Study to Evaluate the Safety and Efficacy of NKTR-102 in Patients With Metastatic or Locally Advanced Ovarian Cancer

Phase 2

Completed

Conditions: Ovarian Cancer
Tumor

Interventions: Drug: NKTR-102 q14d
Drug: NKTR-102 q21d

Registration Number: NCT00806156

Lead Sponsor: Nektar Therapeutics

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 178

Inclusion Criteria

Histologically or cytologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer
Inoperable metastatic or locally advanced ovarian cancer
Platinum-resistant ovarian cancer defined as progression by RECIST within 6 months of last dose of most recent platinum drug
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.
Diseases must be measurable as defined by RECIST in at least 1 lesion not previously irradiated.
ECOG performance score of 0 or 1.
Adequate organ and bone marrow functions at Screening.

Exclusion Criteria

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
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
Patients who have received CYP3A4 inducers or inhibitors.
Patients who have received any treatment with a camptothecin derivative (eg. irinotecan, topotecan, SN38 investigational agents, etc.).
Patients with CNS metastases.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NKTR-102 q14d	NKTR-102 q14d	NKTR-102 was administered as an intravenous (IV) infusion over 90 ± 10 minutes, on Day 1 of each 2-week \[± 2 days\] cycle at a dose of 170 mg/m\^2 for the first 4 patients enrolled and at a dose of 145 mg/m\^2 for the remainder of the patients.
NKTR-102 q21d	NKTR-102 q21d	NKTR-102 was administered as an IV infusion over 90 ± 10 minutes, on Day 1 of each 3-week \[± 2 days\] cycle at a dose of 170 mg/m\^2 for the first 6 patients enrolled and at a dose of 145 mg/m\^2 for the remainder of the patients.

Primary Outcome Measures

Name	Time	Method
Primary: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST): Primary Efficacy Population	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)	The ORR was defined as the proportion of patients with a complete response (CR) or a partial response (PR) per RECIST 1.0 based upon the best response as assessed by the Investigator. CR was defined by RECIST 1.1 as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to \<10 mm. PR was defined by RECIST 1.1 as at least a 30% decrease in the sum of the diameters (SOD) of target lesions, taking as reference the baseline SOD. The analysis was performed for patients in the Primary Efficacy Population.

