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SGI-110 in Combination With Carboplatin in Ovarian Cancer

Sponsor
Astex Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01696032
Collaborator
(none)
120
Enrollment
24
Locations
2
Arms
47
Duration (Months)
5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Controlled, Open-Label, Phase 2 Trial of SGI-110 and Carboplatin in Subjects With Platinum-Resistant Recurrent Ovarian Cancer
Study Start Date :
Sep 1, 2012
Actual Primary Completion Date :
Aug 1, 2016
Actual Study Completion Date :
Aug 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: SGI-110
Other Names:
  • guadecitabine

    • Drug: Carboplatin
    Experimental: 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.

    Drug: SGI-110
    Other Names:
  • guadecitabine

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

    Drug: Carboplatin

    Outcome Measures

    Primary Outcome Measures

    1. Stage 1: Dose Limiting Toxicities [Up to 12 months]

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

    2. Stage 2: Progression Free Survival [Up to 24 months]

      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

    1. Objective Response Rate [Up to 24 months]

      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.

    2. Progression Free Survival at 6 Months [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.

    3. Clinical Benefit Rate [Up to 24 months]

      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.

    4. CA-125 Levels [Up to 24 months]

      Percentage of participants with CA-125 reduction by ≥ 50% from baseline

    5. Duration of Response [Up to 24 months]

      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.

    6. Overall Survival [Up to 24 months]

      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.

    7. Stage 1: Pharmacokinetic Parameter Cmax [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)]

      Time to maximum plasma concentration for guadecitabine, decitabine and carboplatin

    8. Stage 1: Pharmacokinetic Parameter Tmax [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)]

      Time to last measurable concentration for guadecitabine, decitabine and carboplatin

    9. Stage 1: Pharmacokinetic Parameter AUC0-8 [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)]

      Area under the concentration-time curve from 0 to 8 hours (AUC0-8) for guadecitabine, decitabine and carboplatin

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Norris Comprehensive Cancer Center- University of Southern California Los Angeles California United States 90033
    2 University of Florida Shands Cancer Center Gainesville Florida United States 32610
    3 Georgia Health Sciences University Augusta Georgia United States 30912
    4 University of Chicago Chicago Illinois United States 60637
    5 Melvin and Bren Simon Cancer Center- Indiana University Indianapolis Indiana United States 46202
    6 Women's Cancer Care Covington Louisiana United States 70433
    7 Johns Hopkins Kimmel Cancer Center Baltimore Maryland United States 21231
    8 Dana Farber Cancer Institute Boston Massachusetts United States 02115
    9 Island Gynecologic Oncology Brightwaters New York United States 11718
    10 Duke Cancer Institute- Duke University Medical Center Durham North Carolina United States 27710
    11 University of Cincinnati Cancer Institute Cincinnati Ohio United States 45267
    12 Mary Crowley Medical Research Center Dallas Texas United States 75201
    13 Inova Fairfax Hospital Falls Church Virginia United States 22042
    14 Tom Baker Cancer Centre Calgary Alberta Canada T2N 4N2
    15 Juravinski Cancer Centre Hamilton Ontario Canada L8V 5C2
    16 Princess Margaret Hospital Toronto Ontario Canada M5G 2M9
    17 CHUM Gynecologie-Oncologie, Notre Dame Hospital Montreal Quebec Canada H2L 4M1
    18 Bristol Heamatology and Oncology Centre Bristol United Kingdom BS2 8ED
    19 St. James Univesity Hospital - St. James Institute of Oncology Leeds United Kingdom LS9 7TF
    20 Cambridge University Hospitals NHS Foundation and Trust London United Kingdom EC1V 4AD
    21 Univesity College Hospital London United Kingdom NW1 2PG
    22 Imperial College Health Care NHS Trust-Garry Weston Centre London United Kingdom W12 0NN
    23 Mount Vernon Cancer Centre Middlesex United Kingdom HA6 2RN
    24 Royal Marsden Foundation Trust Sutton United Kingdom SM2 5PT

    Sponsors and Collaborators

    • Astex Pharmaceuticals, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Astex Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT01696032
    Other Study ID Numbers:
    • SGI-110-02
    First Posted:
    Sep 28, 2012
    Last Update Posted:
    May 25, 2021
    Last Verified:
    Apr 1, 2021
    Keywords provided by Astex Pharmaceuticals, Inc.
    Ovarian Cancer
    Additional relevant MeSH terms:
    Ovarian Neoplasms
    Carcinoma, Ovarian Epithelial
    Gemcitabine
    Paclitaxel
    Carboplatin
    Doxorubicin
    Liposomal doxorubicin
    Topotecan
    Guadecitabine

    Study Results

    Participant Flow

    Recruitment Details A total of 124 participants were enrolled in the study and 120 were treated at 20 study centers, with 12 in the United States, 5 in the United Kingdom, and 3 in Canada. The enrollment period was 10 December 2012 (first participant dosed) to 12 May 2014 (last participant first dose).
    Pre-assignment Detail
    Arm/Group Title Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2 Stage 2: Guadecitabine+Carboplatin 30 mg/m2 Stage 2: Treatment Choice
    Arm/Group Description Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants. Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Treatment was selected at the investigator's discretion and administered based on recommended dosing for topotecan (3.5-4.0 mg/m2/wk administered on Days 1, 8, and 15 via IV infusion); pegylated liposomal doxorubicin (PLD) (40-50 mg/m2 administered on Day 1 via IV infusion), paclitaxel (60-80 mg/m2/wk administered on Days 1, 8, 15, and 22 via IV infusion), or gemcitabine (800-1000 mg/m2 administered on Days 1, 8, and 15 via IV infusion). Participants initially randomized to TC were able to cross over to receive 30 mg/m2 G+C due to disease progression.
    Period Title: Overall Study
    STARTED 14 6 51 49
    COMPLETED 0 0 0 27
    NOT COMPLETED 14 6 51 22

    Baseline Characteristics

    Arm/Group Title Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2 Stage 2: Guadecitabine+Carboplatin 30 mg/m2 Stage 2: Treatment Choice Total
    Arm/Group Description Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants. Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Treatment was selected at the investigator's discretion and administered based on recommended dosing for topotecan (3.5-4.0 mg/m2/wk administered on Days 1, 8, and 15 via IV infusion); PLD (40-50 mg/m2 administered on Day 1 via IV infusion), paclitaxel (60-80 mg/m2/wk administered on Days 1, 8, 15, and 22 via IV infusion), or gemcitabine (800-1000 mg/m2 administered on Days 1, 8, and 15 via IV infusion. Participants initially randomized to TC were able to cross over to receive 30 mg/m2 G+C due to disease progression. Total of all reporting groups
    Overall Participants 14 6 51 49 120
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    57.99
    (9.47)
    56.79
    (13.20)
    61.96
    (9.17)
    62.09
    (9.62)
    61.29
    (9.62)
    Sex: Female, Male (Count of Participants)
    Female
    14
    100%
    6
    100%
    51
    100%
    49
    100%
    120
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    7.1%
    0
    0%
    2
    3.9%
    3
    6.1%
    6
    5%
    Not Hispanic or Latino
    13
    92.9%
    6
    100%
    49
    96.1%
    46
    93.9%
    114
    95%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    1
    16.7%
    5
    9.8%
    5
    10.2%
    11
    9.2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    1
    2%
    1
    0.8%
    Black or African American
    1
    7.1%
    0
    0%
    2
    3.9%
    2
    4.1%
    5
    4.2%
    White
    12
    85.7%
    5
    83.3%
    43
    84.3%
    40
    81.6%
    100
    83.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    7.1%
    0
    0%
    1
    2%
    1
    2%
    3
    2.5%

    Outcome Measures

    1. Primary Outcome
    Title Stage 1: Dose Limiting Toxicities
    Description Number of participants with dose limiting toxicities (DLTs) in Stage 1
    Time Frame Up to 12 months

    Outcome Measure Data

    Analysis Population Description
    Safety data set includes data from all participants who received any amount of study drug, including any component of a multi-dose study treatment regimen.
    Arm/Group Title Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2
    Arm/Group Description Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.
    Measure Participants 14 6
    Count of Participants [Participants]
    0
    0%
    4
    66.7%
    2. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Efficacy data set included all participants who received any amount of study drug.
    Arm/Group Title Stage 2: Guadecitabine+Carboplatin 30 mg/m2 Stage 2: Treatment Choice
    Arm/Group Description Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Treatment was selected at the investigator's discretion and administered based on recommended dosing for topotecan (3.5-4.0 mg/m2/wk administered on Days 1, 8, and 15 via IV infusion); PLD (40-50 mg/m2 administered on Day 1 via IV infusion), paclitaxel (60-80 mg/m2/wk administered on Days 1, 8, 15, and 22 via IV infusion), or gemcitabine (800-1000 mg/m2 administered on Days 1, 8, and 15 via IV infusion).
    Measure Participants 51 49
    Median (95% Confidence Interval) [Days]
    114
    64
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Stage 1: Guadecitabine+Carboplatin 30 mg/m2, Stage 1: Guadecitabine+Carboplatin 45 mg/m2
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0654
    Comments
    Method Log Rank
    Comments
    3. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Efficacy data set included all participants who received any amount of study drug.
    Arm/Group Title Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2 Stage 2: Guadecitabine+Carboplatin 30 mg/m2 Stage 2: Treatment Choice Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m2
    Arm/Group Description Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants. Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Treatment was selected at the investigator's discretion and administered based on recommended dosing for topotecan (3.5-4.0 mg/m2/wk administered on Days 1, 8, and 15 via IV infusion); PLD (40-50 mg/m2 administered on Day 1 via IV infusion), paclitaxel (60-80 mg/m2/wk administered on Days 1, 8, 15, and 22 via IV infusion), or gemcitabine (800-1000 mg/m2 administered on Days 1, 8, and 15 via IV infusion). Crossover from treatment choice to the guadecitabine+carboplatin combination treatment arm was permitted for participants after evidence of disease progression.
    Measure Participants 14 6 51 49 27
    Number (95% Confidence Interval) [Percent]
    21
    0
    16
    8
    4
    4. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Efficacy data set included all participants who received any amount of study drug.
    Arm/Group Title Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2 Stage 2: Guadecitabine+Carboplatin 30 mg/m2 Stage 2: Treatment Choice Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m2
    Arm/Group Description Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants. Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Treatment was selected at the investigator's discretion and administered based on recommended dosing for topotecan (3.5-4.0 mg/m2/wk administered on Days 1, 8, and 15 via IV infusion); PLD (40-50 mg/m2 administered on Day 1 via IV infusion), paclitaxel (60-80 mg/m2/wk administered on Days 1, 8, 15, and 22 via IV infusion), or gemcitabine (800-1000 mg/m2 administered on Days 1, 8, and 15 via IV infusion). Crossover from treatment choice to the guadecitabine+carboplatin combination treatment arm was permitted for participants after evidence of disease progression.
    Measure Participants 14 6 51 49 27
    Number (95% Confidence Interval) [Percent of participants]
    0.36
    2.6%
    0.33
    5.5%
    0.37
    0.7%
    0.11
    0.2%
    0.19
    0.2%
    5. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Efficacy data set included all participants who received any amount of study drug.
    Arm/Group Title Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2 Stage 2: Guadecitabine+Carboplatin 30 mg/m2 Stage 2: Treatment Choice Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m2
    Arm/Group Description Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants. Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Treatment was selected at the investigator's discretion and administered based on recommended dosing for topotecan (3.5-4.0 mg/m2/wk administered on Days 1, 8, and 15 via IV infusion); PLD (40-50 mg/m2 administered on Day 1 via IV infusion), paclitaxel (60-80 mg/m2/wk administered on Days 1, 8, 15, and 22 via IV infusion), or gemcitabine (800-1000 mg/m2 administered on Days 1, 8, and 15 via IV infusion). Crossover from treatment choice to the guadecitabine+carboplatin combination treatment arm was permitted for participants after evidence of disease progression.
    Measure Participants 14 6 51 49 27
    Number (95% Confidence Interval) [Percent of participants]
    43
    307.1%
    50
    833.3%
    41
    80.4%
    29
    59.2%
    19
    15.8%
    6. Secondary Outcome
    Title CA-125 Levels
    Description Percentage of participants with CA-125 reduction by ≥ 50% from baseline
    Time Frame Up to 24 months

    Outcome Measure Data

    Analysis Population Description
    Efficacy data set included all participants who received any amount of study drug.
    Arm/Group Title Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2 Stage 2: Guadecitabine+Carboplatin 30 mg/m2 Stage 2: Treatment Choice Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m2
    Arm/Group Description Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants. Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Treatment was selected at the investigator's discretion and administered based on recommended dosing for topotecan (3.5-4.0 mg/m2/wk administered on Days 1, 8, and 15 via IV infusion); PLD (40-50 mg/m2 administered on Day 1 via IV infusion), paclitaxel (60-80 mg/m2/wk administered on Days 1, 8, 15, and 22 via IV infusion), or gemcitabine (800-1000 mg/m2 administered on Days 1, 8, and 15 via IV infusion). Crossover from treatment choice to the guadecitabine+carboplatin combination treatment arm was permitted for participants after evidence of disease progression.
    Measure Participants 14 6 51 49 27
    Number (95% Confidence Interval) [Percent of participants]
    27
    192.9%
    50
    833.3%
    36
    70.6%
    32
    65.3%
    29
    24.2%
    7. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Efficacy data set included all participants who received any amount of study drug.
    Arm/Group Title Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2 Stage 2: Guadecitabine+Carboplatin 30 mg/m2 Stage 2: Treatment Choice Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m2
    Arm/Group Description Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants. Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Treatment was selected at the investigator's discretion and administered based on recommended dosing for topotecan (3.5-4.0 mg/m2/wk administered on Days 1, 8, and 15 via IV infusion); PLD (40-50 mg/m2 administered on Day 1 via IV infusion), paclitaxel (60-80 mg/m2/wk administered on Days 1, 8, 15, and 22 via IV infusion), or gemcitabine (800-1000 mg/m2 administered on Days 1, 8, and 15 via IV infusion). Crossover from treatment choice to the guadecitabine+carboplatin combination treatment arm was permitted for participants after evidence of disease progression.
    Measure Participants 6 3 21 14 5
    Median (95% Confidence Interval) [Days]
    225
    195
    186
    173
    182
    8. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Efficacy data set included all participants who received any amount of study drug.
    Arm/Group Title Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2 Stage 2: Guadecitabine+Carboplatin 30 mg/m2 Stage 2: Treatment Choice Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m2
    Arm/Group Description Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants. Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Treatment was selected at the investigator's discretion and administered based on recommended dosing for topotecan (3.5-4.0 mg/m2/wk administered on Days 1, 8, and 15 via IV infusion); PLD (40-50 mg/m2 administered on Day 1 via IV infusion), paclitaxel (60-80 mg/m2/wk administered on Days 1, 8, 15, and 22 via IV infusion), or gemcitabine (800-1000 mg/m2 administered on Days 1, 8, and 15 via IV infusion). Crossover from treatment choice to the guadecitabine+carboplatin combination treatment arm was permitted for participants after evidence of disease progression.
    Measure Participants 14 6 51 49 27
    Median (95% Confidence Interval) [Days]
    341
    195
    331
    221
    279
    9. Secondary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic (PK) population included participants for which sufficient data were available to calculate PK parameters.
    Arm/Group Title Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2
    Arm/Group Description Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.
    Measure Participants 14 5
    Guadecitabine
    96.2
    (78.3)
    109
    (70.8)
    Decitabine
    22.6
    (13.3)
    26.3
    (14.5)
    Carboplatin
    19600
    (5650)
    21900
    (13800)
    10. Secondary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic (PK) population included participants for which sufficient data were available to calculate PK parameters.
    Arm/Group Title Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2
    Arm/Group Description Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.
    Measure Participants 14 5
    Guadecitabine
    1.42
    1.98
    Decitabine
    1.98
    3.95
    Carboplatin
    1.03
    1.05
    11. Secondary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic (PK) population included participants for which sufficient data were available to calculate PK parameters.
    Arm/Group Title Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2
    Arm/Group Description Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.
    Measure Participants 13 4
    Guadecitabine
    239
    (136)
    416
    (217)
    Decitabine
    71.1
    (26.6)
    129
    (17.9)
    Carboplatin
    51200
    (12100)
    41900
    (31700)

