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Neratinib With and Without Temsirolimus for Patients With HER2 Activating Mutations in Non-Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01827267
First Posted: April 9, 2013
Last Update Posted: September 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Puma Biotechnology, Inc.
April 1, 2013
April 9, 2013
August 8, 2017
September 11, 2017
September 11, 2017
July 1, 2013
September 20, 2016   (Final data collection date for primary outcome measure)
Objective Response Rate (ORR) [ Time Frame: From randomization to disease progression or last tumor assessment ]
ORR is defined as proportion of subjects who achieved confirmed complete response (CR) or partial response (PR) per RECIST v1.1. A complete or partial response must be confirmed no less than 4-weeks after the criteria for response are initially met.
Overall Response Rate (ORR) [ Time Frame: minimum 21 days ]
ORR is defined as Complete Response (CR) and Partial Response (PR) after receiving at least one prior regimen of chemotherapy
Complete list of historical versions of study NCT01827267 on ClinicalTrials.gov Archive Site
  • Clinical Benefit Rate (CBR) [ Time Frame: From randomization to disease progression or death ]
    CBR is defined as the proportion of patients who achieved objective response (CR or PR) or SD for at least 12 weeks.
  • Duration of Response (DOR) [ Time Frame: From first response to first PD or death ]
    Measured from the time at which measurement criteria were first met for CR or PR (whichever status was recorded first), until the date of first recurrence, PD, or death was objectively documented, taking as a reference for PD the smallest measurements recorded since enrollment, per RECIST (v1.1) criteria.
  • Progression Free Survival (PFS) [ Time Frame: From randomization to disease progression or last tumor assessment ]
    Defined as time from date of randomization until the first disease recurrence or progression per RECIST V1.1 or death due to any cause; censored at the last assessable evaluation or at the initiation of new anti-cancer therapy. Disease assessment is based on investigator tumor assessments. If no post-baseline tumor assessment then censored at enrollment date.
  • Overall Survival (OS) [ Time Frame: From randomization to death or end of long term follow-up ]
    Defined as the time (month) from randomization to death due to any cause; censored at the date last known alive.
  • Clinical Benefit Rate (CBR) [ Time Frame: at least 12 weeks ]
    CBR is defined as the percentage of patients with CR plus PR plus Stable Disease (SD)
  • Duration of Response (DOR) [ Time Frame: Estimated 6 months ]
    DOR is defined as the date when criterion of CR or PR is first met and subsequently confirmed (whichever status is recorded first) to the first date of documented disease progression
  • Progression Free Survival (PFS) [ Time Frame: Estimated 6 months ]
  • Overall Survival (OS) [ Time Frame: Estimated 12 months ]
  • Safety (Adverse Events [AEs] and Serious Adverse Events [SAEs]) [ Time Frame: Estimated 6 months ]
  • Change from baseline in quality of life measured using EQ-5D-5L and FACT-L [ Time Frame: Estimated 6 months ]
    Validated Quality of Life Questionnaires
Not Provided
Not Provided
 
Neratinib With and Without Temsirolimus for Patients With HER2 Activating Mutations in Non-Small Cell Lung Cancer
A Phase 2 Study of Neratinib and Neratinib Plus Temsirolimus in Patients With Non-Small Cell Lung Cancer Carrying Known HER2 Activating Mutations
This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter, multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus combination therapy in patients with non-small cell lung cancer (NSCLC) who have documented somatic HER2 mutations.

This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter, multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus combination therapy in patients with NSCLC and documented somatic HER2 mutations. Patients randomized at study entry into 1 of 2 treatment arms:

  • Arm A: neratinib 240 mg orally once daily
  • Arm B: neratinib 240 mg orally once daily plus temsirolimus 8 mg once weekly by intravenous (IV) infusion

In the case of disease progression, patients initially assigned to neratinib monotherapy arm given option to add temsirolimus 8 mg IV once weekly.