Secondary Outcome Measures

Name	Time	Method
Secondary: Best Overall Response by Gynecologic Cancer Intergroup (GCIG) Criteria: MITT Population	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)	Best overall response was defined as the proportion of patients with a CR or a PR as assessed per GCIG criteria. The GCIG proposed the following definition for the date of progression which used both the RECIST and cancer antigen 125 (CA-125) criteria. "A response according to CA-125 has occurred if there is ≥ 50% reduction in CA-125 levels from a pretreatment sample. The response had to be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA-125 only if they had a pretreatment sample that was at least twice the upper limit of normal (ULN) and within 2 weeks prior to starting treatment." Analysis was performed in MITT Population.
Secondary: Best Overall Response by GCIG Criteria: Primary Efficacy Population	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)	Best overall response was defined as the proportion of patients with a CR or a PR per assessed per GCIG criteria. The GCIG proposed the following definition for the date of progression which used both the RECIST and CA-125 criteria. "A response according to CA-125 has occurred if there is ≥ 50% reduction in CA-125 levels from a pretreatment sample. The response had to be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA-125 only if they had a pretreatment sample that was at least twice the ULN and within 2 weeks prior to starting treatment." Analysis was performed in Primary Efficacy Population.
Secondary: Clinical Benefit Rate: Primary Efficacy Population	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)	Clinical benefit rate was calculated as the number of patients with confirmed CR, PR, or SD (where the duration of SD should be ≥ 3 months) by RECIST divided by the total number of measurable patients in the population. Analysis was performed in Primary Efficacy Population.
Secondary: Clinical Benefit Rate: Platinum-Refractory Population	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)	Clinical benefit rate was calculated as the number of patients with confirmed CR, PR, or SD (where the duration of SD should be ≥ 3 months) by RECIST divided by the total number of measurable patients in the population. Analysis was performed in Platinum-Refractory Population.
Secondary: Clinical Benefit Rate: Prior PLD Therapy Population	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)	Clinical benefit rate was calculated as the number of patients with confirmed CR, PR, or SD (where the duration of SD should be ≥ 3 months) by RECIST divided by the total number of measurable patients in the population. Analysis was performed in Prior PLD Therapy Population.
Secondary: Kaplan-Meier Analysis of OS: Platinum-Refractory Population	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)	Duration of OS was defined as the time from the date of randomization to the date of death due to any cause. Patients were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. Patients who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Patients who did not have any follow-up since the date of randomization were censored at the date of randomization. Analysis was performed in Platinum-Refractory Population.
Secondary: ORR by RECIST: Prior PLD Population	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)	The ORR was defined as the proportion of patients with a CR or a PR per RECIST 1.0 based upon the best response as assessed by the Investigator assessment. The analysis was performed for patients in the PLD Population.
Secondary: Best Overall Response by GCIG Criteria: Prior PLD Therapy Population	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)	Best overall response was defined as the proportion of patients with a CR or a PR per assessed per GCIG criteria. The GCIG proposed the following definition for the date of progression which used both the RECIST and CA-125 criteria. "A response according to CA-125 has occurred if there is ≥ 50% reduction in CA-125 levels from a pretreatment sample. The response had to be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA-125 only if they had a pretreatment sample that was at least twice the ULN and within 2 weeks prior to starting treatment." Analysis was performed in Prior PLD Therapy Population.
Secondary: Best Overall Response by GCIG Criteria: Platinum-Refractory Population	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)	Best overall response was defined as the proportion of patients with a CR or a PR per assessed per GCIG criteria. The GCIG proposed the following definition for the date of progression which used both the RECIST and CA-125 criteria. "A response according to CA-125 has occurred if there is ≥ 50% reduction in CA-125 levels from a pretreatment sample. The response had to be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA-125 only if they had a pretreatment sample that was at least twice the ULN and within 2 weeks prior to starting treatment." Analysis was performed in Platinum-Refractory Population.
Secondary: Kaplan-Meier Estimate of Progression-Free Survival (PFS): MITT Population	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)	According to enhanced RECIST 1.1, progressive disease was the appearance of one or more new lesions, OR an unambiguous increase in the sum of target lesion volumes with both 1) \>20% increase in the sum of volumes (SOV) of all target lesions (taking as reference the nadir) and 2) greater than two times the variability of the measurements estimated by the sponsor and/or its designees.
Secondary: Kaplan-Meier Estimate of PFS: Primary Efficacy Population	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)	PFS was defined as the time from the date of the first NKTR-102 administration to the date of PD or death due to any cause. Progressive disease was determined by Investigators using RECIST criteria. Patients who were alive without disease progression at the time of data-cut-off were censored at the time of the last tumor assessment that demonstrated a lack of disease progression (or on Cycle 1 Day 1 if the patient did not undergo repeated imaging while on study). Analysis was performed in Primary Efficacy Population.
Secondary: CA-125 Response Rate: Primary Efficacy Population	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)	CA-125 response was determined by having achieved a ≥50% reduction in serum levels of CA-125 from a pre-treatment level of at least twice the ULN within 2 weeks of starting treatment according to the GCIG criteria. The CA-125 response rate was calculated as the number of patients meeting the endpoint definition divided by the total number of eligible patients per the GCIG criteria for CA-125 in the analysis population. Analysis was performed in Primary Efficacy Population.
Secondary: Kaplan-Meier Estimate of PFS: Platinum-Refractory Population	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)	PFS was defined as the time from the date of the first NKTR-102 administration to the date of PD or death due to any cause. Progressive disease was determined by Investigators using RECIST criteria. Patients who were alive without disease progression at the time of data-cut-off were censored at the time of the last tumor assessment that demonstrated a lack of disease progression (or on Cycle 1 Day 1 if the patient did not undergo repeated imaging while on study). Analysis was performed in Platinum-Refractory Population.
Secondary: Kaplan-Meier Estimate of PFS: Prior PLD Therapy Population	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)	PFS was defined as the time from the date of the first NKTR-102 administration to the date of PD or death due to any cause. Progressive disease was determined by Investigators using RECIST criteria. Patients who were alive without disease progression at the time of data-cut-off were censored at the time of the last tumor assessment that demonstrated a lack of disease progression (or on Cycle 1 Day 1 if the patient did not undergo repeated imaging while on study). Analysis was performed in Prior PLD Population.
Secondary: Kaplan-Meier Analysis of Duration of Overall Response (DoR): MITT Population	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)	DoR was defined as the time from the first documented CR or PR, the date of PD (assessed by central radiological review according to RECIST), or death due to any cause, whichever came first. Patients who were alive without documented PD per RECIST were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease, whichever was earlier. Analysis was performed in MITT Population.
Secondary: Kaplan-Meier Analysis of DoR: Primary Efficacy Population	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)	DoR was defined as the time from the first documented CR or PR, the date of PD (assessed by central radiological review according to RECIST), or death due to any cause, whichever came first. Patients who were alive without documented PD per RECIST were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease, whichever was earlier. Analysis was performed in Primary Efficacy Population.
Secondary: Kaplan-Meier Analysis of DoR: Platinum-Refractory Population	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)	DoR was defined as the time from the first documented CR or PR, the date of PD (assessed by central radiological review according to RECIST), or death due to any cause, whichever came first. Patients who were alive without documented PD per RECIST were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease, whichever was earlier. Analysis was performed in Platinum-Refractory Population.
Secondary: Kaplan-Meier Analysis of DoR: Prior PLD Therapy Population	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)	DoR was defined as the time from the first documented CR or PR, the date of PD (assessed by central radiological review according to RECIST), or death due to any cause, whichever came first. Patients who were alive without documented PD per RECIST were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease, whichever was earlier. Analysis was performed in Prior PLD Therapy Population.
Secondary: CA-125 Response Rate: MITT Population	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)	CA-125 response was determined by having achieved a ≥50% reduction in serum levels of CA-125 from a pre-treatment level of at least twice the ULN within 2 weeks of starting treatment according to the GCIG criteria. The CA-125 response rate was calculated as the number of patients meeting the endpoint definition divided by the total number of eligible patients per the GCIG criteria for CA-125 in the analysis population. Analysis was performed in MITT Population.
Secondary: CA-125 Response Rate: Platinum-Refractory Population	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)	CA-125 response was determined by having achieved a ≥50% reduction in serum levels of CA-125 from a pre-treatment level of at least twice the ULN within 2 weeks of starting treatment according to the GCIG criteria. The CA-125 response rate was calculated as the number of patients meeting the endpoint definition divided by the total number of eligible patients per the GCIG criteria for CA-125 in the analysis population. Analysis was performed in Platinum-Refractory Population.
Secondary: CA-125 Response Rate: Prior PLD Therapy Population	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)	CA-125 response was determined by having achieved a ≥50% reduction in serum levels of CA-125 from a pre-treatment level of at least twice the ULN within 2 weeks of starting treatment according to the GCIG criteria. The CA-125 response rate was calculated as the number of patients meeting the endpoint definition divided by the total number of eligible patients per the GCIG criteria for CA-125 in the analysis population. Analysis was performed in Prior PLD Therapy Population.
Secondary: Clinical Benefit Rate: MITT Population	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)	Clinical benefit rate was calculated as the number of patients with confirmed CR, PR, or SD (where the duration of SD should be ≥ 3 months) by RECIST divided by the total number of measurable patients in the population. Analysis was performed in MITT Population.
Secondary: Kaplan-Meier Analysis of Overall Survival (OS): MITT Population	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)	Duration of OS was defined as the time from the date of randomization to the date of death due to any cause. Patients were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. Patients who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Patients who did not have any follow-up since the date of randomization were censored at the date of randomization. Analysis was performed in MITT Population.
Secondary: Kaplan-Meier Analysis of OS: Primary Efficacy Population	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)	Duration of OS was defined as the time from the date of randomization to the date of death due to any cause. Patients were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. Patients who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Patients who did not have any follow-up since the date of randomization were censored at the date of randomization. Analysis was performed in Primary Efficacy Population.
Secondary: ORR by RECIST: MITT Population	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)	The ORR was defined as the proportion of patients with a CR or a PR per RECIST 1.0 based upon the best response as assessed by the Investigator assessment. The analysis was performed for patients in the MITT Population.
Secondary: ORR by RECIST: Platinum-Refractory Population	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)	The ORR was defined as the proportion of patients with a CR or a PR per RECIST 1.0 based upon the best response as assessed by the Investigator assessment. The analysis was performed for patients in the Platinum-Refractory Population.
Secondary: Kaplan-Meier Analysis of OS: Prior PLD Therapy Population	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)	Duration of OS was defined as the time from the date of randomization to the date of death due to any cause. Patients were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. Patients who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Patients who did not have any follow-up since the date of randomization were censored at the date of randomization. Analysis was performed in Prior PLD Therapy Population.

