CClinicalTrials.gg
TerminatedNCT00748527Updated Jul 10, 2013

Carboplatin With or Without Decitabine in Treating Patients With Progressive, Advanced Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

A Phase 2 interventional study of carboplatin and decitabine in Fallopian Tube Cancer, Ovarian Cancer and Peritoneal Cavity Cancer, sponsored by Cancer Research UK. Terminated at 11 sites in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2013-07-10.

Sponsored by Cancer Research UK · Phase 2, Interventional, and Treatment

Why this study was terminated
The study was "withdrawn" due to certain adverse events \[hypersensitivity\].
Phase
Phase 2
Study type
Interventional
Enrollment
134
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

RATIONALE: Drugs used in chemotherapy, such as carboplatin and decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether carboplatin is more effective with or without decitabine in treating patients with ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.

PURPOSE: This randomized phase II trial is studying carboplatin and decitabine to see how well they work compared with carboplatin alone in treating patients with progressive, advanced ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.

Read the detailed description

OBJECTIVES:

Primary

  • To compare the response rate in patients with progressive, advanced ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer who have methylated hMLH1 DNA in plasma treated with carboplatin with vs without decitabine.

Secondary

  • To compare the response rate in all patients (regardless of methylation status) treated with these regimens.
  • To compare the progression-free survival and overall survival of patients treated with these regimens.
  • To compare the safety and tolerability of these regimens.
  • To determine the feasibility of combining decitabine with carboplatin.
  • To determine the incidence of hypersensitivity reactions to carboplatin.
  • To study the relationship between peak plasma levels of decitabine and global or CpG island specific methylation.
  • To study the relationship between global and gene specific methylation in peripheral blood mononuclear cells and response.

Tertiary

  • To correlate the methylation status of genes associated with drug resistance detected in plasma DNA with response.
  • To determine the sensitivity and specificity of methylation of genes associated with drug resistance detected in plasma DNA as a predictor of methylation status in tumor cells isolated from ascites or tumor biopsy.
  • To study methylation and expression of genes in tumor cells isolated from ascites or tumor biopsy before and after treatment with decitabine and/or carboplatin.
  • To investigate any correlation between methylation and expression of genes in surrogate tissues, body fluids, or tumor cells and response or progression-free survival.
  • To examine markers of cell death in plasma.
  • To compare the methylation in tumor taken at the time of presentation vs at the time of treatment.

OUTLINE: This is a multicenter study. Patients are stratified according to prior first-line treatment (platinum alone vs platinum and taxane vs platinum and other combination), WHO performance status (0 vs 1 vs 2), measurable disease criteria (RECIST criteria vs CA-125 criteria vs both), participating center, and the number of prior platinum-based regimens (1 vs 2). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive carboplatin IV over 30-60 minutes on day 1.
  • Arm II: Patients receive decitabine IV over 6 hours on day 1 and carboplatin IV over 30-60 minutes on day 8.

In both arms, treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection periodically for pharmacodynamic studies. Samples are assessed for methylation of hMLH1 by methylation-specific PCR; global DNA methylation by high performance liquid chromatography (HPLC) ; methylation of the MAGE-1A gene promoter by methylation-specific PCR or bisulfite pyrosequencing; and markers of apoptosis by ELISA. Pharmacokinetic studies of decitabine are also performed using blood samples from patients randomized to arm II. Ascitic fluid and/or tumor tissue samples may also be collected for pharmacodynamic studies.

After completion of study treatment, patients are followed at 28 days and then every 2 months thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

02

Conditions studied

  • Fallopian Tube Cancer
  • Ovarian Cancer
  • Peritoneal Cavity Cancer

Keywords

  • fallopian tube cancer
  • stage III ovarian epithelial cancer
  • stage IV ovarian epithelial cancer
  • recurrent ovarian epithelial cancer
  • peritoneal cavity cancer
03

In context

Ovarian Neoplasms

2,695 studies on the registry are indexed under Ovarian Neoplasms; 727 are open to participants now.

This study's planned enrollment of 134 is above the median of 60 across 2,030 interventional studies indexed under Ovarian Neoplasms.

Browse Ovarian Neoplasms studies →

Lead sponsor

Cancer Research UK is the lead sponsor of 83 studies on the registry; 12 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically proven ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer

    • Progressive disease as defined by RECIST criteria and/or CA-125 criteria
    • Advanced disease
  • Previously treated with 1-2 prior platinum-containing regimen(s)

    • Prior hormonal therapy does not count towards the prior treatment
    • Responded to the most recent prior platinum-containing regimen(s) OR no evidence of progression during platinum-containing therapy as documented by RECIST criteria or CA-125 criteria (for patients with no macroscopic residual disease after surgery who are not evaluable by CA-125)
  • Disease relapse 6-12 months after completion of the most recent platinum-containing therapy

    • Patients who received two prior lines of treatment must have had ≥ 6 months between their first and second lines of treatment
    • Patients with disease progression, as defined by CA-125 criteria alone, within 6 months after completion of their last treatment are eligible provided study treatment commences > 6 months after the last prior treatment
    • Patients with disease progression, as defined by GCIG guidelines, within 12 months after completion of their last treatment are eligible provided study treatment commences ≤ 14 months after the last prior treatment
  • Measurable disease by RECIST criteria and/or CA-125 criteria

    • Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques (physical examination, CT scan, x-ray, or MRI) or as ≥ 10 mm by spiral CT scan
    • Patients with evaluable disease by CA-125 criteria are eligible provided CA-125 is ≥ 2 times upper limit of normal (ULN) within 2 weeks prior to initiating study treatment
    • Disease is not considered measurable if patient received prior mouse antibodies or if there has been medical and/or surgical interference with the peritoneum or pleura (e.g., paracentesis) within the past 28 days
  • Ascites requiring therapeutic drainage allowed only if there is measurable disease by RECIST criteria

