Clinical trial NCT00122772: CRP on Radiobiological and Clinical Studies on Viral-Induced Cancer's Response to Radiotherapy
Official title: CRP on Radiobiological and Clinical Studies on Viral-induced Cancer's Response to Radiotherapy With Comprehensive Morbidity Assessment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cervix Cancer
Lead sponsor: International Atomic Energy Agency
Sponsor class: OTHER_GOV
First posted: 2005-07-22
Enrollment: 601
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: INCLUSION CRITERIA:

* Histologically confirmed cervix cancer.
* FIGO stage IIB and IIIB
* Age over 18 years
* Karnofsky status \>/= 50
* No significant medical contraindications to the administration of full dose chemotherapy.
* 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.
* Expected good compliance for follow-up.
* Written informed consent for participation in this study.

EXCLUSION CRITERIA:

* Recent malignancy, other than the index cervical carcinoma or non-melanoma cutaneous cancers, diagnosed within 5 years of entry
* Life expectancy \<6 months, for any reason other than the index cervical carcinoma
* Any severe medical ailment, continuing pregnancy, or breast feeding, as conditions that interfere in present treatment
* Previous chemotherapy in past 1 year
* Severe psychiatric disorder, making compliance and follow-up difficult.
* 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
* Prior radiation to the pelvis

Primary outcomes:
measure: Clinical Outcome
timeFrame: 5 years
measure: Treatment Toxicity
timeFrame: 3 months
measure: Molecular markers that will predict tumor control/resistance
timeFrame: 5 years
measure: Whether E6 and E7 viral proteins predict cellular radiosensitivity in oxic and hypoxic conditions in vitro and tumor control/resistance in vivo
timeFrame: 5 years
measure: Effectiveness of a questionnaire template on a computer in face-to-face interviews in a multicentre multinational study.
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: University of Vienna; Department of Radiotherapy and Radiobiology
city: Porto Alegre
country: Brazil
facility: rmandade de Santa Casa de Misericordia de Porto Alegre; Hospital Santa Rita
city: Mississauga
country: Canada
facility: Peel Regional Cancer Centre
state: Ontario
city: Mumbai
country: India
facility: Department of Atomic Energy (DAE); Tata Memorial Centre (TMC); Tata
city: Seoul
country: Korea, Republic of
facility: National Cancer Center
city: Skopje
country: Macedonia, The Former Yugoslav Republic of
facility: Radiotherapy and Oncology University Clinic
city: Rabat
country: Morocco
facility: Institut National d'Oncologie
city: Bahawalpur
country: Pakistan
facility: Bahawalpur Institute of Nuclear Medicine and Oncology (BINO)
city: Lima
country: Peru
facility: Instituto Nacional de Enfermedades Neoplásicas
city: Cape Town
country: South Africa
facility: Department of Radiation Oncology, Groote Schuur Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital; NHS Trust
Study officials:
affiliation: International Atomic Energy Agency (IAEA)
name: Eduardo H. Zubizarreta, M.D.
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1016/s0360-3016(01)01755-2.
citation: 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. doi: 10.1016/s0360-3016(00)00497-1.
citation: 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. doi: 10.1016/s0360-3016(98)00387-3.
citation: 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. doi: 10.1200/JCO.1999.17.5.1339.
citation: 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. doi: 10.1056/NEJM199904153401501.
citation: 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. doi: 10.1016/S0140-6736(01)05965-7.
citation: 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. doi: 10.1200/JCO.2002.20.4.966.