    Adverse Events

    Time Frame Approximately 4 years
    Adverse Event Reporting Description Treatment-emergent adverse events (TEAEs) were defined as events that first occurred or worsened after the first dose of study drug given on Cycle 1 Day 1 until 30 days after the last dose of study treatment.
    Arm/Group Title Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2 Stage 2: Guadecitabine+Carboplatin 30 mg/m2 Stage 2: Treatment Choice Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m2
    Arm/Group Description Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants. Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Treatment was selected at the investigator's discretion and administered based on recommended dosing for topotecan (3.5-4.0 mg/m2/wk administered on Days 1, 8, and 15 via IV infusion); PLD (40-50 mg/m2 administered on Day 1 via IV infusion), paclitaxel (60-80 mg/m2/wk administered on Days 1, 8, 15, and 22 via IV infusion), or gemcitabine (800-1000 mg/m2 administered on Days 1, 8, and 15 via IV infusion). Crossover from treatment choice to the guadecitabine+carboplatin combination treatment arm was permitted for participants after evidence of disease progression.
    All Cause Mortality
    Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2 Stage 2: Guadecitabine+Carboplatin 30 mg/m2 Stage 2: Treatment Choice Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 14/14 (100%) 4/6 (66.7%) 43/51 (84.3%) 18/49 (36.7%) 22/27 (81.5%)
    Serious Adverse Events
    Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2 Stage 2: Guadecitabine+Carboplatin 30 mg/m2 Stage 2: Treatment Choice Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/14 (57.1%) 4/6 (66.7%) 26/51 (51%) 24/49 (49%) 12/27 (44.4%)
    Blood and lymphatic system disorders
    Febrile neutropenia 1/14 (7.1%) 1 0/6 (0%) 0 1/51 (2%) 1 0/49 (0%) 0 3/27 (11.1%) 3
    Neutropenia 1/14 (7.1%) 1 2/6 (33.3%) 2 1/51 (2%) 1 0/49 (0%) 0 1/27 (3.7%) 1
    Anemia 0/14 (0%) 0 1/6 (16.7%) 1 1/51 (2%) 1 1/49 (2%) 1 0/27 (0%) 0
    Leukopenia 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 1/27 (3.7%) 1
    Pancytopenia 0/14 (0%) 0 0/6 (0%) 0 1/51 (2%) 1 0/49 (0%) 0 0/27 (0%) 0
    Thrombocytopenia 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Cardiac disorders
    Pericardial effusion 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Sinus tachycardia 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Gastrointestinal disorders
    Small intestinal obstruction 2/14 (14.3%) 2 0/6 (0%) 0 8/51 (15.7%) 8 4/49 (8.2%) 4 1/27 (3.7%) 1
    Abdominal pain 0/14 (0%) 0 0/6 (0%) 0 2/51 (3.9%) 2 3/49 (6.1%) 3 5/27 (18.5%) 5
    Vomiting 2/14 (14.3%) 2 2/6 (33.3%) 2 1/51 (2%) 1 5/49 (10.2%) 5 2/27 (7.4%) 2
    Nausea 2/14 (14.3%) 2 2/6 (33.3%) 2 0/51 (0%) 0 2/49 (4.1%) 2 1/27 (3.7%) 1
    Intestinal obstruction 0/14 (0%) 0 0/6 (0%) 0 4/51 (7.8%) 4 4/49 (8.2%) 4 0/27 (0%) 0
    Constipation 2/14 (14.3%) 2 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 1/27 (3.7%) 1
    Ascites 0/14 (0%) 0 0/6 (0%) 0 2/51 (3.9%) 2 2/49 (4.1%) 2 0/27 (0%) 0
    Diarrhea 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 1/27 (3.7%) 1
    Gastrointestinal hemorrhage 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 1/27 (3.7%) 1
    Large intestine perforation 0/14 (0%) 0 0/6 (0%) 0 1/51 (2%) 1 0/49 (0%) 0 0/27 (0%) 0
    Intestinal perforation 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Abdominal abscess 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    General disorders
    Pyrexia 0/14 (0%) 0 0/6 (0%) 0 2/51 (3.9%) 2 0/49 (0%) 0 1/27 (3.7%) 1
    Adverse drug reaction 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Asthenia 0/14 (0%) 0 0/6 (0%) 0 1/51 (2%) 1 0/49 (0%) 0 0/27 (0%) 0
    Fatigue 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 1/27 (3.7%) 1
    Influenza like illness 0/14 (0%) 0 0/6 (0%) 0 1/51 (2%) 1 0/49 (0%) 0 0/27 (0%) 0
    Pain 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Elective procedure 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 1/27 (3.7%) 1
    Hepatobiliary disorders
    Cholelithiasis 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Portal vein thrombosis 0/14 (0%) 0 0/6 (0%) 0 1/51 (2%) 1 0/49 (0%) 0 0/27 (0%) 0
    Immune system disorders
    Anaphylactic reaction 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 1/27 (3.7%) 1
    Infections and infestations
    Sepsis 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 2/49 (4.1%) 2 3/27 (11.1%) 3
