E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic or Unresectable Locally Advanced Platinum-Resistant Ovarian Cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Cancer of the female organ (ovaries)
|
|
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 | PT |
E.1.2 | Classification code | 10057529 |
E.1.2 | Term | Ovarian cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 |
For the Primary Efficacy Population:
•To determine the objective response rate (ORR) with NKTR 102 given on a q21d treatment schedule (Arm B) in patients with platinumresistant ovarian cancer and who have received prior PLD therapy in a platinum-resistant setting or who are otherwise unable to receive
further PLD therapy. |
|
E.2.2 | Secondary objectives of the trial |
For each additional patient population:
• To determine the ORR of NKTR-102
For each patient population:
• To estimate duration of response (DoR)
• To estimate progression-free survival (PFS) with NKTR-102
• To estimate overall survival (OS) with NKTR-102
• To determine the clinical benefit rate of NKTR-102
• To determine the cancer antigen 125 (CA-125) response with NKTR-102
• To characterize the safety profile of NKTR-102 |
|
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-year old females
3. Histologically or cytologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer
4. Inoperable metastatic or unresectable locally advanced disease
5. Platinum-resistant ovarian cancer defined as progression by RECIST within 6 months of last dose of most recent platinum drug
6.Platinum-resistant patients who have progressed after receiving PLD
therapy in a platinum-resistant setting or who are otherwise unable to
receive PLD therapy
7. Patients must have measurable disease as defined by RECIST (version 1.0) in at least 1 lesion not previously irradiated
8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
9. 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 × ULN (≤ 5 × ULN if the presence of liver metastasis is confirmed), and
g. Serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 60 mL/min.
10. Women of childbearing potential must have a negative serum pregnancy test at Screening
11. Women 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 study drug treatment period and for at least 8 months after the last dose of the study drug
12. Patients must be able and willing to comply with the study visit schedule and study procedures |
|
E.4 | Principal exclusion criteria |
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 have not recovered to Grade 1 toxicity as defined by NCI-CTCAE version 3.0 (with any grade of alopecia allowed) and Grade 0 diarrhea 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. Minor surgery does not include placement of a venous access device or
simple ascites drain
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 within 2 weeks prior to the first day of study drug treatment
4. Patients who are receiving biologic agents including antibodies (eg, bevacizumab,
trastuzumab, etc.) as well as investigational agents, within 28 days of Cycle 1 Day 1
5. Patients who have received any treatment with a camptothecin derivative (eg, irinotecan, topotecan, SN38 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: early-stage (≤ IB),
low-grade (FIGO Grade 1 or 2) endometrial cancer, non-melanoma skin cancer, or carcinoma in situ of the cervix
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 to other PEGylated drugs
11. Patients with inflammatory bowel disease (eg, Crohn’s disease and ulcerative colitis), unresolved bowel issues (eg, diverticulitis, ileitis, colitis, complete bowel obstruction etc.) or patients with chronic or acute gastrointestinal disorders with diarrhea as a major symptom |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint:
• ORR as determined by RECIST version 1.0, hereafter referred to as RECIST (Therasse et al., 2000) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The End-of-Treatment visit is to occur at 30 ± 3 days after last dose of study drug. Approximately every 3 months following the End-of-Treatment visit, patients will be contacted to assess progression, survival status, receipt of subsequent anti-cancer therapy, and resolution of all toxicity attributable to study drug. Progression during follow-up will only be assessed if the patient did not progress by RECIST (version1.0) during the study drug treatment period and only the first
progression will be reported. Receipt of subsequent anti-cancer therapy will only be assessed until the first anti-cancer therapy is reported. Quarterly follow-up will continue until death, withdrawal by patient, physician decision, lost to follow-up, or study terminated by Sponsor. |
|
E.5.2 | Secondary end point(s) |
Secondary Endpoints:
•Duration of response (DoR)
• Best overall response as determined by Gynecologic Cancer Intergroup
(GCIG) criteria (http://www.gcig.igcs.org/CA-125.html)
• CA-125 response rate as determined by having achieved a ≥ 50% reduction
in serum levels of CA-125 from a pre-treatment level of at least twice the
upper limit of normal (ULN) noted within 2 weeks of starting treatment
according to the GCIG criteria and time to maximum CA-125 response
• Clinical benefit rate (patients with CR, PR, or SD [≥ to 3 months]) by
RECIST (version 1.0)
• PFS
• OS
• 6-month and 1-year survival rate
• Incidence and duration of toxicities, with severity grading according to National Cancer Institute Common Criteria for Adverse Events (NCI-CTCAE) version 3.0 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The End-of-Treatment visit is to occur at 30 ± 3 days after last dose of study drug. Approximately every 3 months following the End-of-Treatment visit, patients will be contacted to assess progression, survival status, receipt of subsequent anti-cancer therapy, and resolution of all toxicity attributable to study drug. Progression during follow-up will only be assessed if the patient did not progress by RECIST (version1.0) during the study drug treatment period and only the first
progression will be reported. Receipt of subsequent anti-cancer therapy will only be assessed until the first anti-cancer therapy is reported. Quarterly follow-up will continue until death, withdrawal by patient, physician decision, lost to follow-up, or study terminated by Sponsor. |
|
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
alternative dosing schedule |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
|
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 |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
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 | 3 |
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 |