Study Evaluating Neratinib Plus Paclitaxel VS Trastuzumab Plus Paclitaxel In ErbB-2 Positive Advanced Breast Cancer (NEFERTT)

• ClinicalTrials.gov Identifier: NCT00915018
• Recruitment Status: Completed
• First Posted: June 5, 2009
• Results First Posted: November 6, 2017
• Last Update Posted: August 22, 2018
• Sponsor: Puma Biotechnology, Inc.
• Information provided by (Responsible Party): Puma Biotechnology, Inc.

Tracking Information

• First Submitted Date: June 4, 2009
• First Posted Date: June 5, 2009
• Results First Submitted Date: August 10, 2017
• Results First Posted Date: November 6, 2017
• Last Update Posted Date: August 22, 2018
• Actual Study Start Date: August 21, 2009
• Actual Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 6, 2017)

Progression-Free Survival [ Time Frame: From randomization to disease progression or death, assessed up to 5.3 years ]

Defined as the interval from the date of randomization until the first date on which recurrence or progression, or death due to any cause, is documented, censored at the last assessable evaluation or at the initiation of new anticancer therapy.

• Original Primary Outcome Measures (submitted: June 4, 2009): Progression-Free Survival [ Time Frame: 31 months ]

Current Secondary Outcome Measures (submitted: July 25, 2018)

• Objective Response Rate [ Time Frame: From randomization to disease progression or last tumor assessment, assessed up to 5.3 years ]
  Defined as the percentage of subjects who achieved confirmed tumor response (complete or partial response) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-Progressive Disease for non-target lesions, and no new lesions.
• Duration of Response [ Time Frame: From first response to first PD or death, assessed up to 5.3 years after first subject randomized ]
  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, disease progression (PD), or death was objectively documented, taking as a reference for PD the smallest measurements recorded since enrollment, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.
• Clinical Benefit Rate [ Time Frame: From randomization to disease progression or death, assessed up to 5.3 years ]
  Defined as the proportion of patients who achieved overall tumor response (CR or PR) or SD for at least 24 weeks per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
• Symptomatic or Progressive Central Nervous System (CNS) Lesions [ Time Frame: From randomization to disease progression PD or last tumor assessment, assessed up to 5.3 years ]
  Defined as the time interval from the date of randomization until the first date of CNS symptoms, the imaging examination shows CNS progression or is censored at the last assessable evaluation on study or prior to new anti-cancer therapy, if applicable. If median time to Symptomatic or Progressive CNS Lesions is not estimable, cumulative incidence will be reported instead.

• Original Secondary Outcome Measures (submitted: June 4, 2009): Overall Survival [ Time Frame: 44 months ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Evaluating Neratinib Plus Paclitaxel VS Trastuzumab Plus Paclitaxel In ErbB-2 Positive Advanced Breast Cancer
• Official Title: A Randomized, Open-Label, Two-Arm Study Of Neratinib Plus Paclitaxel Versus Trastuzumab Plus Paclitaxel As First-Line Treatment For ErbB-2-Positive Locally Recurrent Or Metastatic Breast Cancer
• Brief Summary: This study is investigating the effects of an experimental drug (neratinib) in combination with paclitaxel versus trastuzumab in combination with paclitaxel for the treatment of women who have not received previous treatment for erbB-2-positive locally recurrent or metastatic breast cancer. The study will compare the effectiveness of each regimen in shrinking tumors and extending the lives of women with erbB-2 (HER2) positive breast cancer. The study will also compare the safety of the two regimens and as well as the quality of life of subjects receiving either regimen.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Drug: Neratinib
  Neratinib - 240 mg orally daily, administered once daily. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
• Drug: Trastuzumab
  Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2mg/kg IV. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
  Other Names:

  • Herceptin
  • Herclon
• Drug: Paclitaxel
  Paclitaxel - 80 mg/m² IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
  Other Names:

  • Taxol
  • Abraxane
  • Onxol
  • Nov-onxol

Study Arms

• Experimental: neratinib plus paclitaxel
  Interventions:

  • Drug: Neratinib
  • Drug: Paclitaxel
• Active Comparator: trastuzumab plus paclitaxel
  Interventions:

  • Drug: Trastuzumab
  • Drug: Paclitaxel

• Publications *: Awada A, Colomer R, Inoue K, Bondarenko I, Badwe RA, Demetriou G, Lee SC, Mehta AO, Kim SB, Bachelot T, Goswami C, Deo S, Bose R, Wong A, Xu F, Yao B, Bryce R, Carey LA. Neratinib Plus Paclitaxel vs Trastuzumab Plus Paclitaxel in Previously Untreated Metastatic ERBB2-Positive Breast Cancer: The NEfERT-T Randomized Clinical Trial. JAMA Oncol. 2016 Dec 1;2(12):1557-1564. doi: 10.1001/jamaoncol.2016.0237.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 6, 2017): 479
• Original Estimated Enrollment (submitted: June 4, 2009): 1200
• Actual Study Completion Date: June 28, 2018
• Actual Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• ErbB-2 positive locally recurrent or metastatic breast cancer
• Eastern Cooperative Oncology Group (ECOG) 0-2
• Measurable disease
• Availability of tumor tissue for HER2 status confirmation

Exclusion Criteria:

• Prior systemic anti-cancer therapy other than endocrine therapy for locally recurrent or metastatic disease
• Prior erbB-2 inhibitor other than trastuzumab or lapatinib in the neoadjuvant or adjuvant setting
• Progression/recurrence within 12 months after completion of adjuvant or neoadjuvant therapy
• History of heart disease
• History of gastrointestinal disease

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Bahamas, Belarus, Belgium, Bulgaria, Canada, China, Croatia, Denmark, France, Germany, Hong Kong, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Malta, Poland, Portugal, Romania, Serbia, Singapore, South Africa, Spain, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Argentina, Brazil, Colombia, Greece, Lebanon, Mexico, Peru, Saudi Arabia

Administrative Information

• NCT Number: NCT00915018
• Other Study ID Numbers: 3144A2-3005 / B1891005
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Puma Biotechnology, Inc.
• Original Responsible Party: Wyeth (Registry Contact: Clinical Trial Registry Specialist), Wyeth
• Current Study Sponsor: Puma Biotechnology, Inc.
• Original Study Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Puma; Biotechnology

• PRS Account: Puma Biotechnology, Inc.
• Verification Date: July 2018