Clinical trial NCT05115331: Palliative UNConventional Hypofractionation Trial for Metastatic Bone Disease
Official title: 1-2 PUNCH: Palliative UNConventional Hypofractionation Trial for Metastatic Bone Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Metastatic Bone Tumor
Keywords: Metastatic Bone Disease
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
First posted: 2021-11-10
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

1. Patients must have histologically or cytologically confirmed history of solid cancer malignancy (including small cell lung cancer).
2. 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.
3. 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).
4. Age ≥18 years.
5. ECOG performance status ≤3 or (Karnofsky ≥40%, see Appendix A).
6. 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.
7. Ability to understand and the willingness to sign written informed consent.

Exclusion Criteria:

1. 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.
2. 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.
3. 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.
4. Patients with complicated bone metastases, defined as having at least one or more of the following criteria:

   1. Nerve root compression
   2. Prior radiation to the spinal cord at that bone level
   3. Impending (score of 9 or more on Mirel's Criteria) or existing pathologic fracture
   4. Spinal cord compression
   5. cauda equina syndrome
5. 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.
6. Patients with uncontrolled intercurrent illness.
7. Pregnant women are excluded from this study.
8. Life expectancy of under 3 months in the opinion of the treating investigator.
9. Liquid malignancies, including myeloma, lymphoma.
10. 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.

Primary outcomes:
measure: Pain Response measured by the Brief Pain Inventory
timeFrame: 1 month post radiation completion.
measure: Pain Response measured by the Bone Mets Pain scale
timeFrame: 1 month post radiation completion.
measure: Safety through 30 days post-radiation
timeFrame: 30 days post radiation completion.
Secondary outcomes:
measure: Time to pain relief
timeFrame: 2, 3, and 6 months after completion of radiation treatment.
measure: Quality of Life (EORTC QLQ-C30) at Baseline, 1, 3, and 6 months post treatment
timeFrame: Baseline, 1, 3, and 6 months post radiation treatment.
measure: Quality of Life (EORTC QLQBM22) at Baseline, 1, 3, and 6 months post treatment
timeFrame: Baseline, 1, 3, and 6 months post radiation treatment.
measure: Overall survival through 2 years post-treatment.
timeFrame: 2 years post treatment.
measure: Retreatment rates through 2 years post-treatment.
timeFrame: 2 years post treatment.
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Timothy Struve, MD
role: PRINCIPAL_INVESTIGATOR
References: