Second-Line Therapy Study For Potentially Platinum-Sensitive Relapsed Ovarian Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00316173
First received: April 19, 2006
Last updated: November 21, 2012
Last verified: November 2012
  Purpose

This study was designed to find the most effective and safest doses of both HYCAMTIN and CARBOPLATIN that can be given for the treatment of ovarian cancer. This study may allow researchers to determine the effectiveness of combining HYCAMTIN and CARBOPLATIN.


Condition Intervention Phase
Ovarian Cancer
Neoplasms, Ovarian
Drug: topotecan
Drug: CARBOPLATIN
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Single-Arm, Phase II Study of IV Weekly (Days 1 and 8 Every 21 Days) HYCAMTIN in Combination With Carboplatin (Day 1 Every 21 Days) as Second-Line Therapy in Subjects With Potentially Platinum-Sensitive Relapsed Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With the Indicated Response [ Time Frame: From start of treatment to evidence of CR or PR (up to 39.3 weeks). ] [ Designated as safety issue: No ]
    Overall response rate, as determined by radiologic evaluation (utilizing the World Health Organization [WHO] criteria and/or physical examination was measured. Complete response (CR: complete disappearance of all lesions), partial response (PR: >50% decrease in the measurements of the largest lesions with no appearance of new lesions), stable disease (SD: no change in tumor size for at least 8 weeks) and progressive disease (PD: >25% increase in measurements of lesions or appearance of new lesions).


Secondary Outcome Measures:
  • Time to Response [ Time Frame: From start of treatment to evidence of PR or CR (up to 39.3 weeks) ] [ Designated as safety issue: No ]
    Time to response was calculated as the time from start of treatment until first evidence of partial response (PR; >50% decrease in the measurements of the largest lesions with no appearance of new lesions) or complete response (CR; complete disappearance of all lesions).

  • Duration of Response [ Time Frame: From time of PR or CR to disease progression/death (up to 56.0 weeks) ] [ Designated as safety issue: No ]
    Duration of response was calculated as the time from first documented PR or CR until disease progression or death. For participants who did not have disease progression or did not die, the date on which alternative anti-cancer therapy began was used, or the date of last contact (if sooner). The word used for such participants was "censored".

  • Progression-free Survival [ Time Frame: From start of treatment to disease progression/death (up to 67.7 weeks) ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) was calculated as the time from the start of treatment until disease progression or death. For participants who did not have disease progression or did not die, the date on which alternative anti-cancer therapy began was used, or the date of last contact (if sooner). The word used for such participants was "censored". Although "Time to Disease Progression" was stated as an endpoint in the protocol, the definition given in the protocol (and used in the study) was that of "PFS". As such, "PFS" was measured, not "Time to Disease Progression".

  • Number of Participants Who Died From the Start of Treatment to Follow-up [ Time Frame: From start of treatment to death (up to 110.4 weeks). ] [ Designated as safety issue: No ]
    The number of participants who died from the start of treatment to follow-up was calculated. For participants who did not die, the date of last contact was used. The word used for such participants was "censored".

  • The Number of Participants Classified as Responders in Cancer Antigen 125 (CA-125) [ Time Frame: Baseline to end of study (up to 54.7 weeks). ] [ Designated as safety issue: No ]
    CA-125 is a "tumor marker", found in greater concentration in tumor cells than other cells of the body. Participants were classed as responders if their CA-125 level at the end of study was 50% or less of baseline. In addition, a confirmatory sample (taken at least 28 days after the first sample) must have also been 50% or less of baseline.

  • Time to Disease Progression [ Time Frame: From start of treatment to disease progression/death ] [ Designated as safety issue: No ]
    Although "Time to Disease Progression" was stated as an endpoint in the protocol, the definition given in the protocol (and used in the study) was that of "Progression-free Survival". As such, "Progression-free Survival" was measured, not "Time to Disease Progression". See the outcome measure entitled "Progression-free Survival" for data pertaining to time to disease progression.


