Metastatic Bone TumorPhase 31-2 PUNCHNCT05115331
Palliative UNConventional Hypofractionation Trial for Metastatic Bone Disease
A Phase 3 study testing Experimental Radiation Dose and Conventional Radiation Dose in people with Metastatic Bone Tumor, run by University of Cincinnati at 1 site in United States.
Trial summary
This is a randomized Phase III study evaluating the efficacy of hypofractionated and dose-escalated palliative radiation therapy in metastatic bone disease (MBD). Patients will be randomized 1:1 to the conventional (8 Gy in a single fraction) and experimental (16 Gy in 2 fractions) groups with baseline and subsequent… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Bone Tumor
- What is being tested?
- Experimental Radiation Dose and Conventional Radiation Dose
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 168 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Nov 2021to 24 Nov 2025
- 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
- Patients must have histologically or cytologically confirmed history of solid cancer malignancy (including small cell lung cancer).
- Patients must have 1-3 new or newly painful metastatic lesions to bone as defined by CT scan, MRI, or PET scan. Lesions must be located in a long bone, pelvis/hip, spine, sacrum, or ribs. A lesion is "new" if it has occurred since any previous imaging, or if new cancer diagnosis, or new at presentation. A newly painful lesion is one that had been visible on previous imaging, but was either asymptomatic or minimally painful so that no treatment was pursued.
- There must be clearly attributable pain associated with the 1-3 new metastatic bone lesion(s) as documented on the Brief Pain Inventory and per investigator's determination that these imaging findings are consistent with the patient's described BPI pain from metastatic lesion(s).
- Age ≥18 years.
- ECOG performance status ≤3 or (Karnofsky ≥40%, see Appendix A).
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial in the opinion of the investigator.
- Ability to understand and the willingness to sign written informed consent.
Who cannot join
- Patients who have had or will have chemotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to commencing study RT. Patients undergoing treatment with hormonal or endocrine therapies will be eligible for this trial and may continue these through study radiotherapy.
- Patients with widespread metastatic disease, such that in the opinion of the PI would preclude an investigator from determining the origin of bone disease-related pain and/or response to palliative treatment.
- Patients who are receiving any other investigational agents. Patients who have received other investigational agents previously who are no longer receiving these investigational agents may be eligible at the discretion of the PI.
- Patients with complicated bone metastases, defined as having at least one or more of the following criteria:
- Nerve root compression
- Prior radiation to the spinal cord at that bone level
Show all 15Show fewer
- Impending (score of 9 or more on Mirel's Criteria) or existing pathologic fracture
- Spinal cord compression
- cauda equina syndrome
- Patients who have been previously radiated to the primary anatomic site for which they are being considered for this trial, or have had surgical fixation of the site. However, patients may have undergone previous courses of radiotherapy to a primary site or separate site of metastatic disease if in the opinion of the investigator the patient will be able to tolerate palliative RT.
- Patients with uncontrolled intercurrent illness.
- Pregnant women are excluded from this study.
- Life expectancy of under 3 months in the opinion of the treating investigator.
- Liquid malignancies, including myeloma, lymphoma.
- Judgment by the investigator that the patient is unsuitable to participate in the study or the patient is unlikely to comply with study procedures, restrictions and requirements.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 1-2 PUNCH: Palliative UNConventional Hypofractionation Trial for Metastatic Bone Disease
This is a randomized Phase III study evaluating the efficacy of hypofractionated and dose-escalated palliative radiation therapy in metastatic bone disease (MBD). Patients will be randomized 1:1 to the conventional (8 Gy in a single fraction) and experimental (16 Gy in 2 fractions) groups with baseline and subsequent assessment of both pain and quality of life metrics.
