Back to resultsSGI-110 in Combination With Carboplatin in Ovarian Cancer (SGI-110)
Primary Purpose
Ovarian Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SGI-110
Treatment of Choice (topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine)
Carboplatin
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer focused on measuring Ovarian Cancer
Eligibility Criteria
Inclusion Criteria:
- Participants who are women 18 years of age or older.
- Participants who have histologically or cytologically confirmed recurrent high-grade serous epithelial ovarian cancer (Grade 2 or 3), primary peritoneal carcinomatosis or fallopian tube cancer.
- Participants who have platinum-resistant disease (defined as having relapsed within 6 months of her last platinum-containing regimen). There is no limit on the number of prior treatment regimens in Part 1. In Part 2, participants may have had no more than 3 prior cytotoxic treatment regimens, excluding adjuvant or maintenance therapy.
- Participants must have had prior paclitaxel treatment.
- Participants who have measurable disease according to RECIST v1.1 or detectable disease.
- Participants with ECOG performance status of 0 or 1.
- Participants with acceptable organ function.
- Participants must be at least 3 weeks from last chemotherapy.
Exclusion Criteria:
- Participants who have hypersensitivity to SGI-110 and/or carboplatin or other components of these drug products.
- Participants who have received prior therapy with any hypomethylating agents.
- Participants who are refractory to platinum treatment i.e., progressed while on platinum treatment.
- Participants with abnormal left ventricular ejection fraction.
- Participants with Grade 2 or greater neuropathy.
- Participants with known brain metastases.
- Participants with known history of HIV, HCV or HBV.
Sites / Locations
- Norris Comprehensive Cancer Center- University of Southern California
- University of Florida Shands Cancer Center
- Georgia Health Sciences University
- University of Chicago
- Melvin and Bren Simon Cancer Center- Indiana University
- Women's Cancer Care
- Johns Hopkins Kimmel Cancer Center
- Dana Farber Cancer Institute
- Island Gynecologic Oncology
- Duke Cancer Institute- Duke University Medical Center
- University of Cincinnati Cancer Institute
- Mary Crowley Medical Research Center
- Inova Fairfax Hospital
- Tom Baker Cancer Centre
- Juravinski Cancer Centre
- Princess Margaret Hospital
- CHUM Gynecologie-Oncologie, Notre Dame Hospital
- Bristol Heamatology and Oncology Centre
- St. James Univesity Hospital - St. James Institute of Oncology
- Cambridge University Hospitals NHS Foundation and Trust
- Univesity College Hospital
- Imperial College Health Care NHS Trust-Garry Weston Centre
- Mount Vernon Cancer Centre
- Royal Marsden Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
SGI-110 + Carboplatin
SGI-110 + Carboplatin or TC
Arm Description
Stage 1 was a safety lead-in stage with a dose escalation design. Participants were evaluated with the combination of SGI-110 (guadecitabine) plus carboplatin (G+C), given as 28-day treatment cycles: guadecitabine administered subcutaneous (SC) daily on Days 1-5, at a starting dose of 45 mg/m2/day in Cohort 1, followed by carboplatin intravenous (IV) based on a targeted dose of area under the curve (AUC) 5 on Day 8. After dose limiting toxicities were noted, guadecitabine dose was reduced to 30 mg/m2/day for subsequent cycles for 4 participants. Cohort 2 received 30 mg/m2/day guadecitabine and carboplatin IV AUC 4.
Stage 2 was an open-label, randomized, controlled trial. Eligible participants were randomly assigned in a 1:1 ratio to receive either (1) G+C combination treatment in 28-day cycles at 30 mg/m2 SC once daily on Days 1-5 and carboplatin IV AUC 4 on Day 8, or (2) treatment of choice (TC) of topotecan, pegylated liposomal doxorubicin (PLD), paclitaxel, or gemcitabine based on recommended dosing in 28-day cycles; participants initially randomized to TC were able to cross over to receive 30 mg/m2 G+C due to disease progression.
Outcomes
Primary Outcome Measures
Stage 1: Dose Limiting Toxicities
Number of participants with dose limiting toxicities (DLTs) in Stage 1
Stage 2: Progression Free Survival
Progression free survival (PFS) time was defined as the time interval from the date of the first dose of study medication until the earlier of disease progression or death. Participants were treated with their assigned treatment [guadecitabine+carboplatin (G+C) or treatment choice (TC)] until disease progression or unacceptable treatment-related toxicity occurred.
Secondary Outcome Measures
Objective Response Rate
The objective response rate (ORR) was defined as the proportion of participants who experienced an objective response (best overall response of complete response/full response or partial response, which was confirmed by a subsequent assessment at least 28 days later). Response categories were determined based on RECIST v1.1 criteria, or on modified Rustin (CA-125) criteria if response assessment could not be made using RECIST criteria.
Progression Free Survival at 6 Months
Progression free survival rate at 6 months is the proportion of participants who were alive and did not have disease progression at 6 months after start of treatment.
Clinical Benefit Rate
Clinical benefit rate (CBR) was defined as the proportion of subjects who experienced a best overall response of complete response/full response or partial response (confirmed by a subsequent assessment at least 28 days later), or documented stable disease for at least 3 months after the first dose. Response categories were determined based on RECIST v1.1 criteria, then based on modified Rustin (CA-125) criteria if assessment could not be made using RECIST criteria.
CA-125 Levels
Percentage of participants with CA-125 reduction by ≥ 50% from baseline
Duration of Response
Duration of response is defined as the time between the date of the first documentation of complete response/full response or partial response, and the date of disease progression or date of death due to any cause, or the last adequate tumor assessment prior to the start of subsequent anti-cancer therapy including crossing over to G+C from TC arm, whichever occurred earlier. Only participants who responded were included in the duration of response calculation.
Overall Survival
Overall survival was defined as the number of days from the day the participant was administered the first dose of study treatment to the date of death (regardless of cause). Survival time was censored on the last date the participant was known to be alive or lost to follow-up before reaching the event of death; in the TC group, time was censored at the date of crossover.
Stage 1: Pharmacokinetic Parameter Cmax
Time to maximum plasma concentration for guadecitabine, decitabine and carboplatin
Stage 1: Pharmacokinetic Parameter Tmax
Time to last measurable concentration for guadecitabine, decitabine and carboplatin
Stage 1: Pharmacokinetic Parameter AUC0-8
Area under the concentration-time curve from 0 to 8 hours (AUC0-8) for guadecitabine, decitabine and carboplatin
Full Information
NCT ID
NCT01696032
First Posted
September 26, 2012
Last Updated
April 30, 2021
Sponsor
Astex Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01696032
Brief Title
SGI-110 in Combination With Carboplatin in Ovarian Cancer
Acronym
SGI-110
Official Title
A Randomized, Controlled, Open-Label, Phase 2 Trial of SGI-110 and Carboplatin in Subjects With Platinum-Resistant Recurrent Ovarian Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
August 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astex Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
A 2-part, Phase 2 controlled, open-label, randomized study in participants with platinum-resistant recurrent ovarian cancer. In Part 1, participants received SGI-110 and carboplatin. The optimum dose of SGI-110 (guadecitabine) was identified in Part 1 based on safety and efficacy. In Part 2, participants were randomized to receive the dose identified in Part 1 plus carboplatin or one of four treatment of choice at the discretion of the investigator. The treatment of choice consisted of topotecan, pegylated liposomal doxorubicin, paclitaxel or gemcitabine.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
Ovarian Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SGI-110 + Carboplatin
Arm Type
Experimental
Arm Description
Stage 1 was a safety lead-in stage with a dose escalation design. Participants were evaluated with the combination of SGI-110 (guadecitabine) plus carboplatin (G+C), given as 28-day treatment cycles: guadecitabine administered subcutaneous (SC) daily on Days 1-5, at a starting dose of 45 mg/m2/day in Cohort 1, followed by carboplatin intravenous (IV) based on a targeted dose of area under the curve (AUC) 5 on Day 8. After dose limiting toxicities were noted, guadecitabine dose was reduced to 30 mg/m2/day for subsequent cycles for 4 participants. Cohort 2 received 30 mg/m2/day guadecitabine and carboplatin IV AUC 4.
