NCT01423123

Brief Summary

The FB-8 study is designed as an open label, single arm, Phase I dose-escalation study evaluating the combination of weekly paclitaxel with neratinib and trastuzumab in women with metastatic, HER2-positive breast cancer. The primary aim of this study is to determine the safety and tolerability of the three-drug combination.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
21

participants targeted

Target at P25-P50 for phase_1 breast-cancer

Timeline
Completed

Started May 2011

Geographic Reach
1 country

4 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

Study Start

First participant enrolled

May 1, 2011

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

August 19, 2011

Completed
6 days until next milestone

First Posted

Study publicly available on registry

August 25, 2011

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2012

Completed
1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2014

Completed
Last Updated

July 8, 2014

Status Verified

July 1, 2014

Enrollment Period

1.3 years

First QC Date

August 19, 2011

Last Update Submit

July 7, 2014

Conditions

Breast Cancer

Keywords

PaclitaxelTrastuzumabNeratinibBreast CancerHER2-positive

Outcome Measures

Primary Outcomes (1)

  • Safety and tolerability of the three-drug combination

    Number of patients experiencing dose limiting toxicities (DLT).

    Through 6 months after last dose

Secondary Outcomes (2)

  • Overall response rate

    Measured at 24 weeks from start of therapy.

  • Progression-free interval

    Time to disease progression up to 15 months.

Study Arms (1)

Neratinib

EXPERIMENTAL

Paclitaxel (80 mg/m2 IV on days 1, 8, and 15 every 28 days) and trastuzumab (4 mg/kg/ loading dose, then 2 mg/kg) IV weekly beginning on day 1 of paclitaxel, neratinib orally daily beginning on day 1 of paclitaxel until disease progression.

Drug: PaclitaxelBiological: trastuzumabDrug: Neratinib

Interventions

PaclitaxelDRUG

80 mg/m2 IV on days 1, 8, and 15 every 28 days until disease progression.

Neratinib
trastuzumabBIOLOGICAL

4 mg/kg IV loading dose, then 2 mg/kg IV weekly until disease progression.

Neratinib
NeratinibDRUG

Dose level 1: 120 mg/day orally; Dose level 2: 160 mg/day orally; Dose level 3: 240 mg/day orally; Dose level 4: 200 mg/day orally.

Neratinib

Eligibility Criteria

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

You may qualify if:

  • Co-morbid conditions should be taken into consideration, but not the diagnosis of metastatic breast cancer.
  • Patients of reproductive potential must agree to use an effective non-hormonal method of contraception during therapy and for at least 6 months after the last dose of study therapy.
  • The ECOG performance status must be 0, 1, or 2.
  • Patients must have the ability to swallow oral medication.
  • Patients must have histologic or cytologic confirmation of the diagnosis of invasive adenocarcinoma of the breast.
  • There must be documentation that the patient has evidence (measurable or non-measurable) of metastatic breast cancer. Histologic confirmation of metastatic disease is not required.
  • Patients must have ER analysis performed on the primary tumor prior to study entry. If ER analysis is negative, then PgR analysis must also be performed. (Patients are eligible with either hormone receptor-positive or hormone receptor-negative tumors.)
  • Breast cancer must be determined to be HER2-positive prior to study entry. Assays using FISH or CISH require gene amplification. Assays using IHC require a strongly positive (3+) staining score.
  • At the time of study entry, blood counts performed within 4 weeks prior to study entry must meet the following criteria: ANC must be greater than or equal to 1000/mm3; Platelet count must be greater than or equal to 100,000/mm3; Hemoglobin must be greater than or equal to 9 g/dL
  • The following criteria for evidence of adequate hepatic function performed within 4 weeks prior to study entry must be met: total bilirubin must be less than or equal to 1.5 x ULN; AST and ALT must be less than or equal to 2.5 x ULN for the lab or less than or equal to 5 x ULN if liver metastasis
  • Serum creatinine performed within 4 weeks prior to study entry must be less than or equal to 1.5 x ULN for the lab.
  • The LVEF assessment by 2-D echocardiogram or MUGA scan performed within 90 days prior to study entry must be greater than or equal to 50% regardless of the facility's LLN.

You may not qualify if:

  • Previous therapy with neratinib for any malignancy.
  • Symptomatic brain metastases or brain metastases requiring chronic steroids to control symptoms.
  • Active hepatitis B or hepatitis C with abnormal liver function tests.
  • Intrinsic lung disease resulting in dyspnea.
  • Active infection or chronic infection requiring chronic suppressive antibiotics.
  • Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function.
  • Persistent greater than or equal to grade 2 diarrhea regardless of etiology.
  • Sensory or motor neuropathy greater than or equal to grade 2, as defined by the NCI CTCAE v3.0.
  • Conditions that would prohibit intermittent administration of corticosteroids for paclitaxel premedication.
  • Chronic daily treatment with corticosteroids with a dose of greater than or equal to 10 mg/day methylprednisolone equivalent (excluding inhaled steroids).
  • Uncontrolled hypertension defined as a systolic BP greater than 150 mmHg or diastolic BP greater than 90 mmHg, with or without anti-hypertensive medications (Patients with hypertension that is well controlled on medication are eligible.)
  • Cardiac disease (history of and/or active disease) that would preclude the use of any of the drugs included in the treatment regimen. This includes but is not confined to: Active cardiac disease: symptomatic angina pectoris within the past 90 days that required the initiation of or increase in anti-anginal medication or other intervention; ventricular arrhythmias except for benign premature ventricular contractions; supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; conduction abnormality requiring a pacemaker; valvular disease with documented compromise in cardiac function; and symptomatic pericarditis. History of cardiac disease: myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function; history of documented CHF; and documented cardiomyopathy
  • Other nonmalignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow up.
  • Pregnancy or lactation at the time of study entry. (Note: Pregnancy testing should be performed within 14 days prior to study entry according to institutional standards for women of childbearing potential.)
  • The investigator should assess the patient to determine if she has any psychiatric or addictive disorder or other condition that, in the opinion of the investigator, would preclude her from meeting the study requirements.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

NSABP Foundation, Inc.

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232-1305, United States

Location

West Virginia University Hospitals

Morgantown, West Virginia, 26506-9162, United States

Location

Related Publications (1)

  • Jankowitz RC, Abraham J, Tan AR, Limentani SA, Tierno MB, Adamson LM, Buyse M, Wolmark N, Jacobs SA. Safety and efficacy of neratinib in combination with weekly paclitaxel and trastuzumab in women with metastatic HER2-positive breast cancer: an NSABP Foundation Research Program phase I study. Cancer Chemother Pharmacol. 2013 Dec;72(6):1205-12. doi: 10.1007/s00280-013-2262-2.

    PMID: 24077916RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

PaclitaxelTrastuzumabneratinib

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

  • Norman Wolmark, MD

    NSABP Foundation Inc

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 19, 2011

First Posted

August 25, 2011

Study Start

May 1, 2011

Primary Completion

August 1, 2012

Study Completion

March 1, 2014

Last Updated

July 8, 2014

Record last verified: 2014-07

Locations

US(4)