ATTAIN: 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
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Drug: NKTR-102
|
| 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. |
Drug: Eribulin
Drug: Ixabepilone
Drug: Vinorelbine
Drug: Gemcitabine
Drug: Paclitaxel
Drug: Docetaxel
Drug: Nab-paclitaxel
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) of Patients [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.
Secondary Outcome Measures
- Progression-Free Survival (Outside the Central Nervous System) [Through study completion, an expected average of 1 year]
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) [Through study completion, an expected average of 1 year]
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.
- Progression-Free Survival (Overall) [Through study completion, an expected average of 1 year]
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).
- Objective Response Rates (ORR) of the NKTR-102 Treatment and the Treatment of Physician's Choice (TPC) [Through study completion, an expected average of 1 year]
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 (CBR) [For at least 4 months, with an expected average of 1 year]
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.
- Duration of Response (DoR) [Through study completion, an expected average of 1 year]
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.
- Whole Brain Radiotherapy (WBRT) [Through study completion, an expected average of 1 year]
To compare the incidence of WBRT after date of randomization by treatment group.
- 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. [Through study completion, an expected average of 1 year]
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.
- Compare Health-Related Quality of Life (HRQoL) Using the the EuroQoL 5D (EQ-5D-5L™) [Through study completion, an expected average of 1 year]
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.
- Compare Health-Related Quality of Life (HRQoL) Using the Brief Fatigue Inventory (BFI) [Through study completion, an expected average of 1 year]
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.
- Magnitude of Clinical Benefit [Through study completion, an expected average of 1 year]
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).
- Maximum Observed Serum Concentration (Cmax) of NKTR-102 [Through study completion, an expected average of 1 year]
The maximum concentration of NKTR-102 reached in the bloodstream post administration.
- Time of Maximum Observed Serum Concentration (Tmax) of NKTR-102 [Through study completion, an expected average of 1 year]
The time it takes to reach the maximum concentration of NKTR-102 in the bloodstream.
- Area Under Serum Concentration Time Curve [Through study completion, an expected average of 1 year]
The area under the curve of a concentration vs. time graph in the dosing interval (AUCtau) of NKTR-102
- Half-life of (t1/2) of NKTR-102 [Through study completion, an expected average of 1 year]
The amount of time necessary to degrade 50% of the NKTR-102 administered.
- Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3 [Through study completion, an expected average of 1 year]
The number of participants with adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3
Eligibility Criteria
Criteria
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.
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigator Site - Tucson | Tucson | Arizona | United States | 85724 |
| 2 | Investigator Site - Orange | Orange | California | United States | 92868 |
| 3 | Investigator Site - San Francisco | San Francisco | California | United States | 94115 |
| 4 | Investigator Site - Miami | Miami | Florida | United States | 33136 |