Patients on combination therapy given option to dose-escalate temsirolimus to 15 mg/week at the end of first cycle of treatment, if well tolerated and at the physician's discretion. If neratinib 240 mg/day plus temsirolimus 15 mg/week dose not well tolerated, patient subsequently dose reduced back to neratinib 240 mg/day plus temsirolimus 8 mg/week.

Dosing continuous on nominal 3-week cycles until evidence of progressive disease, unacceptable toxicity, or patient withdrawal of consent.

Disease measured radiographically at baseline and every 6 weeks until disease progression or withdrawal from the study.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
HER2-mutant Non-Small Cell Lung Cancer
  • Drug: neratinib
    Other Name: Nerlynx
  • Drug: temsirolimus
    Other Name: Torisel
  • Experimental: neratinib monotherapy
    240 mg once daily with food, continuously in 21 day cycles
    Intervention: Drug: neratinib
  • Experimental: neratinib plus temsirolimus
    240 mg neratinib plus 8 mg temsirolimus IV with optional dose escalation to 15 mg temsirolimus
    Interventions:
    • Drug: neratinib
    • Drug: temsirolimus
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
62
December 2017
September 20, 2016   (Final data collection date for primary outcome measure)

Inclusion Criteria

  1. Aged ≥18 years at the time of signing the informed consent.
  2. Histologically confirmed diagnosis of NSCLC, advanced (stage IIIB) or metastatic (stage IV).
  3. Documented somatic ErbB2 (HER2) activating mutation.
  4. Patients with anaplastic lymphoma kinase (ALK) translocations must have received crizotinib, except for cases of intolerable toxicity to crizotinib.
  5. At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
  6. Eastern Cooperative Oncology Group (ECOG) status <2.
  7. Left ventricular ejection fraction (LVEF) ≥50% measured by multiple -gated acquisition scan (MUGA) or echocardiogram (ECHO).
  8. Negative β-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after menopause.
  9. Men and women of childbearing potential must agree and commit to the use of a highly effective method of contraception, as determined to be acceptable by the Investigator, from the time of informed consent until 3 months after the last dose of the investigational products.
  10. Provide written, informed consent to participate in the study and follow the study procedures.

Exclusion Criteria

  1. Previous treatment with any investigational agent ≤14 days prior to the initiation of investigational products.
  2. Previous treatment with any strong inhibitor and/or inducer of CYP3A4 enzyme or sensitive P-glycoprotein (P-gp) substrates ≤30 days prior to the initiation of investigational products.
  3. Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ≥2), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia.
  4. Major surgery <30 days of starting treatment.
  5. Chronic steroid use (prednisone >12.5 mg/day or dexamethasone >2 mg/day, excluding inhaled steroids).
  6. Currently breast feeding.
  7. Symptomatic or unstable brain metastases.
  8. QTc interval >0.450 seconds for men and >0.470 seconds for women, or known history of QTc prolongation or Torsades de Pointes (TdP).
  9. Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events Version 4.0 [CTCAE v.4.0] diarrhea of any etiology at baseline).
  10. Prior exposure to neratinib or mTOR inhibitor.
  11. Active infection or unexplained fever >38.5°C (101.3°F).
  12. Unable or unwilling to swallow tablets.
  13. Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that would, in the Investigator's judgment, make the patient inappropriate for this study.
  14. Known hypersensitivity to any component of the investigational products.
  15. Unstable or uncontrolled diabetes mellitus (glycosylated hemoglobin [HbA1c] >6.5%).
  16. Screening laboratory assessments outside the following limits: ANC <1000/μL (<1.0 x 109/L), Platelet count <75,000/μL (<75 x 109/L), Hemoglobin <8 g/dL, transfusions allowed, must be at least 7 days prior to baseline, Total bilirubin >1.5 x institutional upper limit of normal (ULN), AST and/or ALT 5 minutes, Creatinine clearance <50 mL/min.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
France,   United States
 
 
NCT01827267
PUMA-NER-4201
2012-004743-68 ( EudraCT Number )
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Puma Biotechnology, Inc.
Puma Biotechnology, Inc.
Not Provided
Not Provided
Puma Biotechnology, Inc.
August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP