E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Metastatic Breast Cancer Whose Disease has Failed Taxane-Based Treatment |
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E.1.1.1 | Medical condition in easily understood language |
Patients with Metastatic Breast Cancer Whose Disease has Failed Taxane-Based Treatment |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the objective response rate (ORR) with NKTR-102 given on one of two schedules: once every 14 days (q14d) and once every 21 days (q21d) |
|
E.2.2 | Secondary objectives of the trial |
For each schedule:
• To estimate progression-free survival (PFS) with NKTR-102
• To evaluate overall survival (OS) rates with NKTR-102
• To characterize the safety profile of NKTR-102 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Each patient must meet the following criteria to be enrolled in this study:
1) Provide signed and dated informed consent prior to study-specific screening procedures
2) ≥ 18 years old
3) Histologically or cytologically confirmed diagnosis of breast cancer
4) Inoperable metastatic disease
5) No more than two prior chemotherapy regimens given in the metastatic setting. Treatment must have included a taxane in the adjuvant or the metastatic setting. The patient may also have received chemotherapy in an adjuvant setting.
6) Measurable disease as defined by RECIST version 1.0 in at least one lesion not previously irradiated.
7) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
8) Patients must have adequate organ and bone marrow function at the screening visit as defined below
a) Absolute neutrophil count ≥ 1,500/mm3 without myeloid growth factor support for 21 days preceding the lab assessment
b) White blood cell (WBC) count ≥ 3,000/mm3 without myeloid growth factor support for 21 days preceding the lab assessment
c) Platelet count ≥ 100,000/mm3, without transfusion within 7 days preceding the lab assessment
d) Hemoglobin ≥ 9 g/dL, without transfusion support
e) Total bilirubin ≤ 2 mg/dL
f) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN) (≤ 5 × ULN if the presence of liver metastasis is confirmed).
g) Serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 60 mL/min
9) Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Cycle 1 Day 1
10) Women of childbearing potential, or men whose female partners are of childbearing potential, must agree to use at least 2 forms of contraception, 1 of which includes a barrier method (male condom) by the male partner, during the treatment period and for at least 8 months after the last dose of the study drug
11) Patients must be able and willing to comply with the study visit schedule and study procedures |
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E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will not be permitted entry to the study:
1) Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to Day 1 of Cycle 1, and must have, as determined by the Investigator, recovered to NCI-CTCAE Grade 1 toxicity (any NCI-CTCAE grade of alopecia is allowed) associated with previous treatments irrespective of the interval from the last treatment
2) Patients who have had any major surgery within 4 weeks prior to Day 1 of Cycle 1 or minor surgery within 2 weeks prior to Day 1 of Cycle 1
3) Administration of any of the following cytochrome P450 3A4 (CYP3A4) inducers or inhibitors: phenytoin, phenobarbital, carbamazepine, rifampin, rifabutin, St. John’s
Wort, ketoconazole, neuromuscular agents or atazanavir sulfate (Section 8.6.2) within
2 weeks prior to the first day of study drug treatment
4) Patients cannot have concomitant use of biologic agents including antibodies (e.g., bevacizumab, trastuzumab, etc.) as well as investigational agents.
5) Patients who have received any treatment with a camptothecin derivative (e.g., irinotecan, topotecan, SN-38 investigational agents, etc.).
6) Known or suspected central nervous system metastases
7) Pregnant or lactating
8) Other malignancy within the past 5 years except for any of the following: nonmelanoma skin cancer, carcinoma in situ of the cervix, or any another malignancy with no evidence of recurrence for more than 5 years. Patients with a history of lowgrade (Gleason score less than or equal to 6) localized prostate cancer will be eligible even if diagnosed less than 5 years previously.
9) Any other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation
10) Patients with a history of hypersensitivity or intolerance to other PEGylated drugs
11) Patients with inflammatory bowel disease (e.g., Crohn’s disease and ulcerative colitis), unresolved bowel issues (e.g., diverticulitis, ileitis, colitis, complete bowel obstruction etc.) or patients with chronic or acute gastrointestinal disorders with diarrhea as a major symptom |
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E.5 End points |
E.5.1 | Primary end point(s) |
For each schedule:
• Objective response rate as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Response duration will be measured from the time measurement criteria for CR/PR (whichever is first recorded) are first met until the first date that recurrent or progressive disease is objectively documented. |
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E.5.2 | Secondary end point(s) |
For each schedule:
• PFS
• OS
• 6-month and 1-yr survival
• Incidence and duration of toxicities, with severity grading according
to National Cancer Institute Common Terminology Criteria for
Adverse Events (NCI-CTCAE) version 3.0 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Progression-free survival is defined as the time from the date of randomization to the date of PD or death from any cause.
Overall survival will be calculated as the time from the date of randomization until death due to any cause. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last visit of last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |