Randomized Study Comparing Two Dosing Schedules for Hypofractionated Image-Guided Radiation Therapy

NCT01223248 | Active Not Recruiting Phase 3

• 1 other identifier: 10-154
• Study Type: interventional
• Target: 220
• Locations: 3 countries
• Sites: 4

Brief Summary

The purpose of this study is to find out which way of giving high-dose radiation works best for treatment of cancer that has spread to bone, the spine, soft tissue, or lymph nodes. This study will look at the effects, good and/or bad, of giving 27 Gy in three fractions (3 days) or 24 Gy in one fraction (1 day) using image-guided intensity-modulated radiotherapy (IG-IMRT). IG-IMRT is radiation that is given directly to the cancer site and reduces the exposure to normal tissue. Currently there are no studies that compare the effects of giving radiation in either hypofractionated doses (higher total doses of radiation spread out over several treatment days) or a single-fraction dose (entire radiation dose given in one treatment session). The patient may be asked to participate in an additional part of this study where we will get a a (DW/DCE) MRI before treatment start and within one hour after radiation treatment. If the patient is asked to take part in this portion of the study, all they will need to do is get up to 3 MRIs with standard contrast injection. The purpose of this is to see if as a result of the treatment there are changes in the blood flow going to the cancer which could suggest that the treatment may be successful. In addition some patients can present new lesions and may be asked if they would like to have these new lesions treated on the protocol. If they are given this option, this will not extend their follow up period. The follow up of the new lesions will match with the prior follow up dates.

Conditions

Melanoma; Ovarian Cancer; Sarcoma; Bone; CNS-Spinal CD/MEMBR, NOS; Lymph Nodes; Soft Tissue

Keywords

radiation; Hypofractionated Image- Guided; IGIMRT; RT; 10-154

Outcome Measures

Primary Outcomes (1)

• To compare the loco-regional control rates of two established hypo-fractionated radiation treatment regimens

  a single dose of 24 Gy versus 27 Gy in three fractions for patients with metastatic disease

  2 years

Secondary Outcomes (4)

• To compare toxicity outcomes

  2 years

• To compare patterns of failure between these two cohorts.

  2 years

• To look at changes in SUV uptake as a measure of tumor response.

  2 years

• changes in tumor perfusion

  2 years

Study Arms (2)

stereotactic IGIMRT using a single dose of 24 Gy

EXPERIMENTAL

This is a phase III, multicenter, randomized, study comparing two dosing schedules for hypofractionated image-guided radiation therapy to bone, spine, soft tissue, and lymph nodes in patients with metastatic disease

Radiation: IGIMRT using a single dose of 24 Gy

stereotactic IGIMRT 27 Gy in 3 fractions

EXPERIMENTAL

This is a phase III, multicenter, randomized, study comparing two dosing schedules for hypofractionated image-guided radiation therapy to bone, spine, soft tissue, and lymph nodes in patients with metastatic disease

Radiation: IGIMRT 27 Gy in 3 fractions

Interventions

IGIMRT using a single dose of 24 Gy RADIATION

Pts in both the hypofractionated \& single dose arms will receive the same following standard procedures. The only difference between the arms is the dose delivered at each treatment. 20 MSKCC pts (10 per treatment arm) will be accrued to undergo baseline DW-MRI \& DCE-MRI pretreatment for both arms \& 1 hour after their initial treatment for single fraction pts, \& within one hour of their initial \& final radiation treatment for the hypofractionated pts. Pts will be considered for this scan based on compliance to scan schedule \& MRI availability for performing the scan within one hour of the planned IGRT. 24 MSKCC pts (12 per treatment arm) will be accrued for the blood collection (optional) up to 4 hours prior, 50-90 minutes after, \& approximately 24 hours \[MCPG2.3\]after treatment for single fraction pts. For pts partaking in both sub-studies, the post-treatment blood collection may be done in a 50-120 minute window to account for scheduling conflicts with the research MRI.

stereotactic IGIMRT using a single dose of 24 Gy

IGIMRT 27 Gy in 3 fractions RADIATION

Pts in both the hypofractionated \& single dose arms will receive the same following standard procedures. The only difference between the arms is the dose delivered at each treatment. 20 MSKCC pts (10 per treatment arm) will be accrued to undergo baseline DW-MRI \& DCE-MRI pretreatment for both arms \& within 1 hour after their initial treatment for single fraction pts, \& within one hour of their initial \& final radiation treatment for the hypofractionated pts. Pts will be considered for this scan based on compliance to scan schedule \& MRI availability for performing the scan within one hour of the planned IGRT. 24 MSKCC pts (12 per treatment arm) will be accrued for the blood collection (optional) up to 4 hours prior, 50-90 minutes after, \& approximately 24 hours \[MCPG2.3\]after treatment for single fraction pts. For pts partaking in both sub-studies, the post-treatment blood collection may be done in a 50-120 minute window to account for scheduling conflicts with the research MRI.

