MetastasisPhase 3ATTAINNCT02915744
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
A Phase 3 study testing NKTR-102, Eribulin and Ixabepilone in people with Metastasis and Breast Cancer, run by Nektar Therapeutics at 56 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastasis, Breast Cancer
- What is being tested?
- NKTR-102, Eribulin and Ixabepilone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 178 participants
- Where
- 56 sitesin 10 countries
- Study dates
- Nov 2016to Jul 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
56 sites in 10 countries.
56 sites in 10 countries
United States19 sites
Investigator Site - Athens
Athens, Georgia, 30607
Investigator Site - Baltimore
Baltimore, Maryland, 21201
Investigator Site - Boston
Boston, Massachusetts, 02115
Investigator Site - Chapel Hill
Chapel Hill, North Carolina, 27599
Investigator Site - Columbus
Columbus, Ohio, 43210
Investigator Site - Fort Worth
Fort Worth, Texas, 76104
Investigator Site - Germantown
Germantown, Tennessee, 38138
Investigator Site - Houston
Houston, Texas, 77030
Investigator Site - Miami
Miami, Florida, 33136
Investigator Site - Minneapolis
Minneapolis, Minnesota, 55455
Investigator Site - New York
New York, New York, 10065
Investigator Site - Orange
Orange, California, 92868
Investigator Site - Plantation
Plantation, Florida, 33324
Investigator Site - Salt Lake City
Salt Lake City, Utah, 84106
Investigator Site - San Francisco
San Francisco, California, 94115
Investigator Site - Seattle
Seattle, Washington, 98109
Investigator Site - Saint Louis
St Louis, Missouri, 63110
Investigator Site - Tucson
Tucson, Arizona, 85724
Investigator Site - West Palm Beach
West Palm Beach, Florida, 33401
Belgium7 sites
Investigator Site - Brussels
Brussels, 1000
Investigator Site - Brussels
Brussels, 1180
Investigator Site - Brussels
Brussels, 1200
Investigator Site - Charleroi
Charleroi, 6000
Investigator Site - Edegem
Edegem, 2650
Investigator Site - Liege
Liège, 4000
Investigator Site - Woluwe- Saint-Lambert
Woluwe-Saint-Lambert, 1200
Australia6 sites
Investigatory Site - Albury
Albury, New South Wales, 2640
Investigator Site - Box Hill
Box Hill, 3128
Investigator Site - Darlinghurst
Darlinghurst, New South Wales, 2010
Investigator Site - Nedlands
Nedlands, 6009
Investigator Site - Subiaco
Subiaco, Western Australia, 6008
Investigator Site - Wollongong
Wollongong, New South Wales, 2500
France6 sites
Investigator Site - Le Mans
Le Mans, 72000
Investigator Site - Nimes
Nîmes, 30029
Investigator Site - Paris
Paris, 75248
Investigator Site - Rennes
Rennes, 35042
Investigator Site - Rouen
Rouen, 76038
Investigator Site - Strasbourg
Strasbourg, 67091
Spain5 sites
Investigator Site - Barcelona
Barcelona, 8023
Investigator Site - Barcelona
Barcelona, 8035
Investigator Site - Madrid
Madrid, 28040
Investigator Site - Santa Cruz de Tenerife
Santa Cruz de Tenerife, 38320
Investigator Site - Sevilla
Seville, 41013
Italy4 sites
Investigator Site - Milan
Milan, 20132
Investigator Site - Milano
Milan, 20141
Investigator Site - Napoli
Naples, 80131
Investigator Site - Roma
Roma, 144
Israel3 sites
Investigator Site - Beersheba
Beersheba, 84101
Investigator Site - Haifa
Haifa, 31096
Investigator Site - Tel Aviv
Tel Aviv, 64239
United Kingdom3 sites
Investigator Site - Bradford
Bradford, BD7 1DP
Investigator Site - Manchester
Manchester, M20 4BX
Investigator Site - Nottingham
Nottingham, NG5 1PB
Portugal2 sites
Investigator Site - Lisboa
Lisbon, 1649-035
Investigator Site - Porto
Porto, 4200-072
About this study
Official 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
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).
Read the detailed description
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).
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. 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.
This study will randomize approximately 220 patients using a 1:1 randomization ratio and stratification based on geographic region, tumor receptor status, and Eastern Cooperative Oncology Group (ECOG) status. At Screening, the Investigator must determine which TPC will be offered to the patient.
Data will be collected on subsequent anticancer therapies in both treatment groups from the time patients come off the study treatment until the time of primary data analysis for Overall Survival (OS).
An independent data monitoring committee (DMC) will assess interim safety and efficacy data and determine final number of death events needed to provide 80% conditional power based on the zone adaptive design.