Arm Title
SGI-110 + Carboplatin or TC
Arm Type
Experimental
Arm Description
Stage 2 was an open-label, randomized, controlled trial. Eligible participants were randomly assigned in a 1:1 ratio to receive either (1) G+C combination treatment in 28-day cycles at 30 mg/m2 SC once daily on Days 1-5 and carboplatin IV AUC 4 on Day 8, or (2) treatment of choice (TC) of topotecan, pegylated liposomal doxorubicin (PLD), paclitaxel, or gemcitabine based on recommended dosing in 28-day cycles; participants initially randomized to TC were able to cross over to receive 30 mg/m2 G+C due to disease progression.
Intervention Type
Drug
Intervention Name(s)
SGI-110
Other Intervention Name(s)
guadecitabine
Intervention Type
Drug
Intervention Name(s)
Treatment of Choice (topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine)
Intervention Description
Investigator chose to treat with either topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Primary Outcome Measure Information:
Title
Stage 1: Dose Limiting Toxicities
Description
Number of participants with dose limiting toxicities (DLTs) in Stage 1
Time Frame
Up to 12 months
Title
Stage 2: Progression Free Survival
Description
Progression free survival (PFS) time was defined as the time interval from the date of the first dose of study medication until the earlier of disease progression or death. Participants were treated with their assigned treatment [guadecitabine+carboplatin (G+C) or treatment choice (TC)] until disease progression or unacceptable treatment-related toxicity occurred.
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Objective Response Rate
Description
The objective response rate (ORR) was defined as the proportion of participants who experienced an objective response (best overall response of complete response/full response or partial response, which was confirmed by a subsequent assessment at least 28 days later). Response categories were determined based on RECIST v1.1 criteria, or on modified Rustin (CA-125) criteria if response assessment could not be made using RECIST criteria.
Time Frame
Up to 24 months
Title
Progression Free Survival at 6 Months
Description
Progression free survival rate at 6 months is the proportion of participants who were alive and did not have disease progression at 6 months after start of treatment.
Time Frame
6 months
Title
Clinical Benefit Rate
Description
Clinical benefit rate (CBR) was defined as the proportion of subjects who experienced a best overall response of complete response/full response or partial response (confirmed by a subsequent assessment at least 28 days later), or documented stable disease for at least 3 months after the first dose. Response categories were determined based on RECIST v1.1 criteria, then based on modified Rustin (CA-125) criteria if assessment could not be made using RECIST criteria.
Time Frame
Up to 24 months
Title
CA-125 Levels
Description
Percentage of participants with CA-125 reduction by ≥ 50% from baseline
Time Frame
Up to 24 months
Title
Duration of Response
Description
Duration of response is defined as the time between the date of the first documentation of complete response/full response or partial response, and the date of disease progression or date of death due to any cause, or the last adequate tumor assessment prior to the start of subsequent anti-cancer therapy including crossing over to G+C from TC arm, whichever occurred earlier. Only participants who responded were included in the duration of response calculation.
Time Frame
Up to 24 months
Title
Overall Survival
Description
Overall survival was defined as the number of days from the day the participant was administered the first dose of study treatment to the date of death (regardless of cause). Survival time was censored on the last date the participant was known to be alive or lost to follow-up before reaching the event of death; in the TC group, time was censored at the date of crossover.
Time Frame
Up to 24 months
Title
Stage 1: Pharmacokinetic Parameter Cmax
Description
Time to maximum plasma concentration for guadecitabine, decitabine and carboplatin
Time Frame
Pre-dose and up to 8 hours post-dose on Cycle 1 Day 1 for guadecitabine and decitabine and Day 8 for carboplatin (28 day cycles)
Title
Stage 1: Pharmacokinetic Parameter Tmax
Description
Time to last measurable concentration for guadecitabine, decitabine and carboplatin
Time Frame
Pre-dose and up to 8 hours post-dose on Cycle 1 Day 1 for guadecitabine and decitabine and Day 8 for carboplatin (28 day cycles)
Title
Stage 1: Pharmacokinetic Parameter AUC0-8
Description
Area under the concentration-time curve from 0 to 8 hours (AUC0-8) for guadecitabine, decitabine and carboplatin
Time Frame
Pre-dose and up to 8 hours post-dose on Cycle 1 Day 1 for guadecitabine and decitabine and Day 8 for carboplatin (28 day cycles)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants who are women 18 years of age or older.
