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

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

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Tumor
• Intervention / Treatment: Drug: NKTR-102 q14d; Drug: NKTR-102 q21d

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium
    • Investigator Site - Gent
  • Leuven, Belgium
    • Investigator Site - Leuven
  • Liege, Belgium
    • Investigator Site - Liege
  • Wilrijk, Belgium
    • Investigator Site - Wilrijk
• United Kingdom
  • Coventry, United Kingdom
    • Investigator Site - Coventry
  • Dundee, United Kingdom, DD1 9SY
    • Investigator Site - Dundee
  • Glasgow, United Kingdom, G12 OYN
    • Investigator Site - Glasgow
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Investigator Site - Newcastle Upon Tyne
  • Northwood
    • Middlesex, Northwood, United Kingdom
      • Investigator Site - Middlesex
• United States
  • California
    • Highland, California, United States, 92346
      • Investigator Site - Higland
    • Los Angeles, California, United States, 90033
      • Investigator Site - Los Angeles
    • Newport Beach, California, United States, 92663
      • Investigator Site - Newport Beach
  • Florida
    • West Palm Beach, Florida, United States, 33401
      • Investigator Site - West Palm Beach
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Investigator Site - Iowa City
  • Michigan
    • Lansing, Michigan, United States, 48912
      • Investigator Site - Lansing
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Investigator Site - Winston-Salem
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73142
      • Investigator Site - Oklahoma City
  • Rhode Island
    • East Providence, Rhode Island, United States, 02915
      • Investigator Site - East Providence
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Investigator Site - Nashville
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Investigator Site - Charlottesville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: NKTR-102 q14d; NKTR-102 given on a q14 day schedule
Experimental: 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.	Drug: NKTR-102 q21d; NKTR-102 given on a q21 day schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST): Primary Efficacy Population	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.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary: Best Overall Response by Gynecologic Cancer Intergroup (GCIG) Criteria: MITT Population	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.	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: Best Overall Response by GCIG Criteria: Primary Efficacy Population	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.	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: Best Overall Response by GCIG Criteria: Platinum-Refractory Population	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.	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: Best Overall Response by GCIG Criteria: Prior PLD Therapy Population	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.	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: Kaplan-Meier Estimate of Progression-Free Survival (PFS): MITT Population	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.	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: Kaplan-Meier Estimate of PFS: Primary Efficacy Population	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.	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: Kaplan-Meier Estimate of PFS: Platinum-Refractory Population	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.	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: Kaplan-Meier Estimate of PFS: Prior PLD Therapy Population	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.	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: Kaplan-Meier Analysis of Duration of Overall Response (DoR): MITT Population	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.	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: Kaplan-Meier Analysis of DoR: Primary Efficacy Population	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.	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: Kaplan-Meier Analysis of DoR: Platinum-Refractory Population	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.	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: Kaplan-Meier Analysis of DoR: Prior PLD Therapy Population	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.	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: CA-125 Response Rate: MITT Population	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.	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: CA-125 Response Rate: Primary Efficacy Population	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.	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: CA-125 Response Rate: Platinum-Refractory Population	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.	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: CA-125 Response Rate: Prior PLD Therapy Population	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.	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: Clinical Benefit Rate: MITT Population	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.	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: Clinical Benefit Rate: Primary Efficacy Population	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.	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: Clinical Benefit Rate: Platinum-Refractory Population	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.	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: Clinical Benefit Rate: Prior PLD Therapy Population	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.	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: Kaplan-Meier Analysis of Overall Survival (OS): MITT Population	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.	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: Kaplan-Meier Analysis of OS: Primary Efficacy Population	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.	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: Kaplan-Meier Analysis of OS: Platinum-Refractory Population	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.	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: Kaplan-Meier Analysis of OS: Prior PLD Therapy Population	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.	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: ORR by RECIST: MITT Population	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.	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: ORR by RECIST: Prior PLD Population	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.	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: ORR by RECIST: Platinum-Refractory Population	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.	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)

Collaborators and Investigators

• Sponsor: Nektar Therapeutics

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: December 4, 2008
• First Submitted That Met QC Criteria: December 9, 2008
• First Posted (Estimate): December 10, 2008

Study Record Updates

• Last Update Posted (Actual): July 12, 2021
• Last Update Submitted That Met QC Criteria: July 9, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etirinotecan pegol
• Other Study ID Numbers: 08-PIR-04