- Conditions
- Metastasis, Breast Cancer
- Being tested
- NKTR-102, Eribulin, Ixabepilone, Vinorelbine, Gemcitabine
- Keywords
- Breast Cancer Brain Metastases (BCBM), Carcinoma
- Medical subject headings
- Neoplasm Metastasis, Breast Neoplasms, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NKTR-102Drug
EribulinDrug
IxabepiloneDrug
VinorelbineDrug
GemcitabineDrug
PaclitaxelDrug
DocetaxelDrug
Nab-paclitaxelDrug
| Study group | Role | What they receive |
|---|---|---|
| NKTR-102 | Experimental | 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. Receives: Drug: NKTR-102 |
| Treatment of Physician's Choice (TPC) | Active comparator | 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. Receives: Drug: Eribulin; Drug: Ixabepilone; Drug: Vinorelbine; Drug: Gemcitabine; Drug: Paclitaxel; Drug: Docetaxel; Drug: Nab-paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Within 3 years from study start
Secondary outcomes (11)
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. The assessment of PFS outside the CNS will utilize RECIST criteria v1.1.
Measured: Through study completion, an expected average of 1 year
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. Progressive Disease (PD) is defined as at least a 20% increase in the sum of longest diameters of CNS target lesions, taking as reference the smallest sum on study. This included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, at least 1 lesion had to increase by an absolute value of 5 mm or more to be considered progression.
Measured: Through study completion, an expected average of 1 year
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). Progressive Disease (PD) is defined as at least a 20% increase in the sum of longest diameters of CNS target lesions, taking as reference the smallest sum on study. This included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, at least 1 lesion had to increase by an absolute value of 5 mm or more to be considered progression.
Measured: Through study completion, an expected average of 1 year
Objective Response Rates (ORR) of the NKTR-102 Treatment and the Treatment of Physician's Choice (TPC)
RECIST criteria for lesions outside the Central Nervous System (CNS); RANO-BM criteria for CNS lesions) based upon the best response as assessed by the central imaging facility. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR. Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: Through study completion, an expected average of 1 year
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). CR is defined as disappearance of all target lesions for at least 4 weeks with no new lesions, not use of corticosteroids, and patient was stable or improved clinically. PR is defined as at least a 30% decrease in the sum of longest diameters sustained for at least 4 weeks, no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: For at least 4 months, with an expected average of 1 year
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. CR is defined as disappearance of all target lesions for at least 4 weeks with no new lesions, not use of corticosteroids, and patient was stable or improved clinically. PR is defined as at least a 30% decrease in the sum of longest diameters sustained for at least 4 weeks, no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: Through study completion, an expected average of 1 year
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.
The EORTC QLQ-BN20 Scale has a series of 20 questions each of which involve reporting a scale from 1-4. It is an increasing scale where a score of one indicates "not at all" while a score of four indicates "very much". The minimum score is 20 and the maximum score is 80. The higher the score the worse the outcome.
Measured: Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 for NKTR-102 or 28 days for TPC] and end of Cycle 44.
Compare Health-Related Quality of Life (HRQoL) Using the the EuroQoL 5D (EQ-5D-5L™)
The EQ-5D-5L scale is used to measure health by having a patient answer a series of questions. There are a series of 5 questions each of which is scaled from a score of 4-20 in increasing increments of 4. The scale is numbered from 0 to 100 where 100 means the beast health you can imagine and 0 means the worst health.
Measured: Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 for NKTR-102 or 28 days for TPC] and end of Cycle 44
Compare Health-Related Quality of Life (HRQoL) Using the Brief Fatigue Inventory (BFI)
The Brief Fatigue Inventory scale utilizes a series of 4 questions. The first three are scored with a scale from 1-10. The fourth question has 6 six sub components each of which are scored with a scale of 1-10. For every scale, a score of 0 indicates no fatigue/interference where a score of 10 indicates as bad as you can imagine. A patient's score can range from 0 to 100 where 0 indicates the best outcome and 100 indicates the worst.
Measured: Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 for NKTR-102 or 28 days for TPC] and end of Cycle 44
Magnitude of Clinical Benefit Assessed by ESMO-MCBS Derived From Overall Survival
The magnitude of clinical benefit of NKTR-102 is assessed by the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) (v1.0). The scale is graded 5, 4, 3, 2, 1, where grades 5 and 4 represent a high level of proven clinical benefit, and grade 1 represents no clinical benefit. To determine the magnitude of clinical benefit when the median OS with the standard of treatment is ≤ 1 year, the score is derived from the Hazard Ratio (HR) of Overall Survival, overall survival gain, and QoL improvement between two treatment arms. Values reported in the data table are Overall Survival values.
Measured: Through study completion, within 3 years from study start
Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3
The number of participants with adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3
Measured: Through study completion, an expected average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2016 (estimated)
- Study startNov 2016
- Primary completionJul 2020
- Study completionJul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MetastasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 178 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nektar Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02915744
- Sponsor's protocol ID
- 15-102-14
- Acronym
- ATTAIN
- Status last verified
- Apr 2023
- First submitted
- 22 Sep 2016
- Last updated
- 14 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Dieras V, Muller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortes J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. doi: 10.1001/jamaoncol.2022.0514.