Participants who have histologically or cytologically confirmed recurrent high-grade serous epithelial ovarian cancer (Grade 2 or 3), primary peritoneal carcinomatosis or fallopian tube cancer.
Participants who have platinum-resistant disease (defined as having relapsed within 6 months of her last platinum-containing regimen). There is no limit on the number of prior treatment regimens in Part 1. In Part 2, participants may have had no more than 3 prior cytotoxic treatment regimens, excluding adjuvant or maintenance therapy.
Participants must have had prior paclitaxel treatment.
Participants who have measurable disease according to RECIST v1.1 or detectable disease.
Participants with ECOG performance status of 0 or 1.
Participants with acceptable organ function.
Participants must be at least 3 weeks from last chemotherapy.
Exclusion Criteria:
Participants who have hypersensitivity to SGI-110 and/or carboplatin or other components of these drug products.
Participants who have received prior therapy with any hypomethylating agents.
Participants who are refractory to platinum treatment i.e., progressed while on platinum treatment.
Participants with abnormal left ventricular ejection fraction.
Participants with Grade 2 or greater neuropathy.
Participants with known brain metastases.
Participants with known history of HIV, HCV or HBV.
Facility Information:
Facility Name
Norris Comprehensive Cancer Center- University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
University of Florida Shands Cancer Center
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Georgia Health Sciences University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Melvin and Bren Simon Cancer Center- Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Women's Cancer Care
City
Covington
State/Province
Louisiana
ZIP/Postal Code
70433
Country
United States
Facility Name
Johns Hopkins Kimmel Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Island Gynecologic Oncology
City
Brightwaters
State/Province
New York
ZIP/Postal Code
11718
Country
United States
Facility Name
Duke Cancer Institute- Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
University of Cincinnati Cancer Institute
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Mary Crowley Medical Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75201
Country
United States
Facility Name
Inova Fairfax Hospital
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
Tom Baker Cancer Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Juravinski Cancer Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
CHUM Gynecologie-Oncologie, Notre Dame Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4M1
Country
Canada
Facility Name
Bristol Heamatology and Oncology Centre
City
Bristol
ZIP/Postal Code
BS2 8ED
Country
United Kingdom
Facility Name
St. James Univesity Hospital - St. James Institute of Oncology
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Cambridge University Hospitals NHS Foundation and Trust
City
London
ZIP/Postal Code
EC1V 4AD
Country
United Kingdom
Facility Name
Univesity College Hospital
City
London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Facility Name
Imperial College Health Care NHS Trust-Garry Weston Centre
City
London
ZIP/Postal Code
W12 0NN
Country
United Kingdom
Facility Name
Mount Vernon Cancer Centre
City
Middlesex
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
Facility Name
Royal Marsden Foundation Trust
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
33289590
Citation
Cardenas H, Fang F, Jiang G, Perkins SM, Zhang C, Emerson RE, Hutchins G, Keer HN, Liu Y, Matei D, Nephew K. Methylomic Signatures of High Grade Serous Ovarian Cancer. Epigenetics. 2021 Nov;16(11):1201-1216. doi: 10.1080/15592294.2020.1853402. Epub 2020 Dec 8.
Results Reference
derived
PubMed Identifier
31831561
Citation
Oza AM, Matulonis UA, Alvarez Secord A, Nemunaitis J, Roman LD, Blagden SP, Banerjee S, McGuire WP, Ghamande S, Birrer MJ, Fleming GF, Markham MJ, Hirte HW, Provencher DM, Basu B, Kristeleit R, Armstrong DK, Schwartz B, Braly P, Hall GD, Nephew KP, Jueliger S, Oganesian A, Naim S, Hao Y, Keer H, Azab M, Matei D. A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer. Clin Cancer Res. 2020 Mar 1;26(5):1009-1016. doi: 10.1158/1078-0432.CCR-19-1638. Epub 2019 Dec 12.
Results Reference
derived
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SGI-110 in Combination With Carboplatin in Ovarian Cancer
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