Optimization of Radiotherapy in Treatment of Painful Bone Metastasis

Pain Clinical Trial

— bone mets  

Official title:

Investigation of Optimal Radiotherapy Regimen and Type of Irradiation in Treatment of Painful Bone Metastasis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00610272
• Other study ID #: E33028
• Status: Completed
• Phase: Phase 3
• First received: January 25, 2008
• Last updated: August 6, 2013
• Start date: January 2008
• Est. completion date: August 2012

Study information

• Verified date: August 2013
• 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

Bone metastasis is one of the most frequent end complications of the cancer. Radiation therapy is the mainstay of treatment in this disease. Single fraction radiotherapy in both single and multiple bone metastasis is widely used, but optimization of the single dose fractionation is needed. Two different regimens of radiotherapy dose fractionation will be investigated in both single and multiple bone metastasis and endpoints will include pain relief as well as toxicity and quality of life.

Description:

PROTOCOL SCHEMA

Group A Treatment of single site of painful bone metastasis:

Arm 1: 4 Gy single fraction; mandate first retreatment if moderate or severe pain persists or recurs (as measured by categorical pain scale or VAS greater than 50 mm), >4 weeks after initial RT) retreat with 8 Gy single fraction; second retreatment is optional if moderate or severe pain recurs (as measured by categorical pain scale or VAS greater than 50 mm), retreat with 8 Gy after > 4 weeks

Arm 2: 8 Gy single fraction, mandate first retreatment if moderate or severe pain persists or recurs (as measured by categorical pain scale or VAS greater than 50 mm), >4 weeks after initial RT) retreat with 8 Gy single fraction; second retreatment is optional if moderate or severe pain recurs (as measured by categorical pain scale or VAS greater than 50 mm), retreat with 8 Gy after > 4 weeks

Group B Treatment of multiple bone metastasis: lower hemibody radiotherapy (LHBI):

Arm 3: 8 Gy in a single fraction; retreatments > 4 weeks, using local RT fields to sites of residual or recurrent, moderate or severe pain with a single fraction of 8 Gy) ; second reirradiation with 8 Gy using local RT fields optional (at discretion of PI);

Arm 4: 12 Gy in 4 fractions of 3 Gy in 2 consecutive days interfraction interval of a minimum of 6 hrs; retreatments > 4 weeks using local RT fields to sites of residual or recurrent, moderate or severe pain with a single fraction of 8 Gy); second reirradiation with 8 Gy using local RT fields optional (at discretion of PI) ;

Recruitment information / eligibility

• Status: Completed
• Enrollment: 650
• Est. completion date: August 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• histological diagnosis of malignancy associated with radiological evidence of painful bone metastasis

• If patients with two sites of pain requiring separate treatment are to be entered, the same randomized treatment option will be used for both sites, but response at each site will be scored and analyzed separately.

• age > 18 years

• anticipated remaining life of at least 12 weeks (3 months)

• informed consent

Exclusion Criteria:

• Primary histology myeloma

• Sites of previous RT or previous radioisotope treatment

• conditions or circumstances, which may interfere with treatment or follow-up

• complicated bone metastasis (pathological fractures, metastatic spinal cord compression)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bone Marrow Diseases
• Bone Metastasis
• Bone Neoplasms
• Neoplasm Metastasis
• Pain

Intervention

Radiation:
• Radiotherapy
4 Gy single fraction; mandate first retreatment if moderate or severe pain persists or recurs (as measured by categorical pain scale or VAS greater than 50 mm), >4 weeks after initial RT) retreat with 8 Gy single fraction; second retreatment is optional if moderate or severe pain recurs (as measured by categorical pain scale or VAS greater than 50 mm), retreat with 8 Gy after > 4 weeks
• Radiotherapy
8 Gy single fraction, mandate first retreatment if moderate or severe pain persists or recurs (as measured by categorical pain scale or VAS greater than 50 mm), >4 weeks after initial RT) retreat with 8 Gy single fraction; second retreatment is optional if moderate or severe pain recurs (as measured by categorical pain scale or VAS greater than 50 mm), retreat with 8 Gy after > 4 weeks
• Radiotherapy
8 Gy in a single fraction; retreatments > 4 weeks, using local RT fields to sites of residual or recurrent, moderate or severe pain with a single fraction of 8 Gy) ; second reirradiation with 8 Gy using local RT fields optional (at discretion of PI);
• Radiotherapy
12 Gy in 4 fractions of 3 Gy in 2 consecutive days interfraction interval of a minimum of 6 hrs; retreatments > 4 weeks using local RT fields to sites of residual or recurrent, moderate or severe pain with a single fraction of 8 Gy); second reirradiation with 8 Gy using local RT fields optional (at discretion of PI) ;