Read the detailed description
Metastatic Bone Disease (MBD) has been demonstrated to be a common clinical problem, and often presents with severe, if not debilitating pain. This often proceeds to affect a patient's emotional and even global functioning. Radiation therapy is an effective treatment commonly used in the palliation of these metastatic lesions, and improvements in QOL scores are associated with response to radiotherapy treatment. Although both 30 Gy/10 fractions and 8 Gy in a single fraction are considered standard of care in the palliative setting, single fraction treatment is associated with increased rates of local failure and retreatment. Considering that patients with MBD often have life-limiting disease, and frequently have great difficulty with undergoing extended radiotherapy treatments, there is a significant unmet need for palliative treatments that are effective, safe, timely, and provide a durable local tumor and pain control. The investigators hypothesize that utilizing a fractionation scheme with an escalated biologically equivalent dose will result in a higher proportion of patients responding to treatment, and will also lead to more durable responses.
- Conditions
- Metastatic Bone Tumor
- Being tested
- Experimental Radiation Dose, Conventional Radiation Dose
- Keywords
- Metastatic Bone Disease
- Medical subject headings
- Bone Neoplasms, Bone Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental Radiation DoseRadiation
16 Gy in 2 fractions
Conventional Radiation DoseRadiation
8 Gy in a single fraction
| Study group | Role | What they receive |
|---|---|---|
| Conventional Radiation Dose | Active comparator | 8 Gy in a single fraction Receives: Radiation: Conventional Radiation Dose |
| Experimental Radiation Dose | Experimental | 16 Gy in 2 fractions Receives: Radiation: Experimental Radiation Dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain Response measured by the Brief Pain Inventory
A primary objective evaluate the efficacy of the addition of a second 8 Gy fraction administered 1 week following the standard 8 Gy treatment currently utilized for palliation of symptomatic bone metastases in solid cancers, as measured by pain response at 1 month. The primary endpoint for this objective is pain response which will be determined using the Brief Pain Inventory (BPI) at one month.
Measured: 1 month post radiation completion.
Pain Response measured by the Bone Mets Pain scale
A primary objective evaluate the efficacy of the addition of a second 8 Gy fraction administered 1 week following the standard 8 Gy treatment currently utilized for palliation of symptomatic bone metastases in solid cancers, as measured by pain response at 1 month. The primary endpoint for this objective is pain response which will be classified using the International Consensus on Palliative Radiation for Future Trials on Bone Mets, which is a 4-point scale ranging from complete response to pain progression. Pain relief as measured by this scale and daily oral morphine equivalents (OME) will be graded at 1 month.
Measured: 1 month post radiation completion.
Safety through 30 days post-radiation
A second primary objective is to characterize the safety profile and adverse events (AE) of dose-escalated palliative radiotherapy. The primary endpoint for this objective is Adverse events will be described and coded based upon the NCI CTCAE v5.0 through 30 days after end of a subject's treatment.
Measured: 30 days post radiation completion.
Secondary outcomes (5)
Time to pain relief
A secondary objective is to determine time to maximal pain relief, and to determine pain response at 2, 3, and 6 months. Pain response at 2, 3, and 6 months will be assessed using the Brief Pain Inventory (BPI), and classified using the International Consensus on Palliative Radiation for Future Trials on Bone Mets; as well as daily oral morphine equivalents (OME). Time to maximal pain relief will be determined from BPI questionnaires and International Consensus on Palliative Radiation for Future Trials on Bone Mets scale data.
Measured: 2, 3, and 6 months after completion of radiation treatment.
Quality of Life (EORTC QLQ-C30) at Baseline, 1, 3, and 6 months post treatment
Another secondary objective is to evaluate the impact of standard and dose-escalated arms of palliative radiotherapy on quality of life. Quality of life data will be obtained via European Organisation for Research and Treatment of Cancer Quality of Life Cancer Patients (EORTC QLQ-C30 (version 3)) at baseline and 1-, 3-, and 6-months post-treatment.
Measured: Baseline, 1, 3, and 6 months post radiation treatment.
Quality of Life (EORTC QLQBM22) at Baseline, 1, 3, and 6 months post treatment
Another secondary objective is to evaluate the impact of standard and dose-escalated arms of palliative radiotherapy on quality of life. Quality of life data will be obtained via European Organisation for Research and Treatment of Cancer Quality of Life Bone Metastases (EORTC QLQBM22) at baseline and 1-, 3-, and 6-months post-treatment.
