Neoplasms

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Nervous System Diseases

Carcinoma

Neoplasm Metastasis

Breast Neoplasms

Brain Neoplasms

Breast Diseases

Skin Diseases

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Capecitabine

Vinorelbine

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Taxane

Etirinotecan pegol

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Enzyme Inhibitors

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.

NKTR-102

Eribulin

Ixabepilone

Nab-paclitaxel

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).

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.

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 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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The number of participants with adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3

Nektar Therapeutics

167 patients received at least one dose of study treatment and were included in the Safety population.

Treatment of Physician's Choice (TPC)

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.

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.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Grade - ECOG Performance Status

1. - Fully active, able to carry on all pre-disease performance without restriction
2. - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work

Eastern Cooperative Oncology Group (ECOG)

Of Child-Bearing Potential

Surgically Sterile

Post-Menopausal

Other

Missing

Reproductive Status

Performed

Positive

Negative

Borderline

Not Performed

Pregnancy Test at Screening

Height

Weight

Time since Initial Breast Cancer Diagnosis

Unknown

Stage 1: Primary Tumor is less than or equal to 20 mm in greatest dimension

Stage 2: Primary Tumor is greater than 20 mm but no less than or equal to 50 mm in greatest dimension

Stage 3: Primary Tumor is greater than 50 mm in greatest dimension

Stage 4: Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules)

Breast Cancer at Initial Diagnosis

Invasive Ductal Carcinoma

Invasive Lobular Carcinoma

Cancer Histology at Initial Diagnosis

ER Positive

ER Negative

Estrogen Receptor Status at Initial Diagnosis

PgR Positive

PgR Negative

Progesterone Receptor (PgR) Status at Initial Diagnosis

HER2 Positive

HER2 Negative

Human Epidermal Growth Factor Receptor (HER2) Status at Initial Diagnosis

Estrogen Receptor Status at Last Biopsy

Progesterone Receptor Status at Last Biopsy

HER2 Receptor Status at Last Biopsy

ER/PgR Positive

ER/PgR Negative

Estrogen Receptor/Progesterone Receptor Status at Last Biopsy

Time since Initial Brain Metastasis Diagnosis

Study Director

Overall Survival (OS) of Patients

Progression-Free Survival (Outside the Central Nervous System)

Progression-Free Survival in Brain Metastasis (PFS-BM)

Progression-Free Survival (Overall)

156 patients had measurable disease by RECIST v 1.1 at baseline and were included in the Response Evaluable population for this outcome.

Objective Response Rates (ORR) of the NKTR-102 Treatment and the Treatment of Physician's Choice (TPC)

# of Patients who achieved Complete Response

# of Patients who achieved Partial Response

# of Patients who have Stable Disease >= 120 days

# of Patients who achieved Clinical Benefit Rate (CBR)

Clinical Benefit Rate (CBR)

Duration of Response (DoR)

QLQ-C30 Score at Baseline

QLQ-C30 Score at End of Treatment, approximately 1 year

As the trial progressed, some patients discontinued study treatment as a result of progressive disease, non-PD AE, patient decision, or physician decision.

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.

EQ-5D-5L Score at Baseline

EQ-5D-5L Score at End of Treatment, approximately 1 year

Compare Health-Related Quality of Life (HRQoL) Using the the EuroQoL 5D (EQ-5D-5L™)

BFI Score at Baseline

BFI Score at End of Treatment, approximately 1 year

Compare Health-Related Quality of Life (HRQoL) Using the Brief Fatigue Inventory (BFI)

Magnitude of Clinical Benefit Assessed by ESMO-MCBS Derived From Overall Survival

167 patients received at least one dose of study treatment and were included in the Safety population for this outcome.

Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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	NCT02915744	Metastasis Breast Cancer	NKTR-102 Eribulin Ixabepilone Vinorelbine Gemcitabine Paclitaxel Docetaxel Nab-paclitaxel	18 Years -	Nektar Therapeutics
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	NCT02915744	Metastasis Breast Cancer	NKTR-102 Eribulin Ixabepilone Vinorelbine Gemcitabine Paclitaxel Docetaxel Nab-paclitaxel	18 Years -	Nektar Therapeutics

Spots Global Cancer Trial Database for breast cancer brain metastases (bcbm)