    Pneumonia 0/14 (0%) 0 1/6 (16.7%) 1 1/51 (2%) 1 2/49 (4.1%) 2 0/27 (0%) 0
    Cellulitis 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Infection 0/14 (0%) 0 0/6 (0%) 0 1/51 (2%) 1 0/49 (0%) 0 0/27 (0%) 0
    Lower respiratory tract infections 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Urinary tract infection 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Postoperative fever 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Investigations
    International normalized ratio increased 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Transaminases increased 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Metabolism and nutrition disorders
    Dehydration 0/14 (0%) 0 0/6 (0%) 0 2/51 (3.9%) 2 2/49 (4.1%) 2 0/27 (0%) 0
    Failure to thrive 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Hyponatremia 0/14 (0%) 0 0/6 (0%) 0 1/51 (2%) 1 0/49 (0%) 0 0/27 (0%) 0
    Decreased appetite 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Musculoskeletal and connective tissue disorders
    Gait disturbance 0/14 (0%) 0 0/6 (0%) 0 1/51 (2%) 1 0/49 (0%) 0 0/27 (0%) 0
    Pain in jaw 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 1/27 (3.7%) 1
    Musculoskeletal chest pain 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Nervous system disorders
    Cerebrovascular accident 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Seizure 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Peripheral neuropathy sensory 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Radicular pain 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Psychiatric disorders
    Mental status change 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Renal and urinary disorders
    Renal failure 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 2/49 (4.1%) 2 0/27 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 1/14 (7.1%) 1 0/6 (0%) 0 3/51 (5.9%) 3 3/49 (6.1%) 3 0/27 (0%) 0
    Pulmonary embolism 1/14 (7.1%) 1 1/6 (16.7%) 1 0/51 (0%) 0 2/49 (4.1%) 2 1/27 (3.7%) 1
    Dyspnea 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 1/27 (3.7%) 1
    Pulmonary edema 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Skin and subcutaneous tissue disorders
    Pyoderma gangrenosum 0/14 (0%) 0 0/6 (0%) 0 1/51 (2%) 1 0/49 (0%) 0 0/27 (0%) 0
    Vascular disorders
    Hypotension 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Other (Not Including Serious) Adverse Events
    Stage 1: Guadecitabine+Carboplatin 30 mg/m2 Stage 1: Guadecitabine+Carboplatin 45 mg/m2 Stage 2: Guadecitabine+Carboplatin 30 mg/m2 Stage 2: Treatment Choice Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 14/14 (100%) 6/6 (100%) 50/51 (98%) 49/49 (100%) 27/27 (100%)
    Blood and lymphatic system disorders
    Neutropenia 7/14 (50%) 7 5/6 (83.3%) 5 36/51 (70.6%) 36 16/49 (32.7%) 16 18/27 (66.7%) 18
    Leukopenia 5/14 (35.7%) 5 2/6 (33.3%) 2 16/51 (31.4%) 16 11/49 (22.4%) 11 12/27 (44.4%) 12
    Anemia 7/14 (50%) 7 4/6 (66.7%) 4 16/51 (31.4%) 16 25/49 (51%) 25 8/27 (29.6%) 8
    Thrombocytopenia 3/14 (21.4%) 3 6/6 (100%) 6 12/51 (23.5%) 12 12/49 (24.5%) 12 10/27 (37%) 10
    Pancytopenia 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Cardiac disorders
    Palpitations 0/14 (0%) 0 0/6 (0%) 0 4/51 (7.8%) 4 0/49 (0%) 0 1/27 (3.7%) 1
    Sinus tachycardia 1/14 (7.1%) 1 0/6 (0%) 0 1/51 (2%) 1 1/49 (2%) 1 1/27 (3.7%) 1
    Ear and labyrinth disorders
    Ear discomfort 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 1/27 (3.7%) 1
    Ear pain 1/14 (7.1%) 1 0/6 (0%) 0 1/51 (2%) 1 0/49 (0%) 0 0/27 (0%) 0
    Gastrointestinal disorders
    Nausea 10/14 (71.4%) 10 2/6 (33.3%) 2 38/51 (74.5%) 38 28/49 (57.1%) 28 12/27 (44.4%) 12
    Vomiting 6/14 (42.9%) 6 2/6 (33.3%) 2 32/51 (62.7%) 32 15/49 (30.6%) 15 10/27 (37%) 10
    Constipation 5/14 (35.7%) 5 4/6 (66.7%) 4 22/51 (43.1%) 22 17/49 (34.7%) 17 10/27 (37%) 10
    Abdominal pain 4/14 (28.6%) 4 2/6 (33.3%) 2 21/51 (41.2%) 21 17/49 (34.7%) 17 8/27 (29.6%) 8
    Diarrhea 4/14 (28.6%) 4 1/6 (16.7%) 1 21/51 (41.2%) 21 11/49 (22.4%) 11 9/27 (33.3%) 9
    Stomatitis 3/14 (21.4%) 3 1/6 (16.7%) 1 11/51 (21.6%) 11 12/49 (24.5%) 12 2/27 (7.4%) 2
    Abdominal distension 1/14 (7.1%) 1 0/6 (0%) 0 10/51 (19.6%) 10 12/49 (24.5%) 12 4/27 (14.8%) 4
    Dyspepsia 3/14 (21.4%) 3 2/6 (33.3%) 2 6/51 (11.8%) 6 10/49 (20.4%) 10 3/27 (11.1%) 3
    Ascites 2/14 (14.3%) 2 2/6 (33.3%) 2 4/51 (7.8%) 4 4/49 (8.2%) 4 2/27 (7.4%) 2
    Gastroesophageal reflux disease 1/14 (7.1%) 1 2/6 (33.3%) 2 8/51 (15.7%) 8 4/49 (8.2%) 4 1/27 (3.7%) 1
    Abdominal pain upper 3/14 (21.4%) 3 0/6 (0%) 0 4/51 (7.8%) 4 5/49 (10.2%) 5 3/27 (11.1%) 3
    Abdominal discomfort 0/14 (0%) 0 0/6 (0%) 0 3/51 (5.9%) 3 2/49 (4.1%) 2 1/27 (3.7%) 1
    Abdominal pain lower 0/14 (0%) 0 0/6 (0%) 0 3/51 (5.9%) 3 1/49 (2%) 1 3/27 (11.1%) 3
    Anorectal discomfort 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Dry mouth 1/14 (7.1%) 1 2/6 (33.3%) 2 1/51 (2%) 1 4/49 (8.2%) 4 2/27 (7.4%) 2
    Flatulence 0/14 (0%) 0 0/6 (0%) 0 4/51 (7.8%) 4 2/49 (4.1%) 2 2/27 (7.4%) 2
    Hemorrhoids 0/14 (0%) 0 0/6 (0%) 0 1/51 (2%) 1 3/49 (6.1%) 3 0/27 (0%) 0
    Proctalgia 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 2/27 (7.4%) 2
    Toothache 1/14 (7.1%) 1 0/6 (0%) 0 1/51 (2%) 1 1/49 (2%) 1 2/27 (7.4%) 2
    Dental caries 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 1/27 (3.7%) 1
    Epigastric discomfort 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Gastrointestinal hemorrhage 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Lip dry 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Oral pain 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Rectal hemorrhage 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 1/27 (3.7%) 1
    Dysphagia 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 3/49 (6.1%) 3 0/27 (0%) 0
    General disorders
    Fatigue 9/14 (64.3%) 9 4/6 (66.7%) 4 33/51 (64.7%) 33 26/49 (53.1%) 26 14/27 (51.9%) 14
    Injection site reaction 8/14 (57.1%) 8 2/6 (33.3%) 2 23/51 (45.1%) 23 1/49 (2%) 1 9/27 (33.3%) 9
    Pyrexia 2/14 (14.3%) 2 4/6 (66.7%) 4 8/51 (15.7%) 8 3/49 (6.1%) 3 3/27 (11.1%) 3
    Peripheral edema 2/14 (14.3%) 2 2/6 (33.3%) 2 5/51 (9.8%) 5 14/49 (28.6%) 14 3/27 (11.1%) 3
    Adverse drug reaction 3/14 (21.4%) 3 1/6 (16.7%) 1 2/51 (3.9%) 2 0/49 (0%) 0 4/27 (14.8%) 4
    Pain 0/14 (0%) 0 0/6 (0%) 0 5/51 (9.8%) 5 4/49 (8.2%) 4 1/27 (3.7%) 1
    Chills 0/14 (0%) 0 0/6 (0%) 0 4/51 (7.8%) 4 2/49 (4.1%) 2 1/27 (3.7%) 1
    Hernia pain 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Malaise 0/14 (0%) 0 0/6 (0%) 0 3/51 (5.9%) 3 1/49 (2%) 1 1/27 (3.7%) 1
    Peripheral swelling 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 3/49 (6.1%) 3 0/27 (0%) 0
    Early satiety 0/14 (0%) 0 0/6 (0%) 0 4/51 (7.8%) 4 2/49 (4.1%) 2 1/27 (3.7%) 1
    Asthenia 0/14 (0%) 0 1/6 (16.7%) 1 1/51 (2%) 1 2/49 (4.1%) 2 0/27 (0%) 0
    Injection site pain 4/14 (28.6%) 4 0/6 (0%) 0 1/51 (2%) 1 0/49 (0%) 0 0/27 (0%) 0
    Mass 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Immune system disorders
    Drug hypersensitivity 2/14 (14.3%) 2 1/6 (16.7%) 1 3/51 (5.9%) 3 0/49 (0%) 0 0/27 (0%) 0
    Infections and infestations
    Bacteriuria 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Breast cellulitis 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Localized infection 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 2/49 (4.1%) 2 0/27 (0%) 0
    Nasopharyngitis 0/14 (0%) 0 0/6 (0%) 0 1/51 (2%) 1 2/49 (4.1%) 2 2/27 (7.4%) 2
    Rhinitis 0/14 (0%) 0 0/6 (0%) 0 3/51 (5.9%) 3 0/49 (0%) 0 0/27 (0%) 0
    Rocky mountain spotted fever 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Urinary tract infection 2/14 (14.3%) 2 1/6 (16.7%) 1 8/51 (15.7%) 8 4/49 (8.2%) 4 3/27 (11.1%) 3
    Vaginitis bacterial 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Clostridium difficile colitis 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 1/27 (3.7%) 1
    Enterococcal infection 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Impetigo 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Oral candidiasis 0/14 (0%) 0 1/6 (16.7%) 1 1/51 (2%) 1 2/49 (4.1%) 2 0/27 (0%) 0
    Injury, poisoning and procedural complications
    Contusion 1/14 (7.1%) 1 0/6 (0%) 0 2/51 (3.9%) 2 0/49 (0%) 0 0/27 (0%) 0
    Infusion related reaction 2/14 (14.3%) 2 2/6 (33.3%) 2 3/51 (5.9%) 3 0/49 (0%) 0 2/27 (7.4%) 2
    Procedural pain 1/14 (7.1%) 1 0/6 (0%) 0 3/51 (5.9%) 3 1/49 (2%) 1 0/27 (0%) 0
    Skin abrasion 0/14 (0%) 0 0/6 (0%) 0 3/51 (5.9%) 3 0/49 (0%) 0 0/27 (0%) 0
    Stoma site pain 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Investigations
    Weight decreased 1/14 (7.1%) 1 0/6 (0%) 0 2/51 (3.9%) 2 5/49 (10.2%) 5 0/27 (0%) 0
    Anion gap increased 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Aspartate aminotransferase 2/14 (14.3%) 2 0/6 (0%) 0 4/51 (7.8%) 4 2/49 (4.1%) 2 2/27 (7.4%) 2
