Clinical trial NCT00806156: Study to Evaluate the Safety and Efficacy of NKTR-102 in Patients With Metastatic or Locally Advanced Ovarian Cancer
Official title: A Multicenter, Open-Label, Phase 2 Study to Evaluate the Safety and Efficacy of NKTR-102 When Given on a Q14 Day or a Q21 Day Schedule in Patients With Metastatic or Locally Advanced Platinum-Resistant Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tumor
Ovarian Cancer
Lead sponsor: Nektar Therapeutics
Sponsor class: INDUSTRY
First posted: 2008-12-10
Enrollment: 178
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label, two-arm, 2-stage, Phase 2 study of NKTR-102 in patients with metastatic or locally advanced platinum-resistant ovarian cancer.

Approximately 70 patients will be randomized 1:1 into one of two treatment arms. NKTR-102 will be administered at a dose level of 145 mg/m\^2 in both arms. In Arm A, NKTR-102 will be given on a q14d schedule. In Arm B, NKTR-102 will be given on a q21d schedule. After the initial 70 patients have been enrolled, Arm B will enroll approximately 110 additional patients.


Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer
2. Inoperable metastatic or locally advanced ovarian cancer
3. Platinum-resistant ovarian cancer defined as progression by RECIST within 6 months of last dose of most recent platinum drug
4. Platinum-resistant patients who have progressed after receiving PLD (Doxil/Caelyx)therapy in a platinum-resistant setting or who otherwise unable to receive PLD therapy.
5. Diseases must be measurable as defined by RECIST in at least 1 lesion not previously irradiated.
6. ECOG performance score of 0 or 1.
7. Adequate organ and bone marrow functions at Screening.

Exclusion Criteria:

1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) and have not recovered to NCI-CTCAE grade 1 toxicity prior to Day 1 of Cycle 1
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. Patients who have received CYP3A4 inducers or inhibitors.
4. Patients who have received any treatment with a camptothecin derivative (eg. irinotecan, topotecan, SN38 investigational agents, etc.).
5. Patients with CNS metastases.

Primary outcomes:
measure: Primary: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST): Primary Efficacy Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
Secondary outcomes:
measure: Secondary: Best Overall Response by Gynecologic Cancer Intergroup (GCIG) Criteria: MITT Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Best Overall Response by GCIG Criteria: Primary Efficacy Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Best Overall Response by GCIG Criteria: Platinum-Refractory Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Best Overall Response by GCIG Criteria: Prior PLD Therapy Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Kaplan-Meier Estimate of Progression-Free Survival (PFS): MITT Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Kaplan-Meier Estimate of PFS: Primary Efficacy Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Kaplan-Meier Estimate of PFS: Platinum-Refractory Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Kaplan-Meier Estimate of PFS: Prior PLD Therapy Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Kaplan-Meier Analysis of Duration of Overall Response (DoR): MITT Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Kaplan-Meier Analysis of DoR: Primary Efficacy Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Kaplan-Meier Analysis of DoR: Platinum-Refractory Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Kaplan-Meier Analysis of DoR: Prior PLD Therapy Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: CA-125 Response Rate: MITT Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: CA-125 Response Rate: Primary Efficacy Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: CA-125 Response Rate: Platinum-Refractory Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: CA-125 Response Rate: Prior PLD Therapy Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Clinical Benefit Rate: MITT Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Clinical Benefit Rate: Primary Efficacy Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Clinical Benefit Rate: Platinum-Refractory Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Clinical Benefit Rate: Prior PLD Therapy Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Kaplan-Meier Analysis of Overall Survival (OS): MITT Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Kaplan-Meier Analysis of OS: Primary Efficacy Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Kaplan-Meier Analysis of OS: Platinum-Refractory Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: Kaplan-Meier Analysis of OS: Prior PLD Therapy Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: ORR by RECIST: MITT Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: ORR by RECIST: Prior PLD Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
measure: Secondary: ORR by RECIST: Platinum-Refractory Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
Other outcomes:
Locations:
city: Highland
country: United States
facility: Investigator Site - Higland
state: California
city: Los Angeles
country: United States
facility: Investigator Site - Los Angeles
state: California
city: Newport Beach
country: United States
facility: Investigator Site - Newport Beach
state: California
city: West Palm Beach
country: United States
facility: Investigator Site - West Palm Beach
state: Florida
city: Iowa City
country: United States
facility: Investigator Site - Iowa City
state: Iowa
city: Lansing
country: United States
facility: Investigator Site - Lansing
state: Michigan
city: Winston-Salem
country: United States
facility: Investigator Site - Winston-Salem
state: North Carolina
city: Oklahoma City
country: United States
facility: Investigator Site - Oklahoma City
state: Oklahoma
city: East Providence
country: United States
facility: Investigator Site - East Providence
state: Rhode Island
city: Nashville
country: United States
facility: Investigator Site - Nashville
state: Tennessee
city: Charlottesville
country: United States
facility: Investigator Site - Charlottesville
state: Virginia
city: Gent
country: Belgium
facility: Investigator Site - Gent
city: Leuven
country: Belgium
facility: Investigator Site - Leuven
city: Liege
country: Belgium
facility: Investigator Site - Liege
city: Wilrijk
country: Belgium
facility: Investigator Site - Wilrijk
city: Middlesex
country: United Kingdom
facility: Investigator Site - Middlesex
state: Northwood
city: Coventry
country: United Kingdom
facility: Investigator Site - Coventry
city: Dundee
country: United Kingdom
facility: Investigator Site - Dundee
city: Glasgow
country: United Kingdom
facility: Investigator Site - Glasgow
city: Newcastle Upon Tyne
country: United Kingdom
facility: Investigator Site - Newcastle Upon Tyne
Study officials:
affiliation: Nektar Therapeutics
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Rustin G, Vergote I, Micha JP, Duska LR, Reed N, Bendell J, Spitz D, Dark G, Hoch U, Tagliaferri M, Hannah AL, Garcia AA. A multicenter, open-label, expanded phase 2 study to evaluate the safety and efficacy of etirinotecan pegol, a polymer conjugate of irinotecan, in women with recurrent platinum-resistant or refractory ovarian cancer. Gynecol Oncol. 2017 Nov;147(2):276-282. doi: 10.1016/j.ygyno.2017.08.026. Epub 2017 Sep 19.