There is still no level I-II evidence for cytoreductive surgery in recurrent ovarian cancer. This is also the conclusion of a Cochrane Review of Galaal et al. published in June 2010. The most active chemotherapy in platinum sensitive recurrent…
ID
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
- Obstetric and gynaecological therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Comparing progression free survival (defined as the interval between date of
randomization and progressive disease or death of any cause) in the two
study-arms
Secondary outcome
Comparing overall survival (defined as the interval between date of
randomization and date of death), quality of life, morbidity, mortality,
toxicity and tumour response following treatment in the two arms.
With respect to secondary cytoreductive surgery : determining the effect of
complete and incomplete surgery on progression free survival and overall
survival, identifying predictive factors and criteria for patient selection for
complete surgery.
Background summary
Each year approximately 1100 women are diagnosed with ovarian cancer and around
900 will die of the disease. This high mortality rate is due to the fact that
at least 60% of the patients presents with an advanced stage disease. In the
Netherlands, the population-based 5-year survival rate of these patients is
only 20-25%. Standard front-line therapy for advanced stage ovarian carcinoma
is primary cytoreductive surgery followed by intravenous platinum and
taxane-based chemotherapy. Patients with first recurrence of ovarian cancer are
treated with palliative chemotherapy according to the national guideline. The
median overall survival reported in large prospective chemotherapy only trials
is 18 and 29 months. The progression free survival in the superior arms in
these chemotherapy only trials is 8, 6 and 13 months. Where the role of
cytoreductive surgery is widely accepted in the initial treatment of ovarian
cancer, its value in recurrent ovarian cancer has not yet been established.
Many studies, nearly all retrospective and with selected patient cohorts have
demonstrated a clear survival benefit for patients undergoing secondary
cytoreductive surgery. In 2008, Bristow et al. conducted a meta-analysis on
2019 patients with secondary cytoreductive surgery for recurrent ovarian
cancer. Median overall survival ranged from 10-62 months. Progression free
survival was not reported.
Study objective
There is still no level I-II evidence for cytoreductive surgery in recurrent
ovarian cancer. This is also the conclusion of a Cochrane Review of Galaal et
al. published in June 2010. The most active chemotherapy in platinum sensitive
recurrent ovarian cancer provided only a limited activity with a median overall
survival of 29 months. Improvement is clearly needed for these patients.
Survival rates up to 62 months in patients with complete tumor resection are
reported in series with selected patient cohorts. Therefore a randomized
controlled trial comparing surgery and chemotherapy versus chemotherapy alone
is needed.
Study design
Multicenter, randomized controlled Phase III trial
Intervention
Control arm: intravenous platinum containing chemotherapy
Experimental arm: secondary cytoreductive surgery followed by intravenous
platinum containing chemotherapy
Study burden and risks
Studies suggest that secondary cytoreductive surgery can be accomplished with a
similar morbidity and mortality rate as primary debukling for advanced ovarian
cancer. Significant per-operative morbidity is estimated 19,2% and consist of
postoperative hemorrhage, intra operative bowel injury and intra-abdominal
infection. The peri-operative mortality rate is estimated 1,2%. We expect that
a maximum of 5% of patients in the experimental group will start chemotherapy
more than six weeks after secondary cytoredutive surgery because of surgery
related morbidity.
Geert Grooteplein-Zuid 10
6525 GA Nijmegen
NL
Geert Grooteplein-Zuid 10
6525 GA Nijmegen
NL
Listed location countries
Age
Inclusion criteria
• Age >= 18 years
• First recurrence of histologically or cytologically proven epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer of FIGO stage Ic-IV (FIGO system 1988)
• First-line treatment consisted of complete or optimal (<= 1 cm) cytoreductive
surgery and a minimum of six courses (neo-adjuvant) platinum-taxol based chemotherapy
• A clinically disease-free interval of at least 6 months after end of first-line
treatment, the latter defined as the day the last chemotherapy was administered
• First recurrence defined as clinical and radiological signs (CT-scan) of
recurrence or elevated CA 125 (GCIG criteria) and radiological signs (CT-scan)
• If there is any doubt whether or not an abnormal finding on CT-scan is
recurrent ovarian cancer, confirmation of recurrence with cytological or histological
investigation is warranted
• Good performance status (ECOG 0-1)
• Ascites < 500 ml (pocket < 8 cm on ultrasound examination)
• Complete resection seems possible (estimated by a gynecologic oncologist)
• Adequate hematological, renal, and hepatic function to permit platinum
based chemotherapy: WBC > 3.0 x 10*/L, platelets > 100 x 10*/L, serum
creatinine < 1.25 x upper normal range (40-90 µmol/L), serum bilirubin < 1.25 x upper normal
range (< 17 µmol/L)
• Informed consent must be obtained and documented according to national
and local regulatory requirements and the local rules followed in the institution before
randomization
• Quality of life baseline questionnaires should be filled in after informed
consent, preferably before randomization but at least before start treatment
Exclusion criteria
• Participation in interfering trial
• Non-epithelial or borderline ovarian tumours
• Other primary malignancy except for carcinoma in situ and basal or
squamous cell carcinoma of the skin
• Patients with platinum-refractory or resistant tumours
• Intra-abdominal metastatic disease that hampers complete cytoreduction
• Extra-abdominal metastatic disease that hampers complete cytoreduction
• Palliative surgery already planned (e.g. bowel surgery)
• Patients with secondary, third and later recurrence
• Any disease, medical history or medication not allowing surgery and/or
platinum based chemotherapy
• Prior therapy with respect to recurrence
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL36413.091.11 |
| OMON | NL-OMON20627 |