Enrollment: 77
Study Start Date: March 2005
Study Completion Date: March 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single-arm
HYCAMTIN at a dose of 2.0 - 2.5mg/m2 on Days 1 and 8 every 21 days followed by carboplatin at AUC 5 on Day 1, every 21 days
Drug: topotecan
HYCAMTIN at a dose of 2.0 mg/m2 on Days 1 and 8 every 21 days followed by carboplatin at AUC 5 on Day 1
Drug: CARBOPLATIN
HYCAMTIN at a dose of 2.0 mg/m2 on Days 1 and 8 every 21 days followed by carboplatin at AUC 5 on Day 1

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Subject must have baseline laboratory values as follows:
  • Hemoglobin 9.0 g/dL
  • Neutrophils 1,500/mm3
  • Platelets 100,000/mm3
  • Creatinine 1.5 mg/dL ( 133 mol/l) or creatinine clearance 60 mL/min
  • Serum bilirubin < 2.0 mg/dL (< 35 umol/L)
  • SGOT/AST, SGPT/ALT and alkaline phosphatase < 2 times ULN if liver metastases are absent by abdominal CT or MRI or < 5 times ULN if liver metastases are present
  • Subject is allowed to have received, but is not required to have received, one additional prior non-cytotoxic regimen for management of recurrent or persistent disease according to the following definition: Non-cytotoxic (biologic or cytostatic) agents include (but are not limited to) monoclonal antibodies, cytokines, and small-molecule inhibitors of signal transduction
  • Subject is female 18 years of age with an ECOG Performance Status of 0, 1 or 2
  • Subject has recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer which was histologically confirmed at the time of the primary diagnosis
  • Subject has received one prior platinum-based chemotherapeutic regimen (containing either carboplatin or cisplatin) for the treatment of primary disease. Consolidation chemotherapy is not permitted
  • Subject's disease is considered potentially platinum-sensitive (i.e., have had a platinum-free interval following complete response to carboplatin or cisplatin of greater than 6 months)
  • Subject must have at least one measurable lesion as determined by diagnostic studies including CT or MRI or physical exam. Measurable disease must be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be 20 mm in their longest dimension when measured by conventional techniques, including palpation, plain X-ray, CT and MRI, or 10 mm when measured by spiral CT. Palpable tumor masses that cannot be evaluated radiologically must have 2 diameters 20 mm. An attempt to document lesion size by ultrasound should be undertaken for palpable lesions not visualized on CT (or MRI).
  • The same diagnostic imaging method used to evaluate disease must be used throughout the study to evaluate lesions consistently
  • Stable blood, liver and renal functions.
  • Subjects of child-bearing potential must be practicing adequate contraception (e.g. oral contraceptives, diaphragm plus spermicide, or IUD) for at least 3 months prior to study start. The same contraceptive method should be used throughout the study and continue for at least 4 weeks after the end of the study

Exclusion criteria:

  • Pregnant or lactating.
  • Subject has received more than 1 prior chemotherapy regimen or a history of consolidation cytotoxic chemotherapy
  • Subject has concomitant or history of previous malignancies, with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease-free for 5 years
  • Subject has brain metastases as documented by CT or MRI. Note: Asymptomatic subjects do not require CT or MRI to rule out brain metastases
  • Received previous treatment with HYCAMTIN.
  • Subject has received an investigational agent within 30 days or 5 half-lives (whichever is longer) prior to study entry
  • Received prior radiation therapy for ovarian cancer
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00316173

  Show 22 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Schwartz PE, Rose PG, Monk BJ, et al. An open-label, single arm, phase II study of IV weekly (days 1 and 8) topotecan in combination with carboplatin (day 1) every 21 days as second-line therapy in subjects with platinum sensitive relapsed ovarian cancer: First stage results. J Clin Oncol. 2008; 26 (May 20 suppl). Abstract 16518

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00316173     History of Changes
Other Study ID Numbers: 104864/902
Study First Received: April 19, 2006
Results First Received: October 20, 2009
Last Updated: November 21, 2012
Health Authority: Canada: Canadian Institutes of Health Research
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
HYCAMTIN
ovarian cancer
recurrent
relapsed
carboplatin
topotecan
potentially platinum-sensitive

Additional relevant MeSH terms:
Neoplasms
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carboplatin
Topotecan
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014