| 5 | Investigator Site - Plantation | Plantation | Florida | United States | 33324 |
| 6 | Investigator Site - West Palm Beach | West Palm Beach | Florida | United States | 33401 |
| 7 | Investigator Site - Athens | Athens | Georgia | United States | 30607 |
| 8 | Investigator Site - Baltimore | Baltimore | Maryland | United States | 21201 |
| 9 | Investigator Site - Boston | Boston | Massachusetts | United States | 02115 |
| 10 | Investigator Site - Minneapolis | Minneapolis | Minnesota | United States | 55455 |
| 11 | Investigator Site - Saint Louis | Saint Louis | Missouri | United States | 63110 |
| 12 | Investigator Site - New York | New York | New York | United States | 10065 |
| 13 | Investigator Site - Chapel Hill | Chapel Hill | North Carolina | United States | 27599 |
| 14 | Investigator Site - Columbus | Columbus | Ohio | United States | 43210 |
| 15 | Investigator Site - Germantown | Germantown | Tennessee | United States | 38138 |
| 16 | Investigator Site - Fort Worth | Fort Worth | Texas | United States | 76104 |
| 17 | Investigator Site - Houston | Houston | Texas | United States | 77030 |
| 18 | Investigator Site - Salt Lake City | Salt Lake City | Utah | United States | 84106 |
| 19 | Investigator Site - Seattle | Seattle | Washington | United States | 98109 |
| 20 | Investigatory Site - Albury | Albury | New South Wales | Australia | 2640 |
| 21 | Investigator Site - Darlinghurst | Darlinghurst | New South Wales | Australia | 2010 |
| 22 | Investigator Site - Wollongong | Wollongong | New South Wales | Australia | 2500 |
| 23 | Investigator Site - Subiaco | Subiaco | Western Australia | Australia | 6008 |
| 24 | Investigator Site - Box Hill | Box Hill | Australia | 3128 | |
| 25 | Investigator Site - Nedlands | Nedlands | Australia | 6009 | |
| 26 | Investigator Site - Brussels | Brussels | Belgium | 1000 | |
| 27 | Investigator Site - Brussels | Brussels | Belgium | 1180 | |
| 28 | Investigator Site - Brussels | Brussels | Belgium | 1200 | |
| 29 | Investigator Site - Charleroi | Charleroi | Belgium | 6000 | |
| 30 | Investigator Site - Edegem | Edegem | Belgium | 2650 | |
| 31 | Investigator Site - Liege | Liège | Belgium | 4000 | |
| 32 | Investigator Site - Woluwe- Saint-Lambert | Woluwe-Saint-Lambert | Belgium | 1200 | |
| 33 | Investigator Site - Montreal | Montréal | Quebec | Canada | H4A 3J1 |
| 34 | Investigator Site - Le Mans | Le Mans | France | 72000 | |
| 35 | Investigator Site - Nimes | Nîmes | France | 30029 | |
| 36 | Investigator Site - Paris | Paris | France | 75248 | |
| 37 | Investigator Site - Rennes | Rennes | France | 35042 | |
| 38 | Investigator Site - Rouen | Rouen | France | 76038 | |
| 39 | Investigator Site - Strasbourg | Strasbourg | France | 67091 | |
| 40 | Investigator Site - Beersheba | Beersheba | Israel | 84101 | |
| 41 | Investigator Site - Haifa | Haifa | Israel | 31096 | |
| 42 | Investigator Site - Tel Aviv | Tel Aviv | Israel | 64239 | |
| 43 | Investigator Site - Milano | Milano | Italy | 20141 | |
| 44 | Investigator Site - Milan | Milan | Italy | 20132 | |
| 45 | Investigator Site - Napoli | Napoli | Italy | 80131 | |
| 46 | Investigator Site - Roma | Roma | Italy | 144 | |
| 47 | Investigator Site - Lisboa | Lisboa | Portugal | 1649-035 | |
| 48 | Investigator Site - Porto | Porto | Portugal | 4200-072 | |
| 49 | Investigator Site - Barcelona | Barcelona | Spain | 8023 | |
| 50 | Investigator Site - Barcelona | Barcelona | Spain | 8035 | |
| 51 | Investigator Site - Madrid | Madrid | Spain | 28040 | |
| 52 | Investigator Site - Santa Cruz de Tenerife | Santa Cruz de Tenerife | Spain | 38320 | |