    Bilirubin urine present 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Blood albumin decreased 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Blood alkaline phosphatase increased 2/14 (14.3%) 2 0/6 (0%) 0 2/51 (3.9%) 2 4/49 (8.2%) 4 1/27 (3.7%) 1
    Blood chloride decreased 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Blood lactate dehydrogenase increased 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Carbon dioxide decreased 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Protein urine present 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Weight increased 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Alanine aminotransferase increased 2/14 (14.3%) 2 1/6 (16.7%) 1 3/51 (5.9%) 3 2/49 (4.1%) 2 2/27 (7.4%) 2
    Specific gravity urine increased 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Urine ketone body present 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Urine leukocyte esterase positive 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Blood bilirubin increased 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Blood phosphorous decreased 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Protein total decreased 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Blood creatinine increased 0/14 (0%) 0 1/6 (16.7%) 1 7/51 (13.7%) 7 3/49 (6.1%) 3 2/27 (7.4%) 2
    International normalized ratio increased 0/14 (0%) 0 1/6 (16.7%) 1 1/51 (2%) 1 0/49 (0%) 0 0/27 (0%) 0
    Metabolism and nutrition disorders
    Hypomagnesemia 3/14 (21.4%) 3 4/6 (66.7%) 4 15/51 (29.4%) 15 8/49 (16.3%) 8 9/27 (33.3%) 9
    Decreased appetite 6/14 (42.9%) 6 2/6 (33.3%) 2 14/51 (27.5%) 14 13/49 (26.5%) 13 6/27 (22.2%) 6
    Hypokalemia 3/14 (21.4%) 3 2/6 (33.3%) 2 6/51 (11.8%) 6 8/49 (16.3%) 8 3/27 (11.1%) 3
    Hyponatremia 3/14 (21.4%) 3 1/6 (16.7%) 1 3/51 (5.9%) 3 7/49 (14.3%) 7 1/27 (3.7%) 1
    Dehydration 1/14 (7.1%) 1 1/6 (16.7%) 1 4/51 (7.8%) 4 6/49 (12.2%) 6 5/27 (18.5%) 5
    Hyperglycemia 1/14 (7.1%) 1 1/6 (16.7%) 1 1/51 (2%) 1 1/49 (2%) 1 0/27 (0%) 0
    Hypoalbuminemia 0/14 (0%) 0 1/6 (16.7%) 1 1/51 (2%) 1 3/49 (6.1%) 3 3/27 (11.1%) 3
    Hypocalcemia 1/14 (7.1%) 1 1/6 (16.7%) 1 2/51 (3.9%) 2 2/49 (4.1%) 2 1/27 (3.7%) 1
    Hypoglycemia 2/14 (14.3%) 2 0/6 (0%) 0 0/51 (0%) 0 2/49 (4.1%) 2 0/27 (0%) 0
    Hypophosphatemia 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 2/49 (4.1%) 2 0/27 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 3/14 (21.4%) 3 1/6 (16.7%) 1 9/51 (17.6%) 9 8/49 (16.3%) 8 5/27 (18.5%) 5
    Arthralgia 2/14 (14.3%) 2 0/6 (0%) 0 11/51 (21.6%) 11 6/49 (12.2%) 6 2/27 (7.4%) 2
    Pain in extremity 0/14 (0%) 0 1/6 (16.7%) 1 10/51 (19.6%) 10 8/49 (16.3%) 8 3/27 (11.1%) 3
    Flank pain 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 3/27 (11.1%) 3
    Groin pain 1/14 (7.1%) 1 0/6 (0%) 0 2/51 (3.9%) 2 1/49 (2%) 1 3/27 (11.1%) 3
    Joint stiffness 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Muscle spasms 1/14 (7.1%) 1 0/6 (0%) 0 5/51 (9.8%) 5 4/49 (8.2%) 4 3/27 (11.1%) 3
    Muscular weakness 2/14 (14.3%) 2 1/6 (16.7%) 1 3/51 (5.9%) 3 1/49 (2%) 1 0/27 (0%) 0
    Musculoskeletal pain 1/14 (7.1%) 1 0/6 (0%) 0 6/51 (11.8%) 6 0/49 (0%) 0 0/27 (0%) 0
    Musculoskeletal chest pain 1/14 (7.1%) 1 0/6 (0%) 0 5/51 (9.8%) 5 2/49 (4.1%) 2 1/27 (3.7%) 1
    Myalgia 2/14 (14.3%) 2 0/6 (0%) 0 3/51 (5.9%) 3 3/49 (6.1%) 3 2/27 (7.4%) 2
    Neck pain 0/14 (0%) 0 0/6 (0%) 0 1/51 (2%) 1 1/49 (2%) 1 2/27 (7.4%) 2
    Bone pain 3/14 (21.4%) 3 0/6 (0%) 0 1/51 (2%) 1 0/49 (0%) 0 0/27 (0%) 0
    Nervous system disorders
    Headache 3/14 (21.4%) 3 0/6 (0%) 0 9/51 (17.6%) 9 5/49 (10.2%) 5 1/27 (3.7%) 1
    Dizziness 1/14 (7.1%) 1 0/6 (0%) 0 5/51 (9.8%) 5 6/49 (12.2%) 6 1/27 (3.7%) 1
    Dysgeusia 0/14 (0%) 0 0/6 (0%) 0 4/51 (7.8%) 4 2/49 (4.1%) 2 1/27 (3.7%) 1
    Neuropathy peripheral 0/14 (0%) 0 0/6 (0%) 0 3/51 (5.9%) 3 4/49 (8.2%) 4 0/27 (0%) 0
    Parasthesia 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Tremor 1/14 (7.1%) 1 0/6 (0%) 0 1/51 (2%) 1 1/49 (2%) 1 0/27 (0%) 0
    Psychiatric disorders
    Anxiety 3/14 (21.4%) 3 2/6 (33.3%) 2 6/51 (11.8%) 6 6/49 (12.2%) 6 1/27 (3.7%) 1
    Insomnia 2/14 (14.3%) 2 0/6 (0%) 0 4/51 (7.8%) 4 13/49 (26.5%) 13 3/27 (11.1%) 3
    Depression 1/14 (7.1%) 1 0/6 (0%) 0 4/51 (7.8%) 4 5/49 (10.2%) 5 0/27 (0%) 0
    Libido decreased 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Renal and urinary disorders
