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Study Evaluating Neratinib In Combination With Vinorelbine In Subjects With Advanced Or Metastatic Solid Tumors

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ClinicalTrials.gov Identifier: NCT00958724
Recruitment Status : Completed
First Posted : August 13, 2009
Results First Posted : February 26, 2018
Last Update Posted : February 26, 2018
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.

Brief Summary:
The purposes of this study are to evaluate the safety and tolerability of neratinib in combination with vinorelbine at the maximum tolerated dose (MTD) determined in a previous study, or to determine a lower MTD of the two drugs, as well as to obtain preliminary information on whether the combination of the two drugs has any effect on solid tumors in Japanese patients.

Condition or disease Intervention/treatment Phase
Advanced Malignant Solid Tumors Drug: Neratinib Drug: Vinorelbine Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study Of Neratinib (HKI-272) In Combination With Vinorelbine In Japanese Subjects With Advanced Or Metastatic Solid Tumors
Actual Study Start Date : July 2009
Actual Primary Completion Date : April 2010
Actual Study Completion Date : April 2010

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Neratinib and Vinorelbine
Neratinib: 240 mg administered daily by mouth continuously, Vinorelbine: 25 mg/m^2 administered IV on Day 1 and 8 of 21 day cycle
Drug: Neratinib
Other Names:
  • HKI-272
  • Nerlynx

Drug: Vinorelbine



Primary Outcome Measures :
  1. DLT of Neratinib in Combination With Vinorelbine [ Time Frame: From first dose date to 21st day ]
    Incidence of DLT of neratinib in combination with vinorelbine in Japanese patients


Secondary Outcome Measures :
  1. Best Overall Response [ Time Frame: From first dose date to progression or last tumor assessment ]
    Best Overall Response in Evaluable Population.

  2. Duration of Objective Response [ Time Frame: From first response date to PD/death ]
    The duration of objective response was measured from the time at which measurement criteria were met for CR or PR (whichever status was recorded first) until the first date on which recurrence or PD was objectively documented, taking as reference for PD the smallest measurements recorded since the treatment started.

  3. Objective Response Rate [ Time Frame: From first dose date to progression or last tumor assessment ]
    The Objective Response Rate (ORR) was defined as the proportion of subjects who achieved complete response (CR) or partial response (PR).

  4. PFS, in Weeks [ Time Frame: From first dose to last evaluation ]
    The interval from the date of the first dose of test article until the first date on which recurrence or progression, or death due to any cause, was documented, censored at the last evaluation.

  5. AUC Tau of Neratinib in Combination With Vinorelbine [ Time Frame: Predose, and hour 1, 2, 4, 6, 8 and 24 on day 8. ]
    AUC of Neratinib at day 8 following Administration of Neratinib 240 mg in combination with Vinorelbine 25 mg/m^2 to Japanese Subjects with Cancer.

  6. t 1/2 of Neratinib in Combination With Vinorelbine [ Time Frame: Predose, and hour 1, 2, 4, 6, 8 and 24 on day 8. ]
    Terminal-phase elimination half-life of Neratinib at day 8 following Administration of Neratinib 240 mg in combination with Vinorelbine 25 mg/m^2 to Japanese Subjects with Cancer.



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed pathologic diagnosis of a solid tumor that is not curable with available therapies for which neratinib plus vinorelbine is a reasonable treatment option.
  • At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors.
  • Eastern Cooperative Oncology Group performance status of 0 to 2 (not declining within 2 weeks before signing the informed consent form).
  • Recovery from all clinically significant AEs related to prior therapies (excluding alopecia).
  • Left ventricular ejection fraction within the study site's limits of normal.
  • Screening laboratory values within the following parameters:

    • Absolute neutrophil count: 1.5 × 109/L
    • Platelet count: 100 × 109/L
    • Hemoglobin: 9.0 g/dL
    • Serum creatinine: 1.5 × upper limit of normal
    • Total bilirubin: 1.5 × ULN
    • Aspartate aminotransferase and alanine aminotransferase: 2.5 × ULN (<= 5 × ULN if liver metastases are present).
  • For women of childbearing potential, a negative urine or serum pregnancy test result before study entry.
  • All female and male subjects who are biologically capable of having children 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. A subject is biologically capable of having children if he or she is using contraceptives or if his or her sexual partner is sterile or using contraceptives.

Exclusion Criteria:

  • Prior treatment with anthracyclines with a cumulative dose of doxorubicin of >400 mg/m2, or of epirubicin >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 at least 2 weeks before treatment day 1.
  • Bone as the only site of disease.
  • Active central nervous system 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 are off anticonvulsants and steroids for at least 4 weeks before cycle 1 day 1) .
  • QT (QTc) interval > 0.47 s or a known history of QTc prolongation or Torsades de Pointes.
  • Presence of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association functional classification of =2), angina requiring treatment, myocardial infarction within the past 12 months, or any clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention.
  • Pregnant or breastfeeding women. Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn disease, malabsorption, or grade 2 diarrhea of any etiology at baseline).
  • Inability or unwillingness to swallow tablets (neratinib).
  • Preexisting grade 2 or greater motor or sensory neuropathy.
  • Subject known to be human immunodeficiency virus seropositive and/or have acute or chronic hepatitis B infection (hepatitis B surface antigen [HBsAg] positive) or hepatitis C infection (anti-HCV positive).
  • History of known hypersensitivity to vinorelbine and any of its components.
  • 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.
  • Clinically significant ongoing or recent infection within 2 weeks before treatment day 1.
  • 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) or uncontrolled major seizure.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00958724


Locations
Japan
Shizuoka Cancer Center
Shizuoka, Japan, 411-8777
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Tokyo, Japan, 135-8550
Sponsors and Collaborators
Puma Biotechnology, Inc.
Investigators
Study Director: Puma Biotechnology

Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT00958724     History of Changes
Other Study ID Numbers: 3144A2-1118
B1891002
First Posted: August 13, 2009    Key Record Dates
Results First Posted: February 26, 2018
Last Update Posted: February 26, 2018
Last Verified: August 2017

Keywords provided by Puma Biotechnology, Inc.:
HKI-272
Vinorelbine
Combination
Solid Tumor
Neratinib
Nerlynx
PB-272

Additional relevant MeSH terms:
Vinorelbine
Vinblastine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action