LOROCSON study: Late Onset Recurrent Ovarian Cancer: Surgery Or Not.

A randomized phase III study for the treatment of recurrent epithelial ovarian cancer: chemotherapy alone versus chemotherapy followed by secondary cytoreductive surgery in patients with a disease-free interval of more than 6 months: LOROCSON Late Onset Recurrent Ovarian Cancer: Surgery Or Not
Objectives:
The general purpose of the study is to evaluate the benefits and risks of secondary cytoreductive surgery in patients with late onset recurrent epithelial ovarian cancer. The study will be prospective, multi-center, Study endpoints are primary: progression-free survival and secondary: survival, toxicity, surgical treatment related complications and quality of life.
Patient selection criteria:
* Inclusion: recurrence of epithelial ovarian cancer, after first line chemotherapy with a disease-free interval of at least 6 months, age> 18 years, WHO Performance status 0-2. The first-line therapy should have consisted of at least 4 courses of either cisplatin or carboplatin.
* Exclusion: more than one line chemotherapy, complete bowel obstruction, metastasized carcinoma (other tumor), leptomeningeal or brain metastases.
Randomization:
* Stage at initial diagnosis (early I-IIa vs. advanced stage IIb-IV).
* Length of disease free interval between the time of curation and registration to this protocol (between 6 months and 2 years versus more than 2 years).
* Response to 2nd line induction chemotherapy, i.e. first three cycles of this trial (no change versus partial remission versus complete remission).
* Number of measurable tumor lesions at registration (1 versus more than 1).
* Largest tumor size of recurrence at registration (< 5 cm vs. > 5cm).
* Institution.
* Peritonitis or ascites present at initial surgery.
* Tumor-diameter after initial surgery (no, 0-1 cm, >1 cm).
Trial design:
After registration the patient will immediately start the first course of chemotherapy. After the induction chemotherapy the response to therapy will be evaluated. In case of progressive disease the patient will go off treatment. The other patients will be randomized to either continuation of the chemotherapy without surgery (treatment A) versus secondary cytoreductive surgery followed by chemotherapy (treatment B).
Clinical evaluation, laboratory tests and follow up:
During the course of the study the following examinations will be done: history and general physical examination, gynecological examination and ultrasound, WHO performance status, laboratory analysis ( serum CA 125, Hb, Ht and albumine) abdominal-pelvic computed tomography (CAT scan) and the QLQ OV 28.
Patient registration
The following items will be registered: institution and responsible physician, initials of the patient, birthday and hospital record number, date of last chemotherapy cycle (and type of chemotherapy), date of diagnosis of recurrence, stage of disease at initial diagnosis (FIGO), number of measurable lesions and largest diameter, WHO performance status, peritonitis or ascites present at initial surgery and tumor-diameter after initial surgery (no, 0-1 cm, >1 cm)
Statistical considerations
With a power analysis we calculated that 522 patients must be randomized in a period of 5 years. Assuming that 75% of the patients will reach the randomization procedure 700 patients should be registered. This means that 140 patients should be registered each year.

The median progression-free survival in the chemotherapy- alone arm is assumed to be 13 months. It is assumed that the addition of surgery increases the median progression-free survival with four months.

After registration the patient will immediately start the first course of chemotherapy. After the induction chemotherapy the response to therapy will be evaluated. In case of progressive disease the patient will go off treatment. The other patients will be randomized to either continuation of the chemotherapy without surgery (treatment A) versus secondary cytoreductive surgery followed by chemotherapy (treatment B).