    Dysuria 2/14 (14.3%) 2 0/6 (0%) 0 5/51 (9.8%) 5 3/49 (6.1%) 3 2/27 (7.4%) 2
    Hematuria 2/14 (14.3%) 2 0/6 (0%) 0 1/51 (2%) 1 3/49 (6.1%) 3 0/27 (0%) 0
    Hydronephrosis 1/14 (7.1%) 1 0/6 (0%) 0 1/51 (2%) 1 1/49 (2%) 1 0/27 (0%) 0
    Micturition urgency 1/14 (7.1%) 1 0/6 (0%) 0 1/51 (2%) 1 1/49 (2%) 1 0/27 (0%) 0
    Pollakiuria 0/14 (0%) 0 0/6 (0%) 0 2/51 (3.9%) 2 2/49 (4.1%) 2 2/27 (7.4%) 2
    Urinary incontinence 1/14 (7.1%) 1 0/6 (0%) 0 2/51 (3.9%) 2 1/49 (2%) 1 0/27 (0%) 0
    Urinary retention 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Reproductive system and breast disorders
    Perineal pain 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Vaginal discharge 1/14 (7.1%) 1 0/6 (0%) 0 1/51 (2%) 1 2/49 (4.1%) 2 0/27 (0%) 0
    Vaginal ulceration 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Vulvovaginal swelling 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Pelvic pain 0/14 (0%) 0 0/6 (0%) 0 5/51 (9.8%) 5 1/49 (2%) 1 1/27 (3.7%) 1
    Vaginal hemorrhage 0/14 (0%) 0 0/6 (0%) 0 2/51 (3.9%) 2 2/49 (4.1%) 2 3/27 (11.1%) 3
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 2/14 (14.3%) 2 1/6 (16.7%) 1 14/51 (27.5%) 14 15/49 (30.6%) 15 5/27 (18.5%) 5
    Cough 4/14 (28.6%) 4 2/6 (33.3%) 2 7/51 (13.7%) 7 8/49 (16.3%) 8 4/27 (14.8%) 4
    Atelectasis 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Dyspnea exertional 1/14 (7.1%) 1 1/6 (16.7%) 1 1/51 (2%) 1 2/49 (4.1%) 2 1/27 (3.7%) 1
    Hemoptysis 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Nasal congestion 1/14 (7.1%) 1 1/6 (16.7%) 1 3/51 (5.9%) 3 3/49 (6.1%) 3 0/27 (0%) 0
    Paranasal sinus hypersecretion 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Pleural effusion 0/14 (0%) 0 0/6 (0%) 0 3/51 (5.9%) 3 1/49 (2%) 1 1/27 (3.7%) 1
    Productive cough 1/14 (7.1%) 1 0/6 (0%) 0 1/51 (2%) 1 3/49 (6.1%) 3 0/27 (0%) 0
    Epistaxis 0/14 (0%) 0 0/6 (0%) 0 5/51 (9.8%) 5 1/49 (2%) 1 0/27 (0%) 0
    Oropharyngeal pain 0/14 (0%) 0 1/6 (16.7%) 1 2/51 (3.9%) 2 1/49 (2%) 1 1/27 (3.7%) 1
    Pulmonary edema 0/14 (0%) 0 1/6 (16.7%) 1 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Upper respiratory tract infection 2/14 (14.3%) 2 0/6 (0%) 0 2/51 (3.9%) 2 2/49 (4.1%) 2 1/27 (3.7%) 1
    Skin and subcutaneous tissue disorders
    Rash 2/14 (14.3%) 2 1/6 (16.7%) 1 7/51 (13.7%) 7 6/49 (12.2%) 6 0/27 (0%) 0
    Alopecia 1/14 (7.1%) 1 0/6 (0%) 0 6/51 (11.8%) 6 7/49 (14.3%) 7 2/27 (7.4%) 2
    Dermatitis contact 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Dry skin 1/14 (7.1%) 1 0/6 (0%) 0 2/51 (3.9%) 2 6/49 (12.2%) 6 2/27 (7.4%) 2
    Erythema 1/14 (7.1%) 1 0/6 (0%) 0 1/51 (2%) 1 2/49 (4.1%) 2 1/27 (3.7%) 1
    Hyperhidrosis 1/14 (7.1%) 1 0/6 (0%) 0 1/51 (2%) 1 1/49 (2%) 1 0/27 (0%) 0
    Night sweats 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 1/49 (2%) 1 0/27 (0%) 0
    Onycholysis 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 3/49 (6.1%) 3 0/27 (0%) 0
    Palmar-plantar erythrodysesthesia syndrome 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 3/49 (6.1%) 3 0/27 (0%) 0
    Pruritus 1/14 (7.1%) 1 3/6 (50%) 3 7/51 (13.7%) 7 0/49 (0%) 0 3/27 (11.1%) 3
    Rash erythematous 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Rash maculo-papular 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 3/49 (6.1%) 3 0/27 (0%) 0
    Skin lesion 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Swelling face 1/14 (7.1%) 1 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 0/27 (0%) 0
    Vascular disorders
    Hypertension 1/14 (7.1%) 1 0/6 (0%) 0 7/51 (13.7%) 7 6/49 (12.2%) 6 2/27 (7.4%) 2
    Embolism 0/14 (0%) 0 0/6 (0%) 0 0/51 (0%) 0 0/49 (0%) 0 2/27 (7.4%) 2
    Flushing 1/14 (7.1%) 1 1/6 (16.7%) 1 1/51 (2%) 1 3/49 (6.1%) 3 0/27 (0%) 0
    Hematoma 0/14 (0%) 0 0/6 (0%) 0 3/51 (5.9%) 3 0/49 (0%) 0 0/27 (0%) 0
    Hypotension 0/14 (0%) 0 0/6 (0%) 0 1/51 (2%) 1 3/49 (6.1%) 3 3/27 (11.1%) 3
    Lymphedema 1/14 (7.1%) 1 1/6 (16.7%) 1 0/51 (0%) 0 2/49 (4.1%) 2 0/27 (0%) 0
    Deep vein thrombosis 0/14 (0%) 0 1/6 (16.7%) 1 1/51 (2%) 1 1/49 (2%) 1 0/27 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Harold Keer
    Organization Astex Pharmaceuticals, Inc.
    Phone 925-719-0741
    Email Harold.Keer@astx.com
    Responsible Party:
    Astex Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT01696032
    Other Study ID Numbers:
    • SGI-110-02
    First Posted:
    Sep 28, 2012
    Last Update Posted:
    May 25, 2021
    Last Verified:
    Apr 1, 2021