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

This study has been terminated.
(The study was "withdrawn" due to certain adverse events [hypersensitivity].)
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00748527
First received: September 5, 2008
Last updated: July 9, 2013
Last verified: September 2008
  Purpose

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.


Condition Intervention Phase
Fallopian Tube Cancer
Ovarian Cancer
Peritoneal Cavity Cancer
Drug: carboplatin
Drug: decitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Cancer Research UK Randomised, Multicentre, Phase II Trial of the DNAhypomethylating Agent, 5-Aza-2'-Deoxycytidine (Decitabine) Given Intravenously in Combination With Carboplatin, Versus Carboplatin Alone Given 4 Weekly in Patients With Progressive, Advanced Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate (PR or CR) in all patients (regardless of methylation status) as measured by RECIST criteria or CA-125 criteria [ Designated as safety issue: No ]
  • Progression-free survival and overall survival [ Designated as safety issue: No ]
  • Adverse events as measured by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Total dose and dose intensity of carboplatin and decitabine [ Designated as safety issue: No ]
  • Incidence of grade 3-4 hypersensitivity reactions [ Designated as safety issue: Yes ]
  • Correlation between peak plasma levels of decitabine and global and CpG island specific DNA methylation in peripheral blood mononuclear cells [ Designated as safety issue: No ]
  • Correlation between response (PR or CR) and global and CpG island specific DNA methylation in peripheral blood mononuclear cells [ Designated as safety issue: No ]
  • Correlation between response (PR or CR) and CpG island specific DNA methylation in plasma DNA [ Designated as safety issue: No ]
  • CpG island specific DNA methylation in plasma and tumor DNA [ Designated as safety issue: No ]
  • CpG island specific DNA methylation in tumor DNA and expression of genes as measured by RNA or protein assays [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]
  • Immunoassays of proteins in plasma [ Designated as safety issue: No ]
  • CpG island specific DNA methylation in tumor DNA [ Designated as safety issue: No ]

Estimated Enrollment: 134
Study Start Date: July 2007
Study Completion Date: November 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I
Patients receive carboplatin IV over 30-60 minutes on day 1.
Drug: carboplatin
Given IV
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
Given IV
Drug: decitabine
Given IV

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00748527

Locations
United Kingdom
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Leicester Royal Infirmary
Leicester, England, United Kingdom, LE1 5WW
Royal Marsden - London
London, England, United Kingdom, SW3 6JJ
Hammersmith Hospital
London, England, United Kingdom, W12 OHS
Saint Bartholomew's Hospital
London, England, United Kingdom, EC1A 7BE
Mount Vernon Cancer Centre at Mount Vernon Hospital
Northwood, England, United Kingdom, HA6 2RN
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT
Weston General Hospital
Weston-super-Mare, England, United Kingdom, BS23 4TQ
Belfast City Hospital Trust Incorporating Belvoir Park Hospital
Belfast, Northern Ireland, United Kingdom, BT8 8JR
Edinburgh Cancer Centre at Western General Hospital
Edinburgh, Scotland, United Kingdom, EH4 2XU
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, United Kingdom, G12 0YN
Sponsors and Collaborators
Cancer Research UK
Investigators
Study Chair: Stanley B. Kaye, MD, FRCP Royal Marsden NHS Foundation Trust
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00748527     History of Changes
Obsolete Identifiers: NCT00514124
Other Study ID Numbers: CRUK-PH2/051, CDR0000613805, EUDRACT-2006-002324-41, MGI-CRUK-PH2/051, CTA-21106/0219/001
Study First Received: September 5, 2008
Last Updated: July 9, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
fallopian tube cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian epithelial cancer
peritoneal cavity cancer

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Ovarian Diseases
Peritoneal Diseases
Urogenital Neoplasms
Carboplatin
Decitabine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014