CRP on Radiobiological and Clinical Studies on Viral-Induced Cancer's Response to Radiotherapy
Study Details
Study Description
Brief Summary
The purpose of this trial is to study clinical effects of two/four high dose rate (HDR) brachytherapy applications and teletherapy with or without weekly cisplatin in cervix cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This study uses 2x2 design to test external beam radiotherapy (46 Gy in 23 daily fractions) with and without HDR brachytherapy (2 fractions of 9 Gy versus 4 fractions of 7 Gy) with and without weekly Cisplatin (40 mg/sqm) The overall objective was to test the clinical outcome and toxicity of a resource-sparing schedule of radiotherapy with or without chemotherapy treatment for cervix cancer, to detect molecular markers that will predict tumor control/resistance and to establish whether E6 and E7 viral proteins predict cellular radiosensitivity in oxic and hypoxic conditions in vitro and tumor control/resistance in vivo. A new component of the CRP was added, for which the objective is to optimize the data capture, provide more details of normal tissue outcomes following cancer treatments in developing countries and validate this approach using patients participating in the ongoing CRP. This will be achieved by exploring data capture using the questionnaire template on a computer in face-to-face interviews ("active" data collection) and comparing it with standard data collection obtained from the clinical notes ("passive" data collection) during the still ongoing CRP E3.30.24. The method of data collection will be chosen at random for each case stratified by centre. The reason for using an ongoing CRP is that it will test the usefulness of the new method and validate it in a multicentre study. During the performance of the new CRP, the same institutions as for E3.30.24 will be engaged.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: EBR plus 2 HDBT fractions External Beam Radiotherapy High Dose Brachytherapy (2 fractions of 9Gy) |
Radiation: Radiotherapy
External Beam Radiation 46Gy in 23 daily fractions
High Dose Brachytherapy 2 fractions of 9Gy
|
| Active Comparator: EBR plus 4 fractions HDBT External Beam Radiotherapy High Dose Brachytherapy (4 fractions of 7Gy) |
Radiation: Radiotherapy
External Beam Radiotherapy 46Gy in 23 daily fractions
High Dose Brachytherapy 4 fractions of 7Gy
|
| Experimental: EBR/2 HDBT fractions/Chemotherapy External Beam Radiation High Dose Brachytherapy (2 fractions of 9Gy) Cisplatin |
Radiation: Radiotherapy/Cisplatin
External Beam Radiation 46Gy in 23 daily fractions
High Dose Brachytherapy 2 fractions of 9Gy
Cisplatin 40 mg/sqm weekly
|
| Experimental: EBR/4 fractions HDBT/chemotherapy External Beam Radiation High Dose Brachytherapy (4 fractions of 7Gy) Cisplatin |
Radiation: Radiotherapy/Cisplatin
External Beam Radiotherapy 46Gy in 23 daily fractions
High Dose Brachytherapy 4 fractions of 7Gy
Cisplatin 40mg/sqm weekly
|
Outcome Measures
Primary Outcome Measures
- Clinical Outcome [5 years]
- Treatment Toxicity [3 months]
- Molecular markers that will predict tumor control/resistance [5 years]
- Whether E6 and E7 viral proteins predict cellular radiosensitivity in oxic and hypoxic conditions in vitro and tumor control/resistance in vivo [5 years]
- Effectiveness of a questionnaire template on a computer in face-to-face interviews in a multicentre multinational study. [2 years]
Eligibility Criteria
Criteria
INCLUSION CRITERIA:
-
Histologically confirmed cervix cancer.
-
FIGO stage IIB and IIIB
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Age over 18 years
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Karnofsky status >/= 50
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No significant medical contraindications to the administration of full dose chemotherapy.
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Adequate bone marrow function -- Haemoglobin ³ 10 g/dl without or with transfusion, white blood count ³ 4000/mL, platelet count ³ 140,000/mL.
-
Adequate renal function: creatinine < 1.2 mg/dL or 120 μmol/l (urinary diversion is permitted). Electrolytes and calcium within normal limits for institution. Liver function tests if clinically indicated. Tests have to be obtained within 30 days before registration.
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Expected good compliance for follow-up.
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Written informed consent for participation in this study.
EXCLUSION CRITERIA:
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Recent malignancy, other than the index cervical carcinoma or non-melanoma cutaneous cancers, diagnosed within 5 years of entry
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Life expectancy <6 months, for any reason other than the index cervical carcinoma
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Any severe medical ailment, continuing pregnancy, or breast feeding, as conditions that interfere in present treatment
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Previous chemotherapy in past 1 year
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Severe psychiatric disorder, making compliance and follow-up difficult.
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Paraaortic nodes (PAN >1 cm), suspicious or positive for metastatic involvement on radiological imaging. (Note: patients with positive pelvic lymph nodes are still eligible for the study, but they cannot have suspicious or positive PAN.)
-
Bilateral hydronephrosis
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Prior radiation to the pelvis
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Vienna; Department of Radiotherapy and Radiobiology | Vienna | Austria | ||
| 2 | rmandade de Santa Casa de Misericordia de Porto Alegre; Hospital Santa Rita | Porto Alegre | Brazil | ||
| 3 | Peel Regional Cancer Centre | Mississauga | Ontario | Canada | |
| 4 | Department of Atomic Energy (DAE); Tata Memorial Centre (TMC); Tata | Mumbai | India | ||
| 5 | National Cancer Center | Seoul | Korea, Republic of | ||
| 6 | Radiotherapy and Oncology University Clinic | Skopje | Macedonia, The Former Yugoslav Republic of | ||
| 7 | Institut National d'Oncologie | Rabat | Morocco | ||
| 8 | Bahawalpur Institute of Nuclear Medicine and Oncology (BINO) | Bahawalpur | Pakistan | ||
| 9 | Instituto Nacional de Enfermedades Neoplásicas | Lima | Peru | ||
| 10 | Department of Radiation Oncology, Groote Schuur Hospital | Cape Town | South Africa | ||
| 11 | Christie Hospital; NHS Trust | Manchester | United Kingdom |
Sponsors and Collaborators
- International Atomic Energy Agency
Investigators
- Study Director: Eduardo H. Zubizarreta, M.D., International Atomic Energy Agency (IAEA)
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Green JA, Kirwan JM, Tierney JF, Symonds P, Fresco L, Collingwood M, Williams CJ. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet. 2001 Sep 8;358(9284):781-6.
- Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1137-43.
- Nag S, Chao C, Erickson B, Fowler J, Gupta N, Martinez A, Thomadsen B; American Brachytherapy Society. The American Brachytherapy Society recommendations for low-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys. 2002 Jan 1;52(1):33-48. Erratum in: Int J Radiat Oncol Biol Phys 2002 Mar 15;52(4):1157.
- Nag S, Erickson B, Thomadsen B, Orton C, Demanes JD, Petereit D. The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys. 2000 Aug 1;48(1):201-11.
- Pearcey R, Brundage M, Drouin P, Jeffrey J, Johnston D, Lukka H, MacLean G, Souhami L, Stuart G, Tu D. Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol. 2002 Feb 15;20(4):966-72.
- Petereit DG, Pearcey R. Literature analysis of high dose rate brachytherapy fractionation schedules in the treatment of cervical cancer: is there an optimal fractionation schedule? Int J Radiat Oncol Biol Phys. 1999 Jan 15;43(2):359-66. Review.
- Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999 May;17(5):1339-48.
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