CRP on Radiobiological and Clinical Studies on Viral-Induced Cancer's Response to Radiotherapy

Cervix Cancer Clinical Trial

Official title:

CRP on Radiobiological and Clinical Studies on Viral-induced Cancer's Response to Radiotherapy With Comprehensive Morbidity Assessment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00122772
• Other study ID #: E33026
• Status: Completed
• Phase: Phase 3
• First received: July 19, 2005
• Last updated: October 13, 2011
• Start date: November 2005
• Est. completion date: June 2010

Study information

• Verified date: October 2011
• Source: International Atomic Energy Agency
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Nations: International Atomic Energy Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 601
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cervix Cancer
• Uterine Cervical Neoplasms

Intervention

Radiation:
• Radiotherapy
External Beam Radiation 46Gy in 23 daily fractions High Dose Brachytherapy 2 fractions of 9Gy
• Radiotherapy
External Beam Radiotherapy 46Gy in 23 daily fractions High Dose Brachytherapy 4 fractions of 7Gy
• Radiotherapy/Cisplatin
External Beam Radiation 46Gy in 23 daily fractions High Dose Brachytherapy 2 fractions of 9Gy Cisplatin 40 mg/sqm weekly
• Radiotherapy/Cisplatin
External Beam Radiotherapy 46Gy in 23 daily fractions High Dose Brachytherapy 4 fractions of 7Gy Cisplatin 40mg/sqm weekly

Locations

Country	Name	City	State
Austria	University of Vienna; Department of Radiotherapy and Radiobiology	Vienna
Brazil	rmandade de Santa Casa de Misericordia de Porto Alegre; Hospital Santa Rita	Porto Alegre
Canada	Peel Regional Cancer Centre	Mississauga	Ontario
India	Department of Atomic Energy (DAE); Tata Memorial Centre (TMC); Tata	Mumbai
Korea, Republic of	National Cancer Center	Seoul
Macedonia, The Former Yugoslav R	Radiotherapy and Oncology University Clinic	Skopje
Morocco	Institut National d'Oncologie	Rabat
Pakistan	Bahawalpur Institute of Nuclear Medicine and Oncology (BINO)	Bahawalpur
Peru	Instituto Nacional de Enfermedades Neoplásicas	Lima
South Africa	Department of Radiation Oncology, Groote Schuur Hospital	Cape Town
United Kingdom	Christie Hospital; NHS Trust	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
International Atomic Energy Agency

Countries where clinical trial is conducted

Austria,  Brazil,  Canada,  India,  Korea, Republic of,  Macedonia, The Former Yugoslav Republic of,  Morocco,  Pakistan,  Peru,  South Africa,  United Kingdom, 

References & Publications (7)

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. — View 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. — View 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. Erratum in: Int J Radiat Oncol Biol Phys 2002 Mar 15;52(4):1157. — View 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. — View 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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Outcome		5 years	No
Primary	Treatment Toxicity		3 months	Yes
Primary	Molecular markers that will predict tumor control/resistance		5 years	No
Primary	Whether E6 and E7 viral proteins predict cellular radiosensitivity in oxic and hypoxic conditions in vitro and tumor control/resistance in vivo		5 years	No
Primary	Effectiveness of a questionnaire template on a computer in face-to-face interviews in a multicentre multinational study.		2 years	No

External Links

•   International Atomic Energy Agency, Research Contracts Administration