stereotactic IGIMRT 27 Gy in 3 fractions

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of cancer (including epithelial carcinoma, sarcoma, and melanoma) The diagnosis can be done at MSKCC or at participating institutions.
• Sites of metastatic disease to be treated on protocol are limited to bone, spine, soft tissue, and lymph nodes only.
• Patients with American Joint Committee on Cancer (6th edition, 2002) Stage IV cancer with distant metastases
• Age 18 years or older
• Life expectancy \>3 months
• Maximum tumor dimension of ≤6 cm in lymph nodes, soft tissue, osseous metastases, or spinal metastases seen on imaging (computed tomography \[CT\], magnetic resonance imaging \[MRI\], or PET/CT) and considered amenable for RT.
• If the lesion(s) to be treated are soft-tissue or lymph Nodes unidimensionally measurable disease is required. Bone \& spine lesions are eligible even if considered non-measurable.
• Measurable disease is defined as:
• ≥ 10mm for soft-tissue lesions
• ≥ 15mm on the short axis of lymph nodes
• KPS ≥ 80
• Patients must have normal bone marrow function as defined below:(within 2 months of registration) Hemoglobin ≥9.0 g/dl Absolute neutrophil count (ANC) ≥1,500/μl Platelets ≥100,000/μl

You may not qualify if:

• Prior radiotherapy delivered to the target region
• Disease to be treated on protocol is less than 2 mm from the spinal cord and therefore will not meet dose constraints\*
• Pregnancy or Breast-Feeding (Participants of child-bearing potential are eligible but must consent to using effective contraception during therapy and for at least 3 months after completing therapy).
• Chemotherapy given on the day of the planned radiotherapy treatment
• Lesions which comprise \>70% of the width of weight bearing bones, such as the femur.
• Existing cortical bone destruction, where orthopedic stabilization would be required.
• Areas to be treated on protocol do not include metastases to liver, brain or lung.
• Note: Patients with eligible and ineligible lesions will be accrued to this protocol. Only target eligible lesions will be treated per protocol. Other eligible and ineligible lesions will be treated at the discretion of the treating physician."

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• University of Pisa: collaborator
• University of California, San Francisco: collaborator
• The Champalimaud Centre, Lisbon, Portugal: collaborator

Study Sites (4)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pisa

Pisa, Italy

Location

The Champalimaud Centre

Lisbon, Portugal

Location

Related Publications (2)

• Zelefsky MJ, Yamada Y, Greco C, Lis E, Schoder H, Lobaugh S, Zhang Z, Braunstein S, Bilsky MH, Powell SN, Kolesnick R, Fuks Z. Phase 3 Multi-Center, Prospective, Randomized Trial Comparing Single-Dose 24 Gy Radiation Therapy to a 3-Fraction SBRT Regimen in the Treatment of Oligometastatic Cancer. Int J Radiat Oncol Biol Phys. 2021 Jul 1;110(3):672-679. doi: 10.1016/j.ijrobp.2021.01.004. Epub 2021 Jan 8.

  PMID: 33422612 DERIVED

• Bodo S, Campagne C, Thin TH, Higginson DS, Vargas HA, Hua G, Fuller JD, Ackerstaff E, Russell J, Zhang Z, Klingler S, Cho H, Kaag MG, Mazaheri Y, Rimner A, Manova-Todorova K, Epel B, Zatcky J, Cleary CR, Rao SS, Yamada Y, Zelefsky MJ, Halpern HJ, Koutcher JA, Cordon-Cardo C, Greco C, Haimovitz-Friedman A, Sala E, Powell SN, Kolesnick R, Fuks Z. Single-dose radiotherapy disables tumor cell homologous recombination via ischemia/reperfusion injury. J Clin Invest. 2019 Feb 1;129(2):786-801. doi: 10.1172/JCI97631. Epub 2019 Jan 14.

  PMID: 30480549 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Melanoma; Ovarian Neoplasms; Sarcoma; Pyloric Stenosis, Hypertrophic

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Connective and Soft Tissue; Pyloric Stenosis; Gastric Outlet Obstruction; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• Yoshiya Yamada, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2010
• First Posted: October 18, 2010
• Study Start: October 1, 2010
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: November 4, 2025

Record last verified: 2025-11

Locations

PT (1); IT (1); US (2)