Measured: Baseline, 1, 3, and 6 months post radiation treatment.
Overall survival through 2 years post-treatment.
Another secondary objective is to determine differences in overall survival between subjects receiving standard and dose-escalated palliative radiotherapy. Overall survival (OS) data from the date of completion of radiation therapy will be obtained from departmental records and electronic medical records through 2 years post end of radiation treatment.
Measured: 2 years post treatment.
Retreatment rates through 2 years post-treatment.
Another secondary objective is to determine differences in retreatment rates between subjects receiving standard and dose-escalated palliative radiotherapy. Retreatment rates data from the date of completion of radiation therapy will be obtained from departmental records and electronic medical records through 2 years post end of radiation treatment.
Measured: 2 years post treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2021
- Study start24 Nov 2021
- Primary completion13 Jul 2023
- Study completion24 Nov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Bone TumorStudies of the same condition, open and under way.
- 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 168 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Timothy Struve, University of Cincinnati
- Investigators
- Timothy Struve, MD, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05115331
- Sponsor's protocol ID
- UCCC-RT-21-01
- Acronym
- 1-2 PUNCH
- Status last verified
- May 2025
- First submitted
- 15 Oct 2021
- Last updated
- 31 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 1-2 PUNCH: Palliative UNConventional Hypofractionation Trial for Metastatic Bone Disease
- ClinicalTrials.gov ID
- NCT05115331
- Acronym / sponsor ID
- 1-2 PUNCH / UCCC-RT-21-01
- Conditions
- Metastatic Bone Tumor
- Keywords
- Metastatic Bone Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 168 participants (estimated)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Study start
- 24 Nov 2021 (actual)
- Primary completion
- 13 Jul 2023 (actual)
- Study completion
- 24 Nov 2025 (estimated)
- First posted
- 10 Nov 2021 (actual)
- 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.
This is a randomized Phase III study evaluating the efficacy of hypofractionated and dose-escalated palliative radiation therapy in metastatic bone disease (MBD). Patients will be randomized 1:1 to the conventional (8 Gy in a single fraction) and experimental (16 Gy in 2 fractions) groups with baseline and subsequent assessment of both pain and quality of life metrics.
Detailed description
Metastatic Bone Disease (MBD) has been demonstrated to be a common clinical problem, and often presents with severe, if not debilitating pain. This often proceeds to affect a patient's emotional and even global functioning. Radiation therapy is an effective treatment commonly used in the palliation of these metastatic lesions, and improvements in QOL scores are associated with response to radiotherapy treatment. Although both 30 Gy/10 fractions and 8 Gy in a single fraction are considered standard of care in the palliative setting, single fraction treatment is associated with increased rates of local failure and retreatment. Considering that patients with MBD often have life-limiting disease, and frequently have great difficulty with undergoing extended radiotherapy treatments, there is a significant unmet need for palliative treatments that are effective, safe, timely, and provide a durable local tumor and pain control. The investigators hypothesize that utilizing a fractionation scheme with an escalated biologically equivalent dose will result in a higher proportion of patients responding to treatment, and will also lead to more durable responses.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Conventional Radiation Dose | Active comparator | Radiation: Conventional Radiation Dose8 Gy in a single fraction |
| Experimental Radiation Dose | Experimental | Radiation: Experimental Radiation Dose16 Gy in 2 fractions |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients must have histologically or cytologically confirmed history of solid cancer malignancy (including small cell lung cancer).
- Patients must have 1-3 new or newly painful metastatic lesions to bone as defined by CT scan, MRI, or PET scan. Lesions must be located in a long bone, pelvis/hip, spine, sacrum, or ribs. A lesion is "new" if it has occurred since any previous imaging, or if new cancer diagnosis, or new at presentation. A newly painful lesion is one that had been visible on previous imaging, but was either asymptomatic or minimally painful so that no treatment was pursued.
- There must be clearly attributable pain associated with the 1-3 new metastatic bone lesion(s) as documented on the Brief Pain Inventory and per investigator's determination that these imaging findings are consistent with the patient's described BPI pain from metastatic lesion(s).
- Age ≥18 years.
- ECOG performance status ≤3 or (Karnofsky ≥40%, see Appendix A).
Key exclusion criteria (15 listed)
- Patients who have had or will have chemotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to commencing study RT. Patients undergoing treatment with hormonal or endocrine therapies will be eligible for this trial and may continue these through study radiotherapy.
- Patients with widespread metastatic disease, such that in the opinion of the PI would preclude an investigator from determining the origin of bone disease-related pain and/or response to palliative treatment.
- Patients who are receiving any other investigational agents. Patients who have received other investigational agents previously who are no longer receiving these investigational agents may be eligible at the discretion of the PI.
- Patients with complicated bone metastases, defined as having at least one or more of the following criteria:
- Patients who have been previously radiated to the primary anatomic site for which they are being considered for this trial, or have had surgical fixation of the site. However, patients may have undergone previous courses of radiotherapy to a primary site or separate site of metastatic disease if in the opinion of the investigator the patient will be able to tolerate palliative RT.
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 |
|---|---|---|
| Experimental Radiation Dose16 Gy in 2 fractions | Radiation | Experimental Radiation Dose |
| Conventional Radiation Dose8 Gy in a single fraction | Radiation | Conventional Radiation Dose |
Primary outcome
Pain Response measured by the Brief Pain Inventory
Time frame: 1 month post radiation completion.
A primary objective evaluate the efficacy of the addition of a second 8 Gy fraction administered 1 week following the standard 8 Gy treatment currently utilized for palliation of symptomatic bone metastases in solid cancers, as measured by pain response at 1 month. The primary endpoint for this objective is pain response which will be determined using the Brief Pain Inventory (BPI) at one month.
Pain Response measured by the Bone Mets Pain scale
Time frame: 1 month post radiation completion.
A primary objective evaluate the efficacy of the addition of a second 8 Gy fraction administered 1 week following the standard 8 Gy treatment currently utilized for palliation of symptomatic bone metastases in solid cancers, as measured by pain response at 1 month. The primary endpoint for this objective is pain response which will be classified using the International Consensus on Palliative Radiation for Future Trials on Bone Mets, which is a 4-point scale ranging from complete response to pain progression. Pain relief as measured by this scale and daily oral morphine equivalents (OME) will be graded at 1 month.
Safety through 30 days post-radiation
Time frame: 30 days post radiation completion.
A second primary objective is to characterize the safety profile and adverse events (AE) of dose-escalated palliative radiotherapy. The primary endpoint for this objective is Adverse events will be described and coded based upon the NCI CTCAE v5.0 through 30 days after end of a subject's treatment.
5 secondary outcomes
Time to pain relief
Time frame: 2, 3, and 6 months after completion of radiation treatment.
Quality of Life (EORTC QLQ-C30) at Baseline, 1, 3, and 6 months post treatment
Time frame: Baseline, 1, 3, and 6 months post radiation treatment.
Quality of Life (EORTC QLQBM22) at Baseline, 1, 3, and 6 months post treatment
Time frame: Baseline, 1, 3, and 6 months post radiation treatment.
Overall survival through 2 years post-treatment.
Time frame: 2 years post treatment.
Retreatment rates through 2 years post-treatment.
Time frame: 2 years post treatment.
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 31 May 2025.
- Individual participant dataSharing planned: No
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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.
Timothy Struve, MD principal investigator
University of Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Experimental Radiation Dose and Conventional Radiation Dose in people with Metastatic Bone Tumor, run by University of Cincinnati at 1 site in United States.
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 7 inclusion and 15 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 31 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Pain Response measured by the Brief Pain Inventory (time frame: 1 month post radiation completion.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 May 2025.