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A Phase 1 Study Of Neratinib (HKI-272) In Combination With Paclitaxel In Subjects With Solid Tumors

Phase 1
20 Years
Not Enrolling
Advanced Malignant Solid Tumors

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Trial Information

A Phase 1 Study Of Neratinib (HKI-272) In Combination With Paclitaxel In Subjects With Solid Tumors

Inclusion Criteria:

- Subjects must have confirmed pathologic diagnosis of a solid tumor that is not
curable with available therapy for which HKI-272 plus paclitaxel is a reasonable
treatment option.

- At least 1 measurable lesion as defined by RECIST criteria.

- Eastern Cooperative Oncology Group (ECOG) 0 to 1

- LVEF within institutional limits of normal (by MUGA or ECHO).

- Screening laboratory values within the following parameters:

- ANC: greater than or equal to 1.5 x 10E9 /L (1,500 /mm3)

- Platelet count: 10 x 10E10 /L (100,000 /mm3)

- Hemoglobin: greater than or equal to 9.0 g/dL

- Serum creatinine: less than or equal to 1.5 x upper limit of normal (ULN)

- Total bilirubin: less than or equal to 1.5 xULN ยท AST and ALT: less than or
equal to 2.5 xULN (less than or equal to 5 x ULN if liver metastases are

- For women of child bearing potential, a negative urine or serum pregnancy test result
before study entry. A woman of childbearing potential is one who is biologically
capable of becoming pregnant. This includes women who are using contraceptives or
other means of birth control or whose sexual partners are either sterile or using

- All subjects who are not surgically sterile or postmenopausal must agree and commit
to the use of a reliable method of birth control for the duration of the study and
for 28 days after the last dose of test article.

Exclusion Criteria:

- Prior treatment with anthracyclines with a cumulative dose of doxorubicin of greater
than 400 mg/m2, epirubicin dose of greater than 800 mg/m2, or the equivalent dose for
other anthracyclines or derivatives.

- Major surgery, chemotherapy, radical (curative intent) radiotherapy, investigational
agents, or other cancer therapy within 2 weeks of treatment day 1 or non-recovery
from all clinically significant acute adverse effects of prior therapies (excluding

- Subjects with bone or skin as the only site of disease.

- Active central nervous system (CNS) metastases, as indicated by clinical symptoms,
cerebral edema, and/or progressive growth (subjects with a history of CNS metastases
or cord compression are allowable if they have been definitively treated and have
been clinically stable for at least three months, and off steroids or
anticonvulsants, before first dose of test article).

- QTc interval greater than 0.47 second or known history of QTc prolongation or Torsade
de Pointes (TdP).

- Known hypersensitivity to paclitaxel or Cremophor EL (polyoxyethylated castor oil).

- Pregnant or breast feeding women.

- Significant chronic or recent acute gastrointestinal disorder with diarrhea as a
major symptom (e.g., Crohn's disease, malabsorption, or Grade greater than or equal
to 2 diarrhea of any etiology at baseline).

- Inability or unwillingness to swallow the HKI-272.

- Treatment with a taxane within 3 months of treatment day 1.

- Pre-existing grade 2 or greater motor or sensory neuropathy.

- Any other cancer within 5 years prior to screening with the exception of
contralateral breast carcinoma, adequately treated cervical carcinoma in situ, or
adequately treated basal or squamous cell carcinoma of the skin.

- Presence of clinically significant or uncontrolled cardiac disease, including
congestive heart failure (New York Heart Association [NYHA] functional classification
of greater than or equal to 2), angina requiring treatment, myocardial infarction
within the past 12 months, or any clinically significant supraventricular arrhythmia
or ventricular arrhythmia requiring treatment or intervention.

- Evidence of significant medical illness or abnormal laboratory finding that would, in
the investigator's judgment, make the subject inappropriate for this study. Examples
include, but are not limited to, serious active infection (ie, requiring intravenous
antibiotic or antiviral agent), uncontrolled major seizure disorder, or significant
pulmonary disorder (e.g. interstitial pneumonitis, pulmonary hypertension).

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The primary objectives are to assess the safety and tolerability, and to decide the recommended dose of HKI-272 in combination with paclitaxel in subjects with advanced solid tumors.

Outcome Time Frame:

19 months

Safety Issue:


Principal Investigator


Investigator Role:

Study Director

Investigator Affiliation:



Japan: Ministry of Health, Labor and Welfare

Study ID:




Start Date:

October 2008

Completion Date:

January 2011

Related Keywords:

  • Advanced Malignant Solid Tumors
  • HKI-272
  • Paclitaxel
  • Combination
  • Solid Tumor
  • Neoplasms