Clinical trial NCT01223248: Randomized Study Comparing Two Dosing Schedules for Hypofractionated Image-Guided Radiation Therapy
Official title: A Phase III Randomized Study Comparing Two Dosing Schedules for Hypofractionated Image-Guided Radiation Therapy in Patients With Metastatic Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Melanoma
Ovarian Cancer
Sarcoma
Bone
CNS-Spinal CD/MEMBR, NOS
Lymph Nodes
Soft Tissue
Keywords: radiation
Hypofractionated Image- Guided
IGIMRT
RT
10-154
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: University of Pisa
name: University of California, San Francisco
name: The Champalimaud Centre, Lisbon, Portugal
First posted: 2010-10-18
Enrollment: 220
Sex: ALL
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 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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."

Primary outcomes:
measure: To compare the loco-regional control rates of two established hypo-fractionated radiation treatment regimens
timeFrame: 2 years
Secondary outcomes:
measure: To compare toxicity outcomes
timeFrame: 2 years
measure: To compare patterns of failure between these two cohorts.
timeFrame: 2 years
measure: To look at changes in SUV uptake as a measure of tumor response.
timeFrame: 2 years
measure: changes in tumor perfusion
timeFrame: 2 years
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Pisa
country: Italy
facility: University of Pisa
city: Lisbon
country: Portugal
facility: The Champalimaud Centre
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Yoshiya Yamada, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.