxelDrug: PertuzumabDrug: Trastuzumab

Cohort 3

EXPERIMENTAL

1. Neratinib: 200 mg, daily, oral 2. Paclitaxel: 80 mg/m2, weekly, intravenously 3. Pertuzumab: 840 mg loading dose, 420 mg every 3 weeks, intravenously 4. Trastuzumab: 4 mg/kg loading dose, 2mg/kg every week, intravenously

Drug: NeratinibDrug: PaclitaxelDrug: PertuzumabDrug: Trastuzumab

Interventions

NeratinibDRUG
Cohort 0Cohort 1Cohort 2Cohort 3
PaclitaxelDRUG
Cohort 0Cohort 1Cohort 2Cohort 3
PertuzumabDRUG
Cohort 0Cohort 1Cohort 2Cohort 3
TrastuzumabDRUG
Cohort 0Cohort 1Cohort 2Cohort 3

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Women and men 18 years or older with advanced solid tumor malignancy
  • Ability to understand and voluntarily sign informed consent prior to undergoing any study-related assessments or procedures, as well as adhere to the study visit schedule and other protocol requirements.
  • Local histologic or cytologic confirmation of HER2+ solid tumors by FISH amplification or IHC (3+)
  • Patients must have received one prior approved therapy for metastatic disease and have not curable options
  • For escalation: Documentation by established staging studies or clinical examination to have measurable or non-measurable metastatic disease per RECIST v1.1 criteria.
  • For expansion: Documentation by established staging studies or clinical examination to have measurable metastatic disease per RECIST v1.1 criteria.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  • Adequate organ function:
  • Absolute neutrophil count (ANC) ≥ 1.5 X 109/L
  • Hemoglobin (Hgb) ≥9g/dL
  • Platelets (plt) ≥ 100 x 109/L
  • Potassium within normal range, or correctable with supplements;
  • Serum calcium and magnesium within the normal range (or corrected with supplements)
  • AST and ALT ≤2.5 x Upper Limit Normal (ULN)
  • Serum total bilirubin ≤ 1.5 x ULN
  • +10 more criteria

You may not qualify if:

  • Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
  • Any condition that confounds the ability to interpret data from the study.
  • Patients must have recovered from side effects from prior cancer-directed therapy to grade 1 or less (unless deemed not clinically significant by study investigator).
  • Symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 4 weeks are allowed.
  • Persistent diarrhea or malabsorption ≥ NCI CTCAE grade 1, despite medical management, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function.
  • Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) class III or IV congestive heart failure.
  • Grade 2 or higher neuropathy
  • Known history of: cardiac disease, heart failure or decreased left ventricular ejection fraction, significant clinical arrhythmias
  • Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks, whichever is shorter, prior to starting study drug or who have not recovered from grade 2 or higher side effects of such therapy (except alopecia).
  • Major surgery ≤ 2 weeks prior to starting a study drug or who have not recovered from side effects of such therapy.
  • Known allergic reaction to neratinib, pertuzumab, trastuzumab, paclitaxel, or any of their components.
  • Women who are pregnant or breast-feeding.
  • Known active Human Immunodeficiency Virus (HIV) infection, Hepatitis B or C.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

MeSH Terms

Interventions

neratinibPaclitaxelpertuzumabTrastuzumab

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

October 30, 2015

First Posted

November 2, 2015

Study Start

November 3, 2015

Primary Completion

January 5, 2017

Study Completion

July 31, 2017

Last Updated

November 17, 2017

Record last verified: 2017-11

Locations

US(1)