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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02915744




Registration number
NCT02915744
Ethics application status
Date submitted
22/09/2016
Date registered
27/09/2016
Date last updated
6/03/2019

Titles & IDs
Public title
A Study of Etirinotecan Pegol (NKTR-102) Versus Treatment of Physician's Choice (TPC) in Patients With Metastatic Breast Cancer Who Have Stable Brain Metastases and Have Been Previously Treated With an Anthracycline, a Taxane, and Capecitabine
Scientific title
A Phase 3 Open-Label, Randomized, Multicenter Study of NKTR-102 Versus Treatment of Physician's Choice (TPC) in Patients With Metastatic Breast Cancer Who Have Stable Brain Metastases and Have Been Previously Treated With an Anthracycline, a Taxane, and Capecitabine
Secondary ID [1] 0 0
15-102-14
Universal Trial Number (UTN)
Trial acronym
ATTAIN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastasis 0 0
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NKTR-102
Treatment: Drugs - Eribulin
Treatment: Drugs - Ixabepilone
Treatment: Drugs - Vinorelbine
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Docetaxel
Treatment: Drugs - Nab-paclitaxel

Experimental: NKTR-102 - In Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle.

Active Comparator: Treatment of Physician's Choice (TPC) - In Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.


Treatment: Drugs: NKTR-102


Treatment: Drugs: Eribulin


Treatment: Drugs: Ixabepilone


Treatment: Drugs: Vinorelbine


Treatment: Drugs: Gemcitabine


Treatment: Drugs: Paclitaxel


Treatment: Drugs: Docetaxel


Treatment: Drugs: Nab-paclitaxel


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) of Patients - To compare Overall Survival (OS) of patients who receive 145 mg/m2 NKTR-102 given once every 21 days (q21d) with OS of patients who receive Treatment of Physician's Choice (TPC). Overall survival is defined as the time from the date of randomization to the date of death from any cause. Patients will be followed until their date of death or until final database closure. Patients who are lost-to-follow-up or are alive at the time of analysis will be censored at the time they were last known to be alive or at the date of event cut-off for OS analysis.
Timepoint [1] 0 0
Within 3 years from study start
Secondary outcome [1] 0 0
Progression-Free Survival (Outside the Central Nervous System) - Progression-Free Survival (PFS) is defined as the time from the date of randomization to the earliest evidence of documented Progressive Disease (PD) or of death from any cause. The date of global deterioration or symptomatic deterioration will not be used as the date of PD.
Timepoint [1] 0 0
Through study completion, an expected average of 1 year
Secondary outcome [2] 0 0
Progression-Free Survival in Brain Metastasis (PFS-BM) - Progression-Free Survival in Brain Metastasis (PFS-BM) is defined as the time from the date of randomization to the earliest evidence of documented Progressive Disease (PD) per Response Assessment in Neuro-Oncology—Brain Metastases (RANO-BM) in brain metastases or death from any cause. The PD will also be determined by the investigator's assessments.
Timepoint [2] 0 0
Through study completion, an expected average of 1 year
Secondary outcome [3] 0 0
Progression-Free Survival (Overall) - Progression-free survival (CNS and peripheral) is defined as the time from the date of randomization to the earliest evidence of documented PD in either the CNS or peripheral (using RANO-BM) or death from any cause. The PD will be determined by both the investigator's and the central imaging facility assessments. The same statistical methods that were used for PFS and PFS-BM will be used for PFS (Overall).
Timepoint [3] 0 0
Through study completion, an expected average of 1 year
Secondary outcome [4] 0 0
Objective Response Rates (ORR) of the NKTR-102 Treatment and the Treatment of Physician's Choice (TPC) - Objective Response Rate (ORR) will be defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR) (RECIST for lesions outside the Central Nervous System (CNS); RANO-BM for CNS lesions) based upon the best response as assessed by the central imaging facility. As a secondary analysis, ORR will be calculated based on the Investigator assessment of response.
Timepoint [4] 0 0
Through study completion, an expected average of 1 year
Secondary outcome [5] 0 0
Clinical Benefit Rate (CBR) - Clinical Benefit Rate will be defined as the proportion of patients having a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for at least 4 months (= 120 days). The SD duration of 4 months is selected to reflect the shorter life expectancy of study population. CBR will be calculated based on both the central imaging facility assessment of response, progression and stability of disease, as well as the investigator's assessment of these parameters.
Timepoint [5] 0 0
For at least 4 months, with an expected average of 1 year
Secondary outcome [6] 0 0
Duration of Response (DoR) - Duration of response (DoR) outside the CNS will be defined as the time from first documented CR or PR until the earliest evidence of disease progression per RECIST v1.1 or death from any cause. DoR will be calculated based on the central imaging facility assessment of response and progression as well as the investigator's assessment of response and progression.
Timepoint [6] 0 0
Through study completion, an expected average of 1 year
Secondary outcome [7] 0 0
WBRT - To compare the incidence and cumulative frequency of WBRT after date of randomization by treatment group. The protocol will also compare time-to-WBRT (defined as the date of first whole-brain radiation fraction) in those patients who received WBRT after the date of randomization by treatment group.
Timepoint [7] 0 0
Through study completion, an expected average of 1 year
Secondary outcome [8] 0 0
Compare Health-Related Quality of Life (HRQoL) using the European Organisation for Treatment of Cancer (EORTC) Quality of Life Core 30 (QLQ-C30) module with the brain neoplasms 20-question (BN-20) subscale.
Timepoint [8] 0 0
Through study completion, an expected average of 1 year
Secondary outcome [9] 0 0
Compare Health-Related Quality of Life (HRQoL) using the the EuroQoL 5D (EQ-5D-5L™)
Timepoint [9] 0 0
Through study completion, an expected average of 1 year
Secondary outcome [10] 0 0
Compare Health-Related Quality of Life (HRQoL) using the Brief Fatigue Inventory (BFI)
Timepoint [10] 0 0
Through study completion, an expected average of 1 year
Secondary outcome [11] 0 0
Magnitude of Clinical Benefit - The magnitude of clinical benefit of NKTR-102 will be assessed by the European Society for Medical Oncology magnitude of clinical benefit scale (ESMO-MCBS) (v1.0).
Timepoint [11] 0 0
Through study completion, an expected average of 1 year
Secondary outcome [12] 0 0
Maximum observed serum concentration (Cmax) of NKTR-102
Timepoint [12] 0 0
Through study completion, an expected average of 1 year
Secondary outcome [13] 0 0
Time of maximum observed serum concentration (Tmax) of NKTR-102
Timepoint [13] 0 0
Through study completion, an expected average of 1 year
Secondary outcome [14] 0 0
Area Under the serum Concentration time curve in the dosing interval (AUCtau) of NKTR-102
Timepoint [14] 0 0
Through study completion, an expected average of 1 year
Secondary outcome [15] 0 0
Half-life of (t1/2) of NKTR-102
Timepoint [15] 0 0
Through study completion, an expected average of 1 year
Secondary outcome [16] 0 0
Number of participants with adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3
Timepoint [16] 0 0
Through study completion, an expected average of 1 year

