NCT01696032

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P75+ for phase_2 ovarian-cancer

Timeline
Completed

Started Sep 2012

Typical duration for phase_2 ovarian-cancer

Geographic Reach
3 countries

24 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2012

Completed
25 days until next milestone

First Submitted

Initial submission to the registry

September 26, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 28, 2012

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2016

Completed
4.8 years until next milestone

Results Posted

Study results publicly available

May 25, 2021

Completed
Last Updated

August 27, 2024

Status Verified

July 1, 2024

Enrollment Period

3.9 years

First QC Date

September 26, 2012

Results QC Date

April 30, 2021

Last Update Submit

July 31, 2024

Conditions

Keywords

Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

  • Stage 1: Dose Limiting Toxicities

    Number of participants with dose limiting toxicities (DLTs) in Stage 1

    Up to 12 months

  • 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 Outcomes (9)

  • Objective Response Rate

    Up to 24 months

  • Progression Free Survival at 6 Months

    6 months

  • Clinical Benefit Rate

    Up to 24 months

  • CA-125 Levels

    Up to 24 months

  • Duration of Response

    Up to 24 months

  • +4 more secondary outcomes

Study Arms (2)

SGI-110 + Carboplatin

EXPERIMENTAL

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.

Drug: SGI-110Drug: Carboplatin

SGI-110 + Carboplatin or TC

EXPERIMENTAL

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.

Drug: SGI-110Drug: Treatment of Choice (topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine)Drug: Carboplatin

Interventions

Also known as: guadecitabine
SGI-110 + CarboplatinSGI-110 + Carboplatin or TC

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

SGI-110 + Carboplatin or TC
SGI-110 + CarboplatinSGI-110 + Carboplatin or TC

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (24)

Norris Comprehensive Cancer Center- University of Southern California

Los Angeles, California, 90033, United States

Location

University of Florida Shands Cancer Center

Gainesville, Florida, 32610, United States

Location

Georgia Health Sciences University

Augusta, Georgia, 30912, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Melvin and Bren Simon Cancer Center- Indiana University

Indianapolis, Indiana, 46202, United States

Location

Women's Cancer Care

Covington, Louisiana, 70433, United States

Location

Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland, 21231, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Island Gynecologic Oncology

Brightwaters, New York, 11718, United States

Location

Duke Cancer Institute- Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45267, United States

Location

Mary Crowley Medical Research Center

Dallas, Texas, 75201, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM Gynecologie-Oncologie, Notre Dame Hospital

Montreal, Quebec, H2L 4M1, Canada

Location

Bristol Heamatology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

Location

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

Leeds, LS9 7TF, United Kingdom

Location

Cambridge University Hospitals NHS Foundation and Trust

London, EC1V 4AD, United Kingdom

Location

Univesity College Hospital

London, NW1 2PG, United Kingdom

Location

Imperial College Health Care NHS Trust-Garry Weston Centre

London, W12 0NN, United Kingdom

Location

Mount Vernon Cancer Centre

Middlesex, HA6 2RN, United Kingdom

Location

Royal Marsden Foundation Trust

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (2)

  • 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.

  • 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.

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

guadecitabineTopotecanliposomal doxorubicinPaclitaxelGemcitabineCarboplatin

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Intervention Hierarchy (Ancestors)

CamptothecinAlkaloidsHeterocyclic CompoundsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingCoordination Complexes

Results Point of Contact

Title
Taiho Central
Organization
Taiho Oncology, Inc.

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 26, 2012

First Posted

September 28, 2012

Study Start

September 1, 2012

Primary Completion

August 1, 2016

Study Completion

August 1, 2016

Last Updated

August 27, 2024

Results First Posted

May 25, 2021

Record last verified: 2024-07

Locations