SGI-110 in Combination With Carboplatin in Ovarian Cancer

NCT ID: NCT01696032

Last Updated: 2024-08-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-09-30

Study Completion Date

2016-08-31

Brief Summary

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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.

Detailed Description

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Conditions

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Ovarian Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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SGI-110 + Carboplatin

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.

Group Type EXPERIMENTAL

SGI-110

Intervention Type DRUG

Carboplatin

Intervention Type DRUG

SGI-110 + Carboplatin or TC

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.

Group Type EXPERIMENTAL

SGI-110

Intervention Type DRUG

Treatment of Choice (topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine)

Intervention Type DRUG

Investigator chose to treat with either topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine

Carboplatin

Intervention Type DRUG

Interventions

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SGI-110

Intervention Type DRUG

Treatment of Choice (topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine)

Investigator chose to treat with either topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine

Intervention Type DRUG

Carboplatin

Intervention Type DRUG

Other Intervention Names

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guadecitabine

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Astex Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Norris Comprehensive Cancer Center- University of Southern California

Los Angeles, California, United States

Site Status

University of Florida Shands Cancer Center

Gainesville, Florida, United States

Site Status

Georgia Health Sciences University

Augusta, Georgia, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Melvin and Bren Simon Cancer Center- Indiana University

Indianapolis, Indiana, United States

Site Status

Women's Cancer Care

Covington, Louisiana, United States

Site Status

Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Island Gynecologic Oncology

Brightwaters, New York, United States

Site Status

Duke Cancer Institute- Duke University Medical Center

Durham, North Carolina, United States

Site Status

University of Cincinnati Cancer Institute

Cincinnati, Ohio, United States

Site Status

Mary Crowley Medical Research Center

Dallas, Texas, United States

Site Status

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Site Status

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

CHUM Gynecologie-Oncologie, Notre Dame Hospital

Montreal, Quebec, Canada

Site Status

Bristol Heamatology and Oncology Centre

Bristol, , United Kingdom

Site Status

St. James Univesity Hospital - St. James Institute of Oncology

Leeds, , United Kingdom

Site Status

Cambridge University Hospitals NHS Foundation and Trust

London, , United Kingdom

Site Status

Univesity College Hospital

London, , United Kingdom

Site Status

Imperial College Health Care NHS Trust-Garry Weston Centre

London, , United Kingdom

Site Status

Mount Vernon Cancer Centre

Middlesex, , United Kingdom

Site Status

Royal Marsden Foundation Trust

Sutton, , United Kingdom

Site Status

Countries

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United States Canada United Kingdom

References

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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.

Reference Type DERIVED
PMID: 33289590 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31831561 (View on PubMed)

Other Identifiers

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SGI-110-02

Identifier Type: -

Identifier Source: org_study_id

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