| 53 | Investigator Site - Sevilla | Sevilla | Spain | 41013 | |
| 54 | Investigator Site - Bradford | Bradford | United Kingdom | BD7 1DP | |
| 55 | Investigator Site - Manchester | Manchester | United Kingdom | M20 4BX | |
| 56 | Investigator Site - Nottingham | Nottingham | United Kingdom | NG5 1PB |
Sponsors and Collaborators
- Nektar Therapeutics
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- 15-102-14
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | ||
| STARTED | 92 | 86 |
| COMPLETED | 13 | 9 |
| NOT COMPLETED | 79 | 77 |
Baseline Characteristics
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) | Total |
|---|---|---|---|
| Arm/Group Description | 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 of all reporting groups |
| Overall Participants | 92 | 86 | 178 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
54.7
(10.13)
|
51.9
(10.50)
|
53.3
(10.37)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
92
100%
|
86
100%
|
178
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
2
2.2%
|
6
7%
|
8
4.5%
|
| Not Hispanic or Latino |
69
75%
|
60
69.8%
|
129
72.5%
|
| Unknown or Not Reported |
21
22.8%
|
20
23.3%
|
41
23%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
3
3.3%
|
6
7%
|
9
5.1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
3
3.3%
|
5
5.8%
|
8
4.5%
|
| White |
66
71.7%
|
57
66.3%
|
123
69.1%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
20
21.7%
|
18
20.9%
|
38
21.3%
|
| Eastern Cooperative Oncology Group (ECOG) (Count of Participants) | |||
| 0 |
25
27.2%
|
25
29.1%
|
50
28.1%
|
| 1 |
67
72.8%
|
61
70.9%
|
128
71.9%
|
| Reproductive Status (Count of Participants) | |||
| Of Child-Bearing Potential |
16
17.4%
|
13
15.1%
|
29
16.3%
|
| Surgically Sterile |
11
12%
|
14
16.3%
|
25
14%
|
| Post-Menopausal |
65
70.7%
|
55
64%
|
120
67.4%
|
| Other |
0
0%
|
4
4.7%
|
4
2.2%
|
| Missing |
0
0%
|
0
0%
|
0
0%
|
| Pregnancy Test at Screening (Count of Participants) | |||
| Performed |
29
31.5%
|
26
30.2%
|
55
30.9%
|
| Positive |
1
1.1%
|
1
1.2%
|
2
1.1%
|
| Negative |
22
23.9%
|
24
27.9%
|
46
25.8%
|
| Borderline |
6
6.5%
|
1
1.2%
|
7
3.9%
|
| Not Performed |
63
68.5%
|
60
69.8%
|
123
69.1%
|
| Height (centimeters) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [centimeters] |
162.7
(6.67)
|
162.1
(7.73)
|
162.4
(7.19)
|
| Weight (kilograms) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kilograms] |
67.16
(17.468)
|
65.97
(15.561)
|
66.59
(16.539)
|
| Time since Initial Breast Cancer Diagnosis (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
8.094
(5.1700)
|
6.950
(5.0941)
|
7.541
(5.151)
|
| Breast Cancer at Initial Diagnosis (Count of Participants) | |||
| I |
5
5.4%
|
10
11.6%
|
15
8.4%
|
| II |
41
44.6%
|
29
33.7%
|
70
39.3%
|
| III |
22
23.9%
|
17
19.8%
|
39
21.9%
|
| IV |
10
10.9%
|
16
18.6%
|
26
14.6%
|
| Unknown |
14
15.2%
|
14
16.3%
|
28
15.7%
|
| Cancer Histology at Initial Diagnosis (Count of Participants) | |||
| Invasive Ductal Carcinoma |
80
87%
|
77
89.5%
|
157
88.2%
|
| Invasive Lobular Carcinoma |
6
6.5%
|
1
1.2%
|
7
3.9%
|
| Other |
6
6.5%
|
8
9.3%
|
14
7.9%
|
| Estrogen Receptor Status at Initial Diagnosis (Count of Participants) | |||
| ER Positive |
52
56.5%
|
49
57%
|
101
56.7%
|
| ER Negative |
40
43.5%
|
34
39.5%
|
74
41.6%
|
| Unknown |
0
0%
|
3
3.5%
|
3
1.7%
|
| Progesterone Receptor (PgR) Status at Initial Diagnosis (Count of Participants) | |||
| PgR Positive |
40
43.5%
|
42
48.8%
|
82
46.1%
|
| PgR Negative |
50
54.3%
|
41
47.7%
|
91
51.1%
|
| Unknown |
2
2.2%
|
3
3.5%
|
5
2.8%
|
| Human Epidermal Growth Factor Receptor (HER2) Status at Initial Diagnosis (Count of Participants) | |||
| HER2 Positive |
15
16.3%
|
14
16.3%
|
29
16.3%
|
| HER2 Negative |
