Study Evaluating Safety And Tolerability, Solid Tumor

NCT00768469 | Completed Phase 1 Results DMC

• 1 other identifier: 3144A2-1115 / B1891001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, phase 1 study of ascending multiple oral doses of HKI-272 in combination with paclitaxel.

Conditions

Advanced Malignant Solid Tumors

Keywords

HKI-272; Paclitaxel; Combination; Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity (DLT) - Percentage of Participants With DLT Events

  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.

  From first dose day through day 28.

• Maximum Tolerated Dose

  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.

  From first dose day through day 28.

Secondary Outcomes (3)

• Objective Response Rate

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

• Progression Free Survival

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

• Duration of Response

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

Study Arms (2)

Nera 160 + Pac

EXPERIMENTAL

Neratinib 160 mg + Paclitaxel 80 mg/m\^2

Drug: Neratinib; Drug: Paclitaxel

Nera 240 + Pac

EXPERIMENTAL

Neratinib 240 mg + Paclitaxel 80 mg/m\^2

Drug: Neratinib; Drug: Paclitaxel

Interventions

Neratinib DRUG

Administered orally, continuous, once daily.

Also known as: HKI-272

Nera 160 + Pac; Nera 240 + Pac

Paclitaxel DRUG

Administered IV, on days 1, 8, 15 of 28 day cycle.

Nera 160 + Pac; Nera 240 + Pac

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 · AST and ALT: less than or equal to 2.5 xULN (less than or equal to 5 x ULN if liver metastases are present)
• 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 contraceptives.
• 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.

You may not qualify if:

• Prior treatment with anthracyclines with a cumulative dose of doxorubicin of greater than 400 mg/m\^2, epirubicin dose of greater than 800 mg/m\^2, 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 alopecia).
• 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).

Sponsors & Collaborators

• Puma Biotechnology, Inc.: lead

Study Sites (2)

Investigational Site

Shizuoka, Japan

Location

Investigational Site

Tokyo, Japan

Location

MeSH Terms

Interventions

neratinib; Paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Senior Director, Clinical Operations
• Organization: Puma Biotechnology, Inc.

clinicaltrials@pumabiotechnology.com

+1 (424) 248-6500

Study Officials

• Puma

  Biotechnology

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2008
• First Posted: October 8, 2008
• Study Start: October 1, 2008
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: November 19, 2018
• Results First Posted: November 19, 2018

Record last verified: 2018-04

Locations

JP (2)