Clinical trial NCT01696032: SGI-110 in Combination With Carboplatin in Ovarian Cancer
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Ovarian Cancer
Lead sponsor: Astex Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2012-09-28
Enrollment: 120
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: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Stage 1: Dose Limiting Toxicities
timeFrame: Up to 12 months
measure: Stage 2: Progression Free Survival
timeFrame: Up to 24 months
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Up to 24 months
measure: Progression Free Survival at 6 Months
timeFrame: 6 months
measure: Clinical Benefit Rate
timeFrame: Up to 24 months
measure: CA-125 Levels
timeFrame: Up to 24 months
measure: Duration of Response
timeFrame: Up to 24 months
measure: Overall Survival
timeFrame: Up to 24 months
measure: Stage 1: Pharmacokinetic Parameter Cmax
timeFrame: 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)
measure: Stage 1: Pharmacokinetic Parameter Tmax
timeFrame: 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)
measure: Stage 1: Pharmacokinetic Parameter AUC0-8
timeFrame: 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)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Norris Comprehensive Cancer Center- University of Southern California
state: California
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Augusta
country: United States
facility: Georgia Health Sciences University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Melvin and Bren Simon Cancer Center- Indiana University
state: Indiana
city: Covington
country: United States
facility: Women's Cancer Care
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Kimmel Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Brightwaters
country: United States
facility: Island Gynecologic Oncology
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute- Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute
state: Ohio
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM Gynecologie-Oncologie, Notre Dame Hospital
state: Quebec
city: Bristol
country: United Kingdom
facility: Bristol Heamatology and Oncology Centre
city: Leeds
country: United Kingdom
facility: St. James Univesity Hospital - St. James Institute of Oncology
city: London
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation and Trust
city: London
country: United Kingdom
facility: Univesity College Hospital
city: London
country: United Kingdom
facility: Imperial College Health Care NHS Trust-Garry Weston Centre
city: Middlesex
country: United Kingdom
facility: Mount Vernon Cancer Centre
city: Sutton
country: United Kingdom
facility: Royal Marsden Foundation Trust
Study officials:
References:
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.
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.