Eligibility
Key inclusion criteria
- Female or male, age = 18 years.

- Histologically-confirmed carcinoma of the breast (either the primary or metastatic
lesions) for whom single-agent cytotoxic chemotherapy is indicated. Patients may have
either measurable or non-measurable disease according to RECIST version 1.1.

- Patients must have a history of brain metastases that are non-progressing.

- For triple-negative breast cancer, a minimum of 1 prior cytotoxic chemotherapy regimen
must have been administered for the indication of metastatic disease.Depending on
receptor status, 1 or 2 prior cytotoxic regimens are required prior to enrollment in
this trial; hormonal and/or human epidermal growth factor receptor 2 (HER2) -targeted
agents may be required.

- Have had prior therapy (administered in the neoadjuvant, adjuvant, and/or metastatic
setting) with an anthracycline, a taxane, and capecitabine (prior anthracycline can be
omitted if not medically appropriate or contraindicated for the patient).

- Last dose of anticancer therapy must have been administered within 6 months of the
date of randomization into this study.

- All anticancer- and radiation therapy-related toxicities must be completely resolved
or downgraded to Grade 1 or less (neuropathy may be Grade 2 or less).

- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Demonstrate adequate organ function obtained within 14 days prior to randomization and
analyzed by the central laboratory.

- Women of childbearing potential (WCBP) must agree to use highly effective methods of
birth control throughout the duration of the study until 6 months following the last
dose of study drug.

- Males with female partners of child-bearing potential must agree to use a barrier
contraception (e.g., condom with spermicidal foam/gel/film/cream/suppository)
throughout the duration of the study until 6 months following the last dose of study
drug; in addition to their female partner using either an intrauterine device or
hormonal contraception and continuing until 6 months following the last dose of study
drug. Male patients should not donate sperm until 6 months following the last dose of
study drug.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Last dose of anticancer therapy (including HER2-targeted therapy) within 14 days prior
to randomization.

- High-dose chemotherapy followed by stem cell transplantation (autologous or
allogeneic).

- Major surgery within 28 days prior to randomization.

- Concomitant use of any anticancer therapy or use of any investigational agent(s).

- Received prior treatment for cancer with a camptothecin-derived agent.

- Lesions on imaging, by cerebrospinal fluid or with neurological findings that are
consistent with leptomeningeal disease or meningeal carcinomatosis.

- Chronic or acute GI disorders resulting in diarrhea of any severity grade.

- Patients who are pregnant or lactating, plan to get pregnant, or have a positive serum
pregnancy test prior to randomization.

- Enzyme-inducing anti-epileptic drugs (EIAEDs) within 14 days of randomization.

- Hepatitis B or C, tuberculosis, or HIV.

- Cirrhosis.

- Prior malignancy (other than breast cancer) unless diagnosed and definitively treated
more than 5 years prior to randomization.

- Daily use of oxygen supplementation.

