Study to Evaluate the Safety and Efficacy of NKTR-102 in Patients With Metastatic or Locally Advanced Breast Cancer

A Multicenter, Open-Label, Phase 2 Study to Evaluate the Safety and Efficacy of NKTR-102 When Given on a Q14 Day or a Q21 Day Schedule in Patients With Metastatic or Locally Advanced Breast Cancer Whose Disease Has Failed Prior Taxane-Based Treatment

This is a multicenter, open-label, two-arm, 2-stage, Phase 2 study of NKTR-102 in patients with metastatic or locally advanced breast cancer whose disease has failed prior taxane-based treatment in the metastatic setting.

Patients will be randomized 1:1 into one of two treatment arms. NKTR 102 will be administered at a dose level of 145 mg/m2 in both arms. In Arm A, NKTR-102 will be given on a q14d schedule. In Arm B, NKTR-102 will be given on a q21d schedule. Approximately 70 patients may be evaluated in this study with approximately 35 patients enrolled in each treatment arm.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Tumor
• Intervention / Treatment: Drug: NKTR-102; Drug: NKTR-102

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 2-2-541-72-26
    • Institut Jules Bordet
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Gent, Belgium, 9000
    • De Pintelaan 1885
  • Liege, Belgium, 4000
    • CHU de Liège
  • Wilrijk, Belgium, 2610
    • Gasthuiszusters Antwerpen
• United Kingdom
  • Bebington, United Kingdom, CH63 3J7
    • Clatterbridge Centre for Oncology
  • Cardiff, United Kingdom, CH14 2TL
    • Velindre Hospital
  • Glasgow, United Kingdom, G12 ONY
    • Beatson Oncology Center
  • Leed, United Kingdom, LS97TF
    • St James University Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital
  • Sheffield, United Kingdom, S10 2SJ
    • Weston Park Hospital
• United States
  • California
    • Los Angeles, California, United States, 90089-9177
      • USC Norris Comprehensive Cancer Center
    • Rancho Mirage, California, United States, 92270
      • Desert Hematology Oncology Medical Group
    • Stockton, California, United States, 95204
      • Stockton Hematology/Oncology
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Louisville Oncology Clinical Research Program
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Rhode Island
    • East Providence, Rhode Island, United States, 02915
      • Pharma Resource
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Inoperable metastatic or locally advanced breast cancer
2. No more than 2 prior chemotherapy regimens given in a metastatic or locally advanced setting and prior treatment in the metastatic setting must have included a taxane

Exclusion Criteria:

1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to Day 1 of Cycle 1
2. Patients who have had any major surgery within 4 weeks prior to Day 1 of Cycle or minor surgery within 2 weeks prior to Day 1 of Cycle 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NKTR-102 q14d; NKTR-102	Drug: NKTR-102; NKTR-102 given on a q14 day schedule; Drug: NKTR-102; NKTR-102 given on a q21 day schedule
Experimental: NKTR-102 q21d; NKTR-102	Drug: NKTR-102; NKTR-102 given on a q14 day schedule; Drug: NKTR-102; NKTR-102 given on a q21 day schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Per Response Evaluation Criteria In Solid Tumors (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kaplan Meier Estimate of Progression-Free Survival (PFS)	Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions", or similar definition as accurate and appropriate.	Up to 2 years.
Kaplan Meier Estimate of Overall Survival (OS)	OS was calculated as the time from the date of first study drug administration until death from any cause. Subjects alive at the time of analysis were censored at the time they were last known alive. OS was analyzed for the ITT population.	Up to 2 years.
Kaplan Meier Estimate of 6-month Survival	Six-month survival (i.e., overall survival proportion at 6 months) was estimated using Kaplan Meier method. The analyses were performed in the ITT population.	From Cycle 1 Day 1 to the end of 6 months.
Kaplan Meier Estimate of 1-year Survival	One year survival (i.e., overall survival proportion at 12 months) was estimated using Kaplan Meier method. The analyses were performed in the ITT population.	From Cycle 1 Day 1 to the end of 12 months.
Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group	An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. TEAE was any event not present before exposure to the study drug or any event already present that worsened in either intensity or frequency after exposure to the study drug. All AEs were assessed for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0. If a particular AE was not listed in the NCI CTCAE Version 3.0, the following criteria were used: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life threatening or disabling; Grade 5 = Death.	Up to 2 years.

Collaborators and Investigators

• Sponsor: Nektar Therapeutics

Publications and helpful links

General Publications

• Awada A, Garcia AA, Chan S, Jerusalem GH, Coleman RE, Huizing MT, Mehdi A, O'Reilly SM, Hamm JT, Barrett-Lee PJ, Cocquyt V, Sideras K, Young DE, Zhao C, Chia YL, Hoch U, Hannah AL, Perez EA; NKTR-102 Study Group. Two schedules of etirinotecan pegol (NKTR-102) in patients with previously treated metastatic breast cancer: a randomised phase 2 study. Lancet Oncol. 2013 Nov;14(12):1216-25. doi: 10.1016/S1470-2045(13)70429-7. Epub 2013 Oct 4.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: December 4, 2008
• First Submitted That Met QC Criteria: December 4, 2008
• First Posted (Estimate): December 5, 2008

Study Record Updates

• Last Update Posted (Actual): July 9, 2018
• Last Update Submitted That Met QC Criteria: June 7, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etirinotecan pegol
• Other Study ID Numbers: 08-PIR-05