1.
PO2868: Phase IV-II trial of Temozolomide in a continuous oral administration scheme in the treatment of gynaecological sarcomas.
2. GEICO-0101: Phase III clinical trial to evaluate the treatment with the combination cisplatin plus topotecan followed by paclitaxel plus carboplatin compared to paclitaxel plus carboplatin as a first line treatment in women who have recently been diagnosed with advanced ovarian epithelial cancer.
1.
Title: Phase IV-II trial of Temozolomide in a continuous oral administration scheme in the treatment of gynaecological sarcomas.
PROTOCOL CODE: PO2868
OBJECTIVES:
- To evaluate the therapeutic activity, measured as the percentage of objective responses to Temozolomide orally administered in a continuous way, in patients with gynaecological sarcomas who have not been previously treated with chemotherapy
- Time to disease progression
- Duration of response
- Toxicity of Temozolomide
INCLUSION CRITERIA:
Patients should fulfil all the following criteria in order to be considered suitable for entry:
• Histological diagnosis of gynaecological sarcoma, including uterine as well as gynaecological sarcomas of other localizations: vagina, vulva, ovary and tube. The following types are susceptible to be included : leiomyosarcoma, malignant mixed mullerian tumors (homologous and heterologous) or carcinosarcoma, endometrial stromal sarcoma and gynaecological sarcomas of a non-specified nature.
• Locally advanced unresectable and /or metastatic disease.
• Patients should have at least an appraisable lesion according to the RECIST criteria, with evidence of progression in the last 8 weeks.
• Patients should not have received previous chemotherapeutic treatment.
• Age > 16 years old
• Functional state 0-2 (OMS)
• Appropriate medullary function, defined by: Neutrophils > 1500/mm3, Hb > 9g/dl, and platelets > 100.000/mm3.
• Biological parameters of creatinine clearance = / > 40 ml/min, bilirubin serum < 1.5 times the upper limit of normal and AST or ALT < 2.5 times the upper limit of normal.
• Women of fertile age should be using an appropriate birth-control method (prescribed under medical supervision). Patient's informed consent in writing.
TOTAL NUMBER OF PATIENTS:
The projected total number of assessable patients to be included is 25. An intermediate analysis will be carried out after the inclusion of the first 16 patients, and the inclusion will only continue until the end if a minimum of 2 responses is obtained in these patients.
STRATIFICATION:
Patients will receive Temozolomide orally without ingesting food from one hour before until one hour after the dose, although they will be allowed to take a glass of water with the capsules. The calculated dose will be administered, in a continuous way for 6 weeks, in the morning.
The doses may be rounded off up to 5mg to adopt them to the dose available in capsules. The cycles of 6 weeks will be repeated after an interval of 3 weeks rest, providing there is haematological recovery. In case this has not taken place (Neutrophils > 1500/mm3 and/or platelets > 100.000/mm3), it is necessary to wait the necessary time until these levels are reached in order to begin the following cycle.
It will be indicated to the patients that they have to swallow the capsules whole and in quick succession, without chewing them. If vomiting takes place during the treatment, the administration of the dose will not be allowed to be repeated before the patient’s next projected dose.
The treatment will be prolonged for six and a half months (3 cycles) in patients for whom a response or stabilization of the disease was obtained and who have not experienced unacceptable toxicity.
2. Title: Phase III clinical trial to evaluate the treatment with the combination cisplatin plus topotecan followed by paclitaxel plus carboplatin compared to paclitaxel plus carboplatin as a first line treatment in women who have recently been diagnosed with advanced ovarian epithelial cancer.
PROTOCOL CODE: CAN-NCIC-OV16, NCT00028743, EORTC-55012, GEICO-0101
OBJECTIVES:
- Compare the efficacy of the treatment with cisplatin plus topotecan followed by paclitaxel plus carboplatin compared to the standard treatment with paclitaxel plus carboplatin as a first line chemotherapeutic treatment for patients recently diagnosed with stage IIB-IV ovarian epithelial cancer, or Fallopian tube cancer.
- Compare the overall survival of patients treated with these regimens.
- Compare the clinical objective response rates in patients with measurable disease at baseline.
- Compare the toxic effects of these regimens.
- Compare the CA 125 normalization rate in patients treated with these regimens.