PubMed 35552364Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Dieras V, Muller V, Tagliaferri M, Hannah AL, Cortes J. ATTAIN: Phase III study of etirinotecan pegol versus treatment of physician's choice in patients with metastatic breast cancer and brain metastases. Future Oncol. 2019 Jul;15(19):2211-2225. doi: 10.2217/fon-2019-0180. Epub 2019 May 10.
PubMed 31074641
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02915744
- Acronym / sponsor ID
- ATTAIN / 15-102-14
- Conditions
- Metastasis, Breast Cancer
- Keywords
- Breast Cancer Brain Metastases (BCBM), Carcinoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 178 participants (actual)
- Lead sponsor
- Nektar TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Nov 2016
- Primary completion
- Jul 2020 (actual)
- Study completion
- Jul 2020 (actual)
- First posted
- 27 Sep 2016 (estimated)
- Results
- Posted 27 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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).
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. 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.
This study will randomize approximately 220 patients using a 1:1 randomization ratio and stratification based on geographic region, tumor receptor status, and Eastern Cooperative Oncology Group (ECOG) status. At Screening, the Investigator must determine which TPC will be offered to the patient.
Data will be collected on subsequent anticancer therapies in both treatment groups from the time patients come off the study treatment until the time of primary data analysis for Overall Survival (OS).
An independent data monitoring committee (DMC) will assess interim safety and efficacy data and determine final number of death events needed to provide 80% conditional power based on the zone adaptive design.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NKTR-102 | Experimental | Drug: NKTR-102In 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. |
| Treatment of Physician's Choice (TPC) | Active comparator | Drug: Eribulin, Drug: Ixabepilone, Drug: Vinorelbine, Drug: Gemcitabine, Drug: Paclitaxel, Drug: Docetaxel, Drug: Nab-paclitaxelIn 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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).
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NKTR-102 | Drug | NKTR-102 |
| Eribulin | Drug | Treatment of Physician's Choice (TPC) |
| Ixabepilone | Drug | Treatment of Physician's Choice (TPC) |
| Vinorelbine | Drug | Treatment of Physician's Choice (TPC) |
| Gemcitabine | Drug | Treatment of Physician's Choice (TPC) |
| Paclitaxel | Drug | Treatment of Physician's Choice (TPC) |
| Docetaxel | Drug | Treatment of Physician's Choice (TPC) |
| Nab-paclitaxel | Drug | Treatment of Physician's Choice (TPC) |
Primary outcome
Overall Survival (OS) of Patients
Time frame: Within 3 years from study start
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.
11 secondary outcomes
Progression-Free Survival (Outside the Central Nervous System)
Time frame: Through study completion, an expected average of 1 year
Progression-Free Survival in Brain Metastasis (PFS-BM)
Time frame: Through study completion, an expected average of 1 year
Progression-Free Survival (Overall)
Time frame: Through study completion, an expected average of 1 year
Objective Response Rates (ORR) of the NKTR-102 Treatment and the Treatment of Physician's Choice (TPC)
Time frame: Through study completion, an expected average of 1 year
Clinical Benefit Rate (CBR)
Time frame: For at least 4 months, with an expected average of 1 year
Duration of Response (DoR)
Time frame: Through study completion, an expected average of 1 year
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.
Time frame: Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 for NKTR-102 or 28 days for TPC] and end of Cycle 44.
Compare Health-Related Quality of Life (HRQoL) Using the the EuroQoL 5D (EQ-5D-5L™)
Time frame: Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 for NKTR-102 or 28 days for TPC] and end of Cycle 44
Compare Health-Related Quality of Life (HRQoL) Using the Brief Fatigue Inventory (BFI)
Time frame: Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 for NKTR-102 or 28 days for TPC] and end of Cycle 44
Magnitude of Clinical Benefit Assessed by ESMO-MCBS Derived From Overall Survival
Time frame: Through study completion, within 3 years from study start
Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3
Time frame: Through study completion, an expected average of 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35552364Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Dieras V, Muller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortes J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. doi: 10.1001/jamaoncol.2022.0514.
- Derived from this study: PubMed 31074641Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Dieras V, Muller V, Tagliaferri M, Hannah AL, Cortes J. ATTAIN: Phase III study of etirinotecan pegol versus treatment of physician's choice in patients with metastatic breast cancer and brain metastases. Future Oncol. 2019 Jul;15(19):2211-2225. doi: 10.2217/fon-2019-0180. Epub 2019 May 10.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
56 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NKTR-102, Eribulin and Ixabepilone in people with Metastasis and Breast Cancer, run by Nektar Therapeutics at 56 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in United States, Belgium, Australia, France, Spain and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) of Patients (time frame: Within 3 years from study start). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02915744, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2023.