A Multicenter, Open-Label, Phase 2 Study to Evaluate the Safety and Efficacy of NKTR-102 (PEG-Irinotecan) When Given on a Q14 Day or a Q21 Day Schedule in Patients with Metastatic Breast Cancer Whose Disease has Failed Prior Taxane-Based Treatment

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2008-005577-36-BE
• Date of registration: 22/01/2009
• Prospective Registration: Yes
• Primary sponsor: Nektar Therapeutics
• Public title: A Multicenter, Open-Label, Phase 2 Study to Evaluate the Safety and Efficacy of NKTR-102 (PEG-Irinotecan) When Given on a Q14 Day or a Q21 Day Schedule in Patients with Metastatic Breast Cancer Whose Disease has Failed Prior Taxane-Based Treatment
• Scientific title: A Multicenter, Open-Label, Phase 2 Study to Evaluate the Safety and Efficacy of NKTR-102 (PEG-Irinotecan) When Given on a Q14 Day or a Q21 Day Schedule in Patients with Metastatic Breast Cancer Whose Disease has Failed Prior Taxane-Based Treatment
• Date of first enrolment: 19/02/2009
• Target sample size: 70
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005577-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, United Kingdom, United States

Contacts

• Name: Regulatory Affairs
• Affiliation: Aptiv Solutions (UK) Ltd

• Name: Regulatory Affairs
• Affiliation: Aptiv Solutions (UK) Ltd

Key inclusion & exclusion criteria

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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 57
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with Metastatic Breast Cancer Whose Disease has Failed Taxane-Based Treatment
MedDRA version: 14.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: PEG-Irinotecan
Product Code: NKTR-102
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Not available
CAS Number: 848779-32-8
Current Sponsor code: NKTR-102
Other descriptive name: PEG-irinotecan
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Primary end point(s): For each schedule:
• Objective response rate as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0

Main Objective: 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)

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.

Secondary Objective: 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

Secondary Outcome(s)

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

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.

Secondary ID(s)

08-PIR-05

Source(s) of Monetary Support

Nektar Therapeutics