    • Ascites that do not require therapeutic drainage allowed even if disease is evaluable by CA-125 criteria alone

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • Hemoglobin ≥ 10.0 g/dL
  • WBC ≥ 3.0 x 10\^9/L
  • Neutrophil count ≥ 1.5 x 10\^9/L
  • Platelet count ≥ 100 x 10\^9/L
  • Bilirubin ≤ 30 μmol/L
  • ALT and/or AST ≤ 2.5 times ULN (≤ 5 times ULN if due to tumor involvement of liver)
  • EDTA/DTPA clearance ≥ 50 mL/min (uncorrected value)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception for 4 weeks prior to, during, and for 6 months after completion of study treatment
  • No known hepatitis B, hepatitis C, or HIV positivity
  • No non-malignant systemic disease, including active uncontrolled infection, that would make the patient a high medical risk
  • No other current malignancies, except adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin

    • Patients who have undergone potentially curative therapy for a prior malignancy are eligible provided there is no evidence of disease for ≥ 5 years and the patient is deemed to be at low risk for recurrence
  • No intolerance to carboplatin (with a dose of ≥ AUC 5), as defined by any of the following:

    • Neutropenia or thrombocytopenia causing dose delay of > 4 days on more than 2 occasions
    • Grade III or IV hypersensitivity reaction (not controlled by a desensitization regimen)
    • Hospitalization for confirmed febrile neutropenia (fever ≥ 38°C)
    • Requirement for platelet transfusion
  • No other condition that, in the investigator's opinion, would not make the patient a good candidate for this study

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy (alopecia, grade 1 neuropathy, and certain grade 1 toxicities allowed)
  • More than 28 days since prior maintenance therapy (e.g., erlotinib or bevacizumab)
  • More than 4 weeks since prior radiotherapy, endocrine therapy, immunotherapy, chemotherapy, biological therapy, or investigational agents
  • More than 4 weeks since prior major thoracic and/or abdominal surgery and recovered
  • No other concurrent anti-cancer therapy, including radiotherapy or investigational drugs
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Masking
None (open label)
Enrollment
134 participants (estimated)

Study arms

  • Active comparator
    Arm I

    Patients receive carboplatin IV over 30-60 minutes on day 1.

    Drug: carboplatin

  • Experimental
    Arm II

    Patients receive decitabine IV over 6 hours on day 1 and carboplatin IV over 30-60 minutes on day 8.

    Drug: carboplatin · Drug: decitabine

Interventions

  • Drugcarboplatin

    Given IV

  • Drugdecitabine

    Given IV

06

What researchers measure

Primary outcomes

  1. Response rate (partial response [PR] or complete response [CR]) in patients with methylated hMLH1 DNA in plasma as measured by RECIST criteria or CA-125 criteria

Secondary outcomes

  1. Response rate (PR or CR) in all patients (regardless of methylation status) as measured by RECIST criteria or CA-125 criteria

  2. Progression-free survival and overall survival

  3. Adverse events as measured by NCI CTCAE v3.0

  4. Total dose and dose intensity of carboplatin and decitabine

  5. Incidence of grade 3-4 hypersensitivity reactions

  6. Correlation between peak plasma levels of decitabine and global and CpG island specific DNA methylation in peripheral blood mononuclear cells

  7. Correlation between response (PR or CR) and global and CpG island specific DNA methylation in peripheral blood mononuclear cells

  8. Correlation between response (PR or CR) and CpG island specific DNA methylation in plasma DNA

  9. CpG island specific DNA methylation in plasma and tumor DNA

  10. CpG island specific DNA methylation in tumor DNA and expression of genes as measured by RNA or protein assays

  11. Correlation between response (PR, CR, or stable disease) and CpG island specific DNA methylation in tumor DNA and expression of genes by RNA or protein assays

  12. Immunoassays of proteins in plasma

  13. CpG island specific DNA methylation in tumor DNA

07

Study locations

11 sites
  • Leeds Cancer Centre at St. James's University Hospital
    Leeds, England LS9 7TF, United Kingdom
  • Leicester Royal Infirmary
    Leicester, England LE1 5WW, United Kingdom
  • Saint Bartholomew's Hospital
    London, England EC1A 7BE, United Kingdom
  • Royal Marsden - London
    London, England SW3 6JJ, United Kingdom
  • Hammersmith Hospital
    London, England W12 OHS, United Kingdom
  • Mount Vernon Cancer Centre at Mount Vernon Hospital
    Northwood, England HA6 2RN, United Kingdom
  • Royal Marsden - Surrey
    Sutton, England SM2 5PT, United Kingdom
  • Weston General Hospital
    Weston-super-Mare, England BS23 4TQ, United Kingdom
  • Belfast City Hospital Trust Incorporating Belvoir Park Hospital
    Belfast, Northern Ireland BT8 8JR, United Kingdom
  • Edinburgh Cancer Centre at Western General Hospital
    Edinburgh, Scotland EH4 2XU, United Kingdom
  • Beatson West of Scotland Cancer Centre
    Glasgow, Scotland G12 0YN, United Kingdom
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 10, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT00748527
Lead sponsor
Cancer Research UK
First posted
Sep 8, 2008
Start date
Jul 2007
Primary completion
Dec 2009
Completion
Nov 2010
Last update
Jul 10, 2013

Study contacts

Stanley B. Kaye, MD, FRCP
study chair · Royal Marsden NHS Foundation Trust
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Sep 2008. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion