MelanomaPhase 3NCT01223248
Randomized Study Comparing Two Dosing Schedules for Hypofractionated Image-Guided Radiation Therapy
A Phase 3 study testing IGIMRT using a single dose of 24 Gy and IGIMRT 27 Gy in 3 fractions in people with Melanoma and Ovarian Cancer, run by Memorial Sloan Kettering Cancer Center at 4 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Ovarian Cancer, Sarcoma
- What is being tested?
- IGIMRT using a single dose of 24 Gy and IGIMRT 27 Gy in 3 fractions
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 220 participants
- Where
- 4 sitesin 3 countries
- Study dates
- Oct 2010to Oct 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 12Show fewer
- 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
Who cannot join
- 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."
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
United States2 sites
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of California San Francisco
San Francisco, California, 94143
About this study
Official title: A Phase III Randomized Study Comparing Two Dosing Schedules for Hypofractionated Image-Guided Radiation Therapy in Patients With Metastatic Cancer
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
- Being tested
- IGIMRT using a single dose of 24 Gy, IGIMRT 27 Gy in 3 fractions
- Keywords
- radiation, Hypofractionated Image- Guided, IGIMRT, RT, 10-154
- Medical subject headings
- Melanoma, Ovarian Neoplasms, Sarcoma, Pyloric Stenosis, Hypertrophic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IGIMRT using a single dose of 24 GyRadiation
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.
IGIMRT 27 Gy in 3 fractionsRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Radiation: IGIMRT 27 Gy in 3 fractions |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years
Secondary outcomes (4)
To compare toxicity outcomes
Measured: 2 years
To compare patterns of failure between these two cohorts.
Measured: 2 years
To look at changes in SUV uptake as a measure of tumor response.
For patients who are followed with PET/CTs
Measured: 2 years
changes in tumor perfusion
resulting from high-dose IGRT for patients treated with this approach to focal metastases using dynamic contrast-enhanced (DCE)-MRI.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2010 (estimated)
- Study startOct 2010
- Primary completionOct 2026 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 220 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pisa, University of California, San Francisco, The Champalimaud Centre, Lisbon, Portugal
- Responsible party
- Sponsor
- Investigators
- Yoshiya Yamada, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01223248
- Sponsor's protocol ID
- 10-154
- Status last verified
- Nov 2025
- First submitted
- 14 Oct 2010
- Last updated
- 4 Nov 2025
- Results posted
- No
Publications
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.
PubMed 33422612Bodo 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.
PubMed 30480549
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomized Study Comparing Two Dosing Schedules for Hypofractionated Image-Guided Radiation Therapy in Patients With Metastatic Cancer
- ClinicalTrials.gov ID
- NCT01223248
- Acronym / sponsor ID
- 10-154
- Conditions
- Melanoma, Ovarian Cancer, Sarcoma, Bone, CNS-Spinal CD/MEMBR, NOS, Lymph Nodes
- Keywords
- radiation, Hypofractionated Image- Guided, IGIMRT, RT, 10-154
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 220 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- University of Pisa, University of California, San Francisco, The Champalimaud Centre, Lisbon, Portugal
- Study start
- Oct 2010 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 18 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| stereotactic IGIMRT using a single dose of 24 Gy | Experimental | Radiation: IGIMRT using a single dose of 24 GyThis 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 |
| stereotactic IGIMRT 27 Gy in 3 fractions | Experimental | Radiation: IGIMRT 27 Gy in 3 fractionsThis 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IGIMRT using a single dose of 24 GyPts 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. | Radiation | stereotactic IGIMRT using a single dose of 24 Gy |
| IGIMRT 27 Gy in 3 fractionsPts 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. | Radiation | stereotactic IGIMRT 27 Gy in 3 fractions |
Primary outcome
To compare the loco-regional control rates of two established hypo-fractionated radiation treatment regimens
Time frame: 2 years
a single dose of 24 Gy versus 27 Gy in three fractions for patients with metastatic disease
4 secondary outcomes
To compare toxicity outcomes
Time frame: 2 years
To compare patterns of failure between these two cohorts.
Time frame: 2 years
To look at changes in SUV uptake as a measure of tumor response.
Time frame: 2 years
changes in tumor perfusion
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2025.
- Derived from this study: PubMed 33422612Zelefsky 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.
- Derived from this study: PubMed 30480549Bodo 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.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yoshiya Yamada, MD principal investigator
Memorial Sloan Kettering Cancer Center
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing IGIMRT using a single dose of 24 Gy and IGIMRT 27 Gy in 3 fractions in people with Melanoma and Ovarian Cancer, run by Memorial Sloan Kettering Cancer Center at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Italy, Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To compare the loco-regional control rates of two established hypo-fractionated radiation treatment regimens (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01223248, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2025.