Locations

Country	Name	City	State
Algeria	Centre Pierre et Marie Curie, Centre hospitalier universitaire Mustapha (CHU)	Alger
Brazil	Irmandade de Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Egypt	Misr Oncology Center (MOC)	Cairo
India	Tata Memorial Hospital	Mumbai
Lithuania	Institute of Oncology, University of Vilinius	Vilnius
Macedonia, The Former Yugoslav R	Institute of Radiotherapy and Oncology	Skopje
Mexico	Instituto Nacional de Cancerología (INCAN)	Ciudad de Mexico
Serbia	Institute of Oncology and Radiology	Belgrade
Spain	Hospital Clinic Universidad de Barcelona	Barcelona
Spain	Hospital Son Dureta	Palma de Mallorca
Tunisia	Institut national de cancer Salah Azaiz	Tunis
United Kingdom	Mount Vernon Cancer Centre	Northwood

Sponsors (1)

Lead Sponsor	Collaborator
International Atomic Energy Agency

Countries where clinical trial is conducted

Algeria,  Brazil,  Egypt,  India,  Lithuania,  Macedonia, The Former Yugoslav Republic of,  Mexico,  Serbia,  Spain,  Tunisia,  United Kingdom, 

References & Publications (7)

Arcangeli G, Micheli A, Arcangeli G, Giannarelli D, La Pasta O, Tollis A, Vitullo A, Ghera S, Benassi M. The responsiveness of bone metastases to radiotherapy: the effect of site, histology and radiation dose on pain relief. Radiother Oncol. 1989 Feb;14(2):95-101. — View Citation

Gaze MN, Kelly CG, Kerr GR, Cull A, Cowie VJ, Gregor A, Howard GC, Rodger A. Pain relief and quality of life following radiotherapy for bone metastases: a randomised trial of two fractionation schedules. Radiother Oncol. 1997 Nov;45(2):109-16. Review. — View Citation

Hoskin PJ, Price P, Easton D, Regan J, Austin D, Palmer S, Yarnold JR. A prospective randomised trial of 4 Gy or 8 Gy single doses in the treatment of metastatic bone pain. Radiother Oncol. 1992 Feb;23(2):74-8. — View Citation

Mithal NP, Needham PR, Hoskin PJ. Retreatment with radiotherapy for painful bone metastases. Int J Radiat Oncol Biol Phys. 1994 Jul 30;29(5):1011-4. — View Citation

Salazar OM, DaMotta NW, Bridgman SM, Cardiges NM, Slawson RG. Fractionated half-body irradiation for pain palliation in widely metastatic cancers: comparison with single dose. Int J Radiat Oncol Biol Phys. 1996 Aug 1;36(1):49-60. — View Citation

Salazar OM, Sandhu T, da Motta NW, Escutia MA, Lanzós-Gonzales E, Mouelle-Sone A, Moscol A, Zaharia M, Zaman S. Fractionated half-body irradiation (HBI) for the rapid palliation of widespread, symptomatic, metastatic bone disease: a randomized Phase III trial of the International Atomic Energy Agency (IAEA). Int J Radiat Oncol Biol Phys. 2001 Jul 1;50(3):765-75. — View Citation

Wu JS, Wong R, Johnston M, Bezjak A, Whelan T; Cancer Care Ontario Practice Guidelines Initiative Supportive Care Group. Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys. 2003 Mar 1;55(3):594-605. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain Relief (response rate) at 4 weeks		Up to 52 weeks	No
Secondary	Onset and Duration of Pain Relief in Responders		Up to 52 weeks	No
Secondary	Toxicity		Up to 52 weeks	Yes
Secondary	Quality of Life		Up to 52 weeks	No
Secondary	Rates of Pathological Fractures and Spinal Cord Compression		Up to 52 weeks	No