- Significant known cardiovascular impairment.

- Prior treatment with NKTR-102.

- Psychiatric illness, social situation, or geographical situation that preclude
informed consent or limit compliance.

- Known intolerance or hypersensitivity to any of the products used in this study or
their excipients.

- For patients selecting vinorelbine or gemcitabine as the TPC agent, patients may not
receive yellow fever vaccine in the 28 days prior to randomization.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Investigatory Site - Albury - Albury
Recruitment hospital [2] 0 0
Investigator Site - Darlinghurst - Darlinghurst
Recruitment hospital [3] 0 0
Investigator Site - Wollongong - Wollongong
Recruitment hospital [4] 0 0
Investigator Site - Brisbane - Brisbane
Recruitment hospital [5] 0 0
Investigator Site - Subiaco - Subiaco
Recruitment hospital [6] 0 0
Investigator Site - Box Hill - Box Hill
Recruitment hospital [7] 0 0
Investigator Site - Nedlands - Nedlands
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2500 - Wollongong
Recruitment postcode(s) [4] 0 0
4101 - Brisbane
Recruitment postcode(s) [5] 0 0
6008 - Subiaco
Recruitment postcode(s) [6] 0 0
3128 - Box Hill
Recruitment postcode(s) [7] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Utah
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
Belgium
State/province [16] 0 0
Brussels
Country [17] 0 0
Belgium
State/province [17] 0 0
Charleroi
Country [18] 0 0
Belgium
State/province [18] 0 0
Edegem
Country [19] 0 0
Belgium
State/province [19] 0 0
Liège
Country [20] 0 0
Belgium
State/province [20] 0 0
Namur
Country [21] 0 0
Belgium
State/province [21] 0 0
Sint-Niklaas
Country [22] 0 0
Belgium
State/province [22] 0 0
Woluwe-Saint-Lambert
Country [23] 0 0
Canada
State/province [23] 0 0
Quebec
Country [24] 0 0
Czechia
State/province [24] 0 0
Praha
Country [25] 0 0
France
State/province [25] 0 0
Grenoble
Country [26] 0 0
France
State/province [26] 0 0
Le Mans
Country [27] 0 0
France
State/province [27] 0 0
Nîmes
Country [28] 0 0
France
State/province [28] 0 0
Paris
Country [29] 0 0
France
State/province [29] 0 0
Rennes
Country [30] 0 0
France
State/province [30] 0 0
Rouen
Country [31] 0 0
France
State/province [31] 0 0
Saint-Cloud
Country [32] 0 0
France
State/province [32] 0 0
Strasbourg
Country [33] 0 0
France
State/province [33] 0 0
Toulouse
Country [34] 0 0
Israel
State/province [34] 0 0
Be'er Ya'aqov
Country [35] 0 0
Israel
State/province [35] 0 0
Beersheba
Country [36] 0 0
Israel
State/province [36] 0 0
Haifa
Country [37] 0 0
Israel
State/province [37] 0 0
Jerusalem
Country [38] 0 0
Israel
State/province [38] 0 0
Tel Aviv
Country [39] 0 0
Israel
State/province [39] 0 0
Zerifin
Country [40] 0 0
Italy
State/province [40] 0 0
Grosseto
Country [41] 0 0
Italy
State/province [41] 0 0
Milano
Country [42] 0 0
Italy
State/province [42] 0 0
Milan
Country [43] 0 0
Italy
State/province [43] 0 0
Napoli
Country [44] 0 0
Italy
State/province [44] 0 0
Roma
Country [45] 0 0
New Zealand
State/province [45] 0 0
Christchurch
Country [46] 0 0
Portugal
State/province [46] 0 0
Lisboa
Country [47] 0 0
Portugal
State/province [47] 0 0
Lisbon
Country [48] 0 0
Portugal
State/province [48] 0 0
Porto
Country [49] 0 0
Spain
State/province [49] 0 0
Gipuzkoa
Country [50] 0 0
Spain
State/province [50] 0 0
Barcelona
Country [51] 0 0
Spain
State/province [51] 0 0
Granollers
Country [52] 0 0
Spain
State/province [52] 0 0
Jaén
Country [53] 0 0
Spain
State/province [53] 0 0
Madrid
Country [54] 0 0
Spain
State/province [54] 0 0
Santa Cruz de Tenerife
Country [55] 0 0
Spain
State/province [55] 0 0
Sevilla
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Bradford
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Manchester
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Nektar Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is an open-label, randomized, active comparator, multicenter, international Phase 3
study of NKTR-102 versus TPC in patients with metastatic breast cancer who have stable brain
metastases and have been previously treated with an anthracycline, a taxane, and capecitabine
in either the adjuvant or metastatic setting (prior anthracycline may be omitted if medically
appropriate or contraindicated for the patient).
Trial website
https://clinicaltrials.gov/show/NCT02915744
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Nektar Recruitment
Address 0 0
Country 0 0
Phone 0 0
855-482-8676
Fax 0 0
Email 0 0
StudyInquiry@nektar.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02915744