76
82.6%
|
66
76.7%
|
142
79.8%
|
| Unknown |
1
1.1%
|
6
7%
|
7
3.9%
|
| Estrogen Receptor Status at Last Biopsy (Count of Participants) | |||
| ER Positive |
47
51.1%
|
48
55.8%
|
95
53.4%
|
| ER Negative |
38
41.3%
|
36
41.9%
|
74
41.6%
|
| Unknown |
7
7.6%
|
2
2.3%
|
9
5.1%
|
| Progesterone Receptor Status at Last Biopsy (Count of Participants) | |||
| PgR Positive |
32
34.8%
|
31
36%
|
63
35.4%
|
| PgR Negative |
51
55.4%
|
52
60.5%
|
103
57.9%
|
| Unknown |
9
9.8%
|
3
3.5%
|
12
6.7%
|
| HER2 Receptor Status at Last Biopsy (Count of Participants) | |||
| HER2 Positive |
12
13%
|
13
15.1%
|
25
14%
|
| HER2 Negative |
74
80.4%
|
69
80.2%
|
143
80.3%
|
| Unknown |
6
6.5%
|
4
4.7%
|
10
5.6%
|
| Estrogen Receptor/Progesterone Receptor Status at Last Biopsy (Count of Participants) | |||
| ER/PgR Positive |
49
53.3%
|
49
57%
|
98
55.1%
|
| ER/PgR Negative |
36
39.1%
|
35
40.7%
|
71
39.9%
|
| Unknown |
7
7.6%
|
2
2.3%
|
9
5.1%
|
| Time since Initial Brain Metastasis Diagnosis (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
1.137
(1.1061)
|
1.194
(1.1748)
|
1.165
(1.1369)
|
Outcome Measures
| Title | Overall Survival (OS) of Patients |
|---|---|
| Description | 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. |
| Time Frame | Within 3 years from study start |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 92 | 86 |
| Median (95% Confidence Interval) [months] |
7.8
|
7.5
|
| Title | Progression-Free Survival (Outside the Central Nervous System) |
|---|---|
| Description | 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. |
| Time Frame | Through study completion, an expected average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 92 | 86 |
| Median (95% Confidence Interval) [months] |
2.8
|
1.9
|
| Title | Progression-Free Survival in Brain Metastasis (PFS-BM) |
|---|---|
| Description | 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. |
| Time Frame | Through study completion, an expected average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 92 | 86 |
| Median (95% Confidence Interval) [months] |
3.9
|
3.3
|
| Title | Progression-Free Survival (Overall) |
|---|---|
| Description | 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). |
| Time Frame | Through study completion, an expected average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 92 | 86 |
| Median (95% Confidence Interval) [months] |
2.1
|
1.9
|
| Title | Objective Response Rates (ORR) of the NKTR-102 Treatment and the Treatment of Physician's Choice (TPC) |
|---|---|
| Description | 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. |
| Time Frame | Through study completion, an expected average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| 156 patients had measurable disease by RECIST v 1.1 at baseline and were included in the Response Evaluable population for this outcome. |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 83 | 73 |
| Objective Response Rate (CR+PR) |
4
4.3%
|
2
2.3%
|
| Stable Disease |
16
17.4%
|
5
5.8%
|
| Progressive Disease |
38
41.3%
|
32
37.2%
|
| Not Evaluable |
18
19.6%
|
30
34.9%
|
| Missing |
7
7.6%
|
4
4.7%
|
| Title | Clinical Benefit Rate (CBR) |
|---|---|
| Description | 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. |
| Time Frame | For at least 4 months, with an expected average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 92 | 86 |
| # of Patients who achieved Complete Response |
0
0%
|
0
0%
|
| # of Patients who achieved Partial Response |
6
6.5%
|
6
7%
|
| # of Patients who have Stable Disease >= 120 days |
17
18.5%
|
5
5.8%
|
| # of Patients who achieved Clinical Benefit Rate (CBR) |
23
25%
|
11
12.8%
|
| Title | Duration of Response (DoR) |
|---|---|
| Description | 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. |
| Time Frame | Through study completion, an expected average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 83 | 73 |
| Median (Inter-Quartile Range) [months] |
7.4
|
3.5
|
| Title | Whole Brain Radiotherapy (WBRT) |
|---|---|
| Description | To compare the incidence of WBRT after date of randomization by treatment group. |
| Time Frame | Through study completion, an expected average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| As a result of this study being terminated early, data for this outcome was not collected. |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 | 0 |
| Title | 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. |
|---|---|
| Description | 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. |
| Time Frame | Through study completion, an expected average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| As the trial progressed, some patients discontinued study treatment as a result of progressive disease, non-PD AE, patient decision, or physician decision. |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 79 | 63 |
| QLQ-C30 Score at Baseline |
57.59
(21.607)
|
52.25
(24.236)
|
| QLQ-C30 Score at End of Treatment, approximately 1 year |
46.97
(24.582)
|
52.38
(24.801)
|
| Title | Compare Health-Related Quality of Life (HRQoL) Using the the EuroQoL 5D (EQ-5D-5L™) |
|---|---|
| Description | 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. |
| Time Frame | Through study completion, an expected average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| As the trial progressed, some patients discontinued study treatment as a result of progressive disease, non-PD AE, patient decision, or physician decision. |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 80 | 63 |
| EQ-5D-5L Score at Baseline |
61.41
(19.739)
|
60.33
(23.004)
|
| EQ-5D-5L Score at End of Treatment, approximately 1 year |
56.53
(23.467)
|
61.60
(20.858)
|
| Title | Compare Health-Related Quality of Life (HRQoL) Using the Brief Fatigue Inventory (BFI) |
|---|---|
| Description | 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. |
| Time Frame | Through study completion, an expected average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| As the trial progressed, some patients discontinued study treatment as a result of progressive disease, non-PD AE, patient decision, or physician decision. |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 79 | 62 |
| BFI Score at Baseline |
4.18
(2.264)
|
4.04
(2.401)
|
| BFI Score at End of Treatment, approximately 1 year |
4.83
(2.476)
|
4.74
(2.373)
|
| Title | Magnitude of Clinical Benefit |
|---|---|
| Description | 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). |
| Time Frame | Through study completion, an expected average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| As a result of this study being terminated early, data was not collected for this outcome. |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 | 0 |
| Title | Maximum Observed Serum Concentration (Cmax) of NKTR-102 |
|---|---|
| Description | The maximum concentration of NKTR-102 reached in the bloodstream post administration. |
| Time Frame | Through study completion, an expected average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| As a result of this study being terminated early, data was not collected for this outcome. |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 | 0 |
| Title | Time of Maximum Observed Serum Concentration (Tmax) of NKTR-102 |
|---|---|
| Description | The time it takes to reach the maximum concentration of NKTR-102 in the bloodstream. |
| Time Frame | Through study completion, an expected average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| As a result of this study being terminated early, data was not collected for this outcome. |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 | 0 |
| Title | Area Under Serum Concentration Time Curve |
|---|---|
| Description | The area under the curve of a concentration vs. time graph in the dosing interval (AUCtau) of NKTR-102 |
| Time Frame | Through study completion, an expected average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| As a result of this study being terminated early, data was not collected for this outcome. |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 | 0 |
| Title | Half-life of (t1/2) of NKTR-102 |
|---|---|
| Description | The amount of time necessary to degrade 50% of the NKTR-102 administered. |
| Time Frame | Through study completion, an expected average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| As a result of this study being terminated early, data was not collected for this outcome. |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 | 0 |
| Title | Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3 |
|---|---|
| Description | The 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 167 patients received at least one dose of study treatment and were included in the Safety population for this outcome. |
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) |
|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 90 | 77 |
| Count of Participants [Participants] |
90
97.8%
|
76
88.4%
|
Adverse Events
| Time Frame | The adverse event data was collected over the entire course of the study or approximately 2 years and 8 months. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | 167 patients received at least one dose of study treatment and were included in the Safety population. | |||
| Arm/Group Title | NKTR-102 | Treatment of Physician's Choice (TPC) | ||
| Arm/Group Description | 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. | ||
All Cause Mortality |
||||
| NKTR-102 | Treatment of Physician's Choice (TPC) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/90 (2.2%) | 0/77 (0%) | ||
Serious Adverse Events |
||||
| NKTR-102 | Treatment of Physician's Choice (TPC) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 33/90 (36.7%) | 24/77 (31.2%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile Neutropenia Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Cardiac disorders | ||||
| Atrial Fibrillation Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Cardiac Tamponade Grade 4 | 0/90 (0%) | 1/77 (1.3%) | ||
| Eye disorders | ||||
| Blindness Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Gastrointestinal disorders | ||||
| Colitis Grade 2 | 1/90 (1.1%) | 0/77 (0%) | ||
| Esophagitis Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Vomiting Grade 2 | 3/90 (3.3%) | 1/77 (1.3%) | ||
| Diarrhea Grade 3 | 5/90 (5.6%) | 0/77 (0%) | ||
| Intestinal Obstruction Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Nausea Grade 2 | 0/90 (0%) | 1/77 (1.3%) | ||
| Colitis Grade 3 | 3/90 (3.3%) | 0/77 (0%) | ||
| Vomiting Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Neutropenic Colitis Grade 4 | 1/90 (1.1%) | 0/77 (0%) | ||
| General disorders | ||||
| Abdominal Pain Grade 2 | 0/90 (0%) | 1/77 (1.3%) | ||
| Dysphagia Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Abdominal Pain Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Generalized Physical Health Deterioration Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Generalized Physical Health Deterioration Grade 5 | 1/90 (1.1%) | 0/77 (0%) | ||
| Asthenia Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Fatigue Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Hepatobiliary disorders | ||||
| Hyperbilirubinemia | 0/90 (0%) | 2/77 (2.6%) | ||
| Bile Duct Stone Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Cholecystitis Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Hepatic Function Abnormal Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Hepatic Failure Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Hyperbilirubinemia Grade 3 | 0/90 (0%) | 2/77 (2.6%) | ||
| Immune system disorders | ||||
| Leukopenia Grade 4 | 1/90 (1.1%) | 0/77 (0%) | ||
| Neutropenia Grade 4 | 3/90 (3.3%) | 0/77 (0%) | ||
| Normochromic normocytic Anemia Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Infections and infestations | ||||
| Pneumonia Grade 3 | 1/90 (1.1%) | 1/77 (1.3%) | ||
| Device Related Infection Grade 4 | 1/90 (1.1%) | 0/77 (0%) | ||
| Neutropenic Sepsis Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Viral Gastroenteritis Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Urinary Tract Infection Grade 3 | 1/90 (1.1%) | 1/77 (1.3%) | ||
| Esophageal Candidiasis Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Bacteremia Grade 4 | 0/90 (0%) | 1/77 (1.3%) | ||
| Pneumonia Grade 5 | 1/90 (1.1%) | 0/77 (0%) | ||
| Cellulitis Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Device Related Sepsis Grade 4 | 1/90 (1.1%) | 0/77 (0%) | ||
| Lung Infection Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Escherichia Sepsis Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Pyoderma Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Influenza Grade 4 | 1/90 (1.1%) | 0/77 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Investigations | ||||
| Neutrophil Count Decrease Grade 4 | 0/90 (0%) | 1/77 (1.3%) | ||
| Metabolism and nutrition disorders | ||||
| Hyponatremia Grade 3 | 1/90 (1.1%) | 1/77 (1.3%) | ||
| Dehydration Grade 3 | 2/90 (2.2%) | 0/77 (0%) | ||
| Failure to Thrive Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Hypercalcemia Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Hip Fracture Grade 3 | 1/90 (1.1%) | 2/77 (2.6%) | ||
| Fatigue Grade 2 | 0/90 (0%) | 1/77 (1.3%) | ||
| Contusion Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Groin Pain Grade 2 | 1/90 (1.1%) | 0/77 (0%) | ||
| Muscle Spasm Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Pathological Fracture Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Back Pain Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Paresthesia Grade 2 | 1/90 (1.1%) | 0/77 (0%) | ||
| Nervous system disorders | ||||
| Brain Edema Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Malaise Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Dizziness Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Epilepsy Grade 2 | 1/90 (1.1%) | 0/77 (0%) | ||
| Fine motor skill dysfunction Grade 2 | 1/90 (1.1%) | 0/77 (0%) | ||
| Hypoesthesia Grade 2 | 1/90 (1.1%) | 0/77 (0%) | ||
| Seizure Grade 2 | 1/90 (1.1%) | 1/77 (1.3%) | ||
| Syncope Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Status Epilepticus Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Psychiatric disorders | ||||
| Confusional State Grade 2 | 1/90 (1.1%) | 0/77 (0%) | ||
| Confusional State Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Mental Status Changes Grade 3 | 1/90 (1.1%) | 0/77 (0%) | ||
| Hallucination Grade 4 | 0/90 (0%) | 1/77 (1.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pleural Effusion Grade 3 | 1/90 (1.1%) | 1/77 (1.3%) | ||
| Pneumothorax Grade 2 | 1/90 (1.1%) | 0/77 (0%) | ||
| Dyspnea Grade 2 | 0/90 (0%) | 1/77 (1.3%) | ||
| Dyspnea Grade 3 | 0/90 (0%) | 1/77 (1.3%) | ||
| Vascular disorders | ||||
| Deep Vein Thrombosis Grade 4 | 0/90 (0%) | 1/77 (1.3%) | ||
Other (Not Including Serious) Adverse Events |
||||
| NKTR-102 | Treatment of Physician's Choice (TPC) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 90/90 (100%) | 76/77 (98.7%) | ||
| Blood and lymphatic system disorders | ||||
| Neutropenia | 17/90 (18.9%) | 18/77 (23.4%) | ||
| Anemia | 11/90 (12.2%) | 17/77 (22.1%) | ||
| Thrombocytopenia | 5/90 (5.6%) | 5/77 (6.5%) | ||
| Leukopenia | 5/90 (5.6%) | 3/77 (3.9%) | ||
| Eye disorders | ||||
| Vision Blurred | 10/90 (11.1%) | 2/77 (2.6%) | ||
| Gastrointestinal disorders | ||||
| Diarrhea | 66/90 (73.3%) | 15/77 (19.5%) | ||
| Constipation | 24/90 (26.7%) | 20/77 (26%) | ||
| Stomatitis | 4/90 (4.4%) | 5/77 (6.5%) | ||
| Abdominal Distension | 7/90 (7.8%) | 1/77 (1.3%) | ||
| Flatulence | 5/90 (5.6%) | 1/77 (1.3%) | ||
| Dyspepsia | 5/90 (5.6%) | 0/77 (0%) | ||
| Pyrexia | 6/90 (6.7%) | 7/77 (9.1%) | ||
| Oedema Peripheral | 6/90 (6.7%) | 5/77 (6.5%) | ||
| General disorders | ||||
| Nausea | 54/90 (60%) | 31/77 (40.3%) | ||
| Vomiting | 34/90 (37.8%) | 17/77 (22.1%) | ||
| Fatigue | 36/90 (40%) | 26/77 (33.8%) | ||
| Asthenia | 28/90 (31.1%) | 16/77 (20.8%) | ||
| Pain | 5/90 (5.6%) | 4/77 (5.2%) | ||
| Infections and infestations | ||||
| Stomatitis | 4/90 (4.4%) | 5/77 (6.5%) | ||
| Urinary Tract Infection | 8/90 (8.9%) | 3/77 (3.9%) | ||
| Investigations | ||||
| Neutrophil Count Decreased | 6/90 (6.7%) | 10/77 (13%) | ||
| Aspartate Aminotransferase Increased | 5/90 (5.6%) | 9/77 (11.7%) | ||
| Weight Decreased | 13/90 (14.4%) | 1/77 (1.3%) | ||
| Alanine Aminotransferase Increased | 2/90 (2.2%) | 9/77 (11.7%) | ||
| Platelet Count Decresed | 3/90 (3.3%) | 4/77 (5.2%) | ||
| White Blood Cell Count Decreased | 2/90 (2.2%) | 4/77 (5.2%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased Appetite | 33/90 (36.7%) | 14/77 (18.2%) | ||
| Hypokalemia | 16/90 (17.8%) | 4/77 (5.2%) | ||
| Dehydration | 9/90 (10%) | 1/77 (1.3%) | ||
| Hypocalcemia | 8/90 (8.9%) | 1/77 (1.3%) | ||
| Hypoalbuminemia | 5/90 (5.6%) | 1/77 (1.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Abdominal Pain | 19/90 (21.1%) | 11/77 (14.3%) | ||
| Upper Abdominal Pain | 6/90 (6.7%) | 3/77 (3.9%) | ||
| Arthralgia | 5/90 (5.6%) | 9/77 (11.7%) | ||
| Pain in Extremity | 6/90 (6.7%) | 8/77 (10.4%) | ||
| Back Pain | 5/90 (5.6%) | 7/77 (9.1%) | ||
| Muscle Spasms | 8/90 (8.9%) | 2/77 (2.6%) | ||
| Myalgia | 2/90 (2.2%) | 8/77 (10.4%) | ||
| Muscle Weakness | 5/90 (5.6%) | 3/77 (3.9%) | ||
| Bone Pain | 5/90 (5.6%) | 1/77 (1.3%) | ||
| Musculoskeletal Pain | 0/90 (0%) | 4/77 (5.2%) | ||
| Nervous system disorders | ||||
| Headache | 18/90 (20%) | 9/77 (11.7%) | ||
| Dizziness | 9/90 (10%) | 4/77 (5.2%) | ||
| Neuropathy Peripheral | 3/90 (3.3%) | 9/77 (11.7%) | ||
| Dygeusia | 7/90 (7.8%) | 2/77 (2.6%) | ||
| Seizure | 2/90 (2.2%) | 4/77 (5.2%) | ||
| Psychiatric disorders | ||||
| Insomnia | 8/90 (8.9%) | 5/77 (6.5%) | ||
| Anxiety | 2/90 (2.2%) | 6/77 (7.8%) | ||
| Depression | 6/90 (6.7%) | 2/77 (2.6%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnea | 11/90 (12.2%) | 14/77 (18.2%) | ||
| Cough | 9/90 (10%) | 7/77 (9.1%) | ||
| Oropharyngeal Pain | 5/90 (5.6%) | 1/77 (1.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 10/90 (11.1%) | 9/77 (11.7%) | ||
| Pruritus | 6/90 (6.7%) | 4/77 (5.2%) | ||
| Rash | 3/90 (3.3%) | 5/77 (6.5%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There are restrictions to the PI's rights to discuss or publish trial results.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Nektar Therapeutics |
| Phone | 415-482-5416 |
| medicalaffairs@nektar.com |
- 15-102-14