- Compare the quality of life of patients treated with these regimens.
INCLUSION CRITERIA:
Patients should have documented evidence of advanced ovarian epithelial carcinoma or peritoneal cancer or cancer of the Fallopian tubes, and should not have received chemotherapy previously.
•
Histologically confirmed stage IIB-IV ovarian epithelial carcinoma. Patients with primary peritoneal tumours or tumours of the Fallopian tubes with equivalent histology may also participate in the study.
o Tumores de ovario No borderline
o Residual disease allowed
• If an open or incisional biopsy is not available, is allowed a fine-needle aspiration biopsy (FNAB) that demonstrates the presence of adenocarcinoma in the following circumstances:
o Presence of pelvic mass,
And
Omental cake or other metastasis larger than 2 cm in the upper abdomen, unless a stage IV disease has been detected,
And
Serum ratio CA125/CEA> 25. If the serum ratio CA125/CEA is < 25, a barium enema (or colonoscopy) and a gastroscopy (or a radiological exploration of the stomach) should be carried out for obtaining negative results discarding the presence of a primary tumor of these sites (< 6 weeks before randomization),
And
Normal mammogram (< 6 weeks)
•
All the planned pre-chemotherapy surgical interventions should be carried out ? 6 weeks before the randomization. Patients on whom it is planned to carry out reductive surgery MAY participate in the study.
• Illness in stage IIB to IV (the existence of residual disease is not necessary)
• Absence of previous radiotherapy or chemotherapy
• Functional state ECOG 0 or 1 at the moment of randomization.
• Age >= 18 and =< 75. Life expectancy equal to or greater than 12 weeks.
• Laboratory requirements: (the tests should be carried out in the 7 days prior to the randomization).
-
Granulocytes >= 2 x 10^9/L
- Platelets >= 150 x 10^9/L
- Creatinine serum =< ULN (upper limit of normal)
•
Radiological requirements: should be carried out in the 21 days prior to the randomization.
• Thorax x-ray
• CT scan, MRI, or abdominal / pelvic ecograph (should be post-operative if reductive surgery has been carried out; it can be pre-operative if only a biopsy of 1 cm or a cytology by FNAB has been obtained).
Exception:
it is not necessary to have a post-operative tomography if reductive surgery up to < 1cm has been carried out in the same centre where the randomization is carried out.
•
Other x-rays or tomographys that are clinically indicated.
• The patient's informed consent should be obtained according to the requirements of the IRB and the existing legislation.
• Patients should be available to complete the treatment and the follow up. The investigators should make sure that the patients randomized in this trial will allow complete collection of data regarding the treatment, toxicity and follow up.
• In accordance with the norms of the NCIC CTG, the treatment of the protocol should begin in the 10 days following the patient's randomization.
• The rest of the necessary basal evaluations should be completed.
TOTAL NUMBER OF PATIENTS:
A total of 800 patients (400 for each arm) will be recruited in the study for a 2-year period.
STRATIFICATION:
This is a randomized multi-centre study. Patients will be stratified according to: 1) centre, 2) age (=<65 years as opposed to > 65 years); 3) pre-randomization surgery (absence of reductive surgery as opposed to reductive surgery with residual macroscopic disease >= 1cm as opposed to reductive surgery with residual macroscopic disease < 1cm as opposed to reductive surgery without residual macroscopic disease). A procedure will be used to assign patients to one of the two treatment arms.
• Arm I: Patients receive cisplatin IV over 60 minutes on day 1 and topotecan IV over 30 minutes on days 1-5 of courses 1-4 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 of courses 5-8.
• Arm II: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 of courses 1-8.
Each patient will be treated with a total of 8 treatment cycles. The cycles will be administered every 21 days.
In both arms, the cycles should be separated by intervals of 21 days. The patients on whom it is planned to carry out reductive surgery should be subjected to this surgical intervention after cycles 3 or 4. In these cases, an interval of more than 21 days between cycles is allowed, but it is recommended that the time between intervention and chemotherapy does not exceed 3 weeks. The Questionnaires of Quality of Life should only be completed during the follow up visits after 3 and 6 months.
The patients will be evaluated every 3 months for 3 years, every 6 months for the 2 following years until the end of the fifth year and afterwards annually to document the relapse, progression, second line treatment and survival.