Trial Locations

Locations (20): Investigator Site - Newcastle Upon Tyne
🇬🇧
Newcastle Upon Tyne, United Kingdom
Investigator Site - Gent
🇧🇪
Gent, Belgium
Investigator Site - Higland
🇺🇸
Highland, California, United States
Investigator Site - Wilrijk
🇧🇪
Wilrijk, Belgium
Investigator Site - Dundee
🇬🇧
Dundee, United Kingdom
Investigator Site - Leuven
🇧🇪
Leuven, Belgium
Investigator Site - Liege
🇧🇪
Liege, Belgium
Investigator Site - Middlesex
🇬🇧
Middlesex, Northwood, United Kingdom
Investigator Site - Glasgow
🇬🇧
Glasgow, United Kingdom
Investigator Site - East Providence
🇺🇸
East Providence, Rhode Island, United States
Investigator Site - Los Angeles
🇺🇸
Los Angeles, California, United States
Investigator Site - Nashville
🇺🇸
Nashville, Tennessee, United States
Investigator Site - Newport Beach
🇺🇸
Newport Beach, California, United States
Investigator Site - West Palm Beach
🇺🇸
West Palm Beach, Florida, United States
Investigator Site - Lansing
🇺🇸
Lansing, Michigan, United States
Investigator Site - Oklahoma City
🇺🇸
Oklahoma City, Oklahoma, United States
Investigator Site - Charlottesville
🇺🇸
Charlottesville, Virginia, United States
Investigator Site - Iowa City
🇺🇸
Iowa City, Iowa, United States
Investigator Site - Coventry
🇬🇧
Coventry, United Kingdom
Investigator Site - Winston-Salem
🇺🇸
Winston-Salem, North Carolina, United States