SGI-110 in Combination With Carboplatin in Ovarian Cancer

Ovarian Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01696032
• Other study ID #: SGI-110-02
• Status: Completed
• Phase: Phase 2
• Start date: September 2012
• Est. completion date: August 2016

Study information

• Verified date: April 2021
• Source: Astex Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Participants who are women 18 years of age or older.

2. 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.

3. 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.

4. Participants must have had prior paclitaxel treatment.

5. Participants who have measurable disease according to RECIST v1.1 or detectable disease.

6. Participants with ECOG performance status of 0 or 1.

7. Participants with acceptable organ function.

8. Participants must be at least 3 weeks from last chemotherapy.

Exclusion Criteria:

1. Participants who have hypersensitivity to SGI-110 and/or carboplatin or other components of these drug products.

2. Participants who have received prior therapy with any hypomethylating agents.

3. Participants who are refractory to platinum treatment i.e., progressed while on platinum treatment.

4. Participants with abnormal left ventricular ejection fraction.

5. Participants with Grade 2 or greater neuropathy.

6. Participants with known brain metastases.

7. Participants with known history of HIV, HCV or HBV.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• SGI-110

• Treatment of Choice (topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine)
Investigator chose to treat with either topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine
• Carboplatin

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	CHUM Gynecologie-Oncologie, Notre Dame Hospital	Montreal	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
United Kingdom	Bristol Heamatology and Oncology Centre	Bristol
United Kingdom	St. James Univesity Hospital - St. James Institute of Oncology	Leeds
United Kingdom	Cambridge University Hospitals NHS Foundation and Trust	London
United Kingdom	Imperial College Health Care NHS Trust-Garry Weston Centre	London
United Kingdom	Univesity College Hospital	London
United Kingdom	Mount Vernon Cancer Centre	Middlesex
United Kingdom	Royal Marsden Foundation Trust	Sutton
United States	Georgia Health Sciences University	Augusta	Georgia
United States	Johns Hopkins Kimmel Cancer Center	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Island Gynecologic Oncology	Brightwaters	New York
United States	University of Chicago	Chicago	Illinois
United States	University of Cincinnati Cancer Institute	Cincinnati	Ohio
United States	Women's Cancer Care	Covington	Louisiana
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	Duke Cancer Institute- Duke University Medical Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	Melvin and Bren Simon Cancer Center- Indiana University	Indianapolis	Indiana
United States	Norris Comprehensive Cancer Center- University of Southern California	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Astex Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stage 1: Dose Limiting Toxicities	Number of participants with dose limiting toxicities (DLTs) in Stage 1	Up to 12 months
Primary	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.	Up to 24 months
Secondary	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.	Up to 24 months
Secondary	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.	6 months
Secondary	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.	Up to 24 months
Secondary	CA-125 Levels	Percentage of participants with CA-125 reduction by = 50% from baseline	Up to 24 months
Secondary	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.	Up to 24 months
Secondary	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.	Up to 24 months
Secondary	Stage 1: Pharmacokinetic Parameter Cmax	Time to maximum plasma concentration for guadecitabine, decitabine and carboplatin	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)
Secondary	Stage 1: Pharmacokinetic Parameter Tmax	Time to last measurable concentration for guadecitabine, decitabine and carboplatin	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)
Secondary	Stage 1: Pharmacokinetic Parameter AUC0-8	Area under the concentration-time curve from 0 to 8 hours (AUC0-8) for guadecitabine, decitabine and carboplatin	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)