Shorter Radiation Therapy for Multiple Myeloma

Overseen By Yasmin Hasan, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Chicago

Must not be taking: Statins

Disqualifiers: Cardiovascular disease, Seizure disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This study if for people who have been diagnosed with multiple myeloma and their doctors are recommending radiation to help treat it. Typically, radiation consists of 2-3 weeks of external beam radiation therapy. Doctors leading this study would like to see if a shorter radiation course (i.e., hypofractionation) for pelvic radiation is safe for multiple myeloma. Because participants in this study will receive a shortened radiation course, each daily treatment dose that is delivered would be slightly higher than normal. This higher daily dose would be delivered because the study team would like to see if higher doses of radiation are as safe given over a shorter number of days compared to 2-3 weeks. The purpose of this study is to make sure that hypofractionation is safe and effective for individuals with multiple myeloma.

Will I have to stop taking my current medications?

The trial requires that participants do not receive any concurrent anti-myeloma or systemic therapy while participating. Additionally, if you have had prior cytotoxic chemotherapy, you must not receive that therapy within 2 weeks of starting radiation, and if you have had prior anti-cancer monoclonal antibody or other small molecules, you must not receive that therapy within 7 days of starting radiation.

What data supports the effectiveness of the treatment Hypofractionation, Hypofractionated Radiotherapy, Accelerated Radiotherapy for Multiple Myeloma?

Research on hypofractionated radiotherapy in breast and prostate cancer shows that it can be as effective as traditional radiation therapy, with shorter treatment times and similar outcomes. Additionally, studies in lung cancer and bone metastases suggest that this approach can be effective and safe, even for patients with complex conditions. ^{1 2 3 4 5}

Is hypofractionated radiation therapy generally safe for humans?

Hypofractionated radiation therapy has been studied for various conditions like prostate and breast cancer, showing it can be safe with careful planning and follow-up. However, there is a risk of severe tissue damage if not properly managed, especially when treating large areas or critical structures. ^{6 7 8 9 10}

How is the treatment Hypofractionation different from other treatments for multiple myeloma?

Hypofractionation is unique because it involves delivering larger doses of radiation over a shorter period, reducing the number of hospital visits compared to conventional radiation therapy. This approach has been shown to have comparable outcomes in other cancers, like breast cancer, and may offer a more convenient treatment schedule for patients. ^{1 11 12 13 14}

Research Team

Yasmin Hasan, MD

Principal Investigator

University of Chicago

Eligibility Criteria

This trial is for people with multiple myeloma who need radiation therapy. It's testing if a shorter course of higher-dose radiation (hypofractionation) over fewer days can be as safe and effective as the standard 2-3 week treatment.

Inclusion Criteria

Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study

I am not currently breastfeeding.

Participants must be able to give self-consent and then sign and date an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent in accordance with local regulatory and institutional guidelines before the performance of any protocol-related procedures that are not considered part of normal participant care

Exclusion Criteria

I haven't had significant radiation therapy to the area that's now being considered for treatment.

Participants must not have a history or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive hypofractionated radiation therapy with varying schedules from 1 to 10 daily treatments

1-2 weeks

Daily visits for radiation treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of side effects and adverse events

2 years

Regular follow-up visits for assessments

Treatment Details

Interventions

• Hypofractionation

Trial Overview The study is examining hypofractionated radiation therapy, which means giving larger doses of radiation in each session but reducing the total number of sessions. The goal is to see if this approach maintains safety and effectiveness.

Participant Groups

Group I: Group 4 - Dose Schedule 4 Experimental Treatment 1 Intervention

In this study, there will be 4 different radiation schedules, ranging from 1-10 daily treatments. Participants will be assigned to one of the dose schedules and they will know this ahead of time. The study doctor will tell each participant which study group and dose schedule they been assigned. For most participants, the actual time on the radiation treatment machine will be in the range of 30 to 60 minutes. The mold will be removed after the treatment. The number of treatments to each tumor will depend on which treatment group the participant is enrolled on: The longest possible treatment group would be 10 treatments in duration of about 2 weeks of treatment and the shortest possible treatment group would be 1 treatment.

Group II: Group 3 - Dose Schedule 3 Experimental Treatment 1 Intervention

In this study, there will be 4 different radiation schedules, ranging from 1-10 daily treatments. Participants will be assigned to one of the dose schedules and they will know this ahead of time. The study doctor will tell each participant which study group and dose schedule they been assigned. For most participants, the actual time on the radiation treatment machine will be in the range of 30 to 60 minutes. The mold will be removed after the treatment. The number of treatments to each tumor will depend on which treatment group the participant is enrolled on: The longest possible treatment group would be 10 treatments in duration of about 2 weeks of treatment and the shortest possible treatment group would be 1 treatment.

Group III: Group 2 - Dose Schedule 2 Experimental Treatment 1 Intervention

In this study, there will be 4 different radiation schedules, ranging from 1-10 daily treatments. Participants will be assigned to one of the dose schedules and they will know this ahead of time. The study doctor will tell each participant which study group and dose schedule they been assigned. For most participants, the actual time on the radiation treatment machine will be in the range of 30 to 60 minutes. The mold will be removed after the treatment. The number of treatments to each tumor will depend on which treatment group the participant is enrolled on: The longest possible treatment group would be 10 treatments in duration of about 2 weeks of treatment and the shortest possible treatment group would be 1 treatment.

Group IV: Group 1 - Dose Schedule 1 Experimental Treatment 1 Intervention

In this study, there will be 4 different radiation schedules, ranging from 1-10 daily treatments. Participants will be assigned to one of the dose schedules and they will know this ahead of time. The study doctor will tell each participant which study group and dose schedule they been assigned. For most participants, the actual time on the radiation treatment machine will be in the range of 30 to 60 minutes. The mold will be removed after the treatment. The number of treatments to each tumor will depend on which treatment group the participant is enrolled on: The longest possible treatment group would be 10 treatments in duration of about 2 weeks of treatment and the shortest possible treatment group would be 1 treatment.

Hypofractionation is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Hypofractionation for:

• Soft tissue sarcomas
• Extremity soft tissue sarcomas
• Trunk soft tissue sarcomas

Approved in United States as Hypofractionation for:

• Soft tissue sarcomas
• Extremity soft tissue sarcomas
• Trunk soft tissue sarcomas

Approved in Canada as Hypofractionation for:

• Soft tissue sarcomas
• Extremity soft tissue sarcomas
• Trunk soft tissue sarcomas

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Findings from Research

Hypofractionated whole breast irradiation (WBI) has been shown to produce outcomes comparable to conventional radiation in early-stage breast cancer patients, suggesting it is a safe and effective treatment option.

Current trials, including a phase III study by the Radiation Therapy Oncology Group, are investigating the feasibility and effectiveness of adding a concurrent tumor bed boost to hypofractionated WBI, which may enhance treatment outcomes and broaden its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated fractionation with a concurrent boost for early stage breast cancer. Freedman, GM., White, JR., Arthur, DW., et al.[2022]

Hypofractionated radiotherapy, which delivers higher doses of radiation in fewer sessions, may offer better therapeutic outcomes for breast and prostate cancers due to the unique properties of these tumors.

Recent clinical trials have been conducted to evaluate the effectiveness of hypofractionation, showing promising results, although there are limitations to this treatment approach that need to be considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Breast and Prostate Cancer by Hypofractionated Radiotherapy: Potential Risks and Benefits. Ray, KJ., Sibson, NR., Kiltie, AE.[2019]

A study of 380 breast cancer patients treated with a short hypofractionated radiotherapy schedule showed very low local relapse rates, with only 0.2% at 2 years and 2% at 5 years, indicating high efficacy.

The treatment also resulted in excellent overall survival rates of 97.4% at 2 years and 95% at 5 years, suggesting that this short radiotherapy schedule is a safe and effective alternative to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ten Daily Fractions for Whole Breast Cancer Irradiation: Long Term Results. Belgioia, L., Fozza, A., Trapani, L., et al.[2021]

In a study of 60 medically inoperable patients with stage I non-small-cell lung cancer, accelerated hypofractionated radiotherapy showed good local control with a 5-year local failure rate of only 20%.

The treatment was well tolerated, with no patients experiencing severe side effects like grade 3 or greater pneumonitis or esophagitis, making it a viable alternative when other treatments like stereotactic body radiation therapy are not possible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of accelerated hypofractionated radiotherapy in stage i non-small-cell lung cancer. Yung, T., Giuliani, ME., Le, LW., et al.[2021]

In a phase II clinical trial involving 50 patients with complicated bone metastases, hypofractionated radiotherapy (16 Gy in 2 fractions) provided effective pain relief, with 12.5% achieving complete response and 37.5% showing partial response.

The treatment was safe, with no cases of spinal cord compression and only one patient requiring surgery for a pathologic fracture, indicating that this approach can be a viable option for patients with poor performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy for complicated bone metastases in patients with poor performance status: a phase II international trial. Silva, MF., Marta, GN., Lisboa, FPC., et al.[2022]

Hypofractionated radiation therapy, which delivers higher doses in fewer sessions, shows promise for treating various cancers, but it poses risks of damaging late-responding normal tissues due to their sensitivity to larger doses.

The long-term safety of hypofractionation depends on factors like the treatment area, total dose, and the patient's baseline health, highlighting the need for careful patient selection and ongoing research to monitor outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Some cases of severe normal tissue toxicity can be anticipated with ablated fractionated radiation with appropriate long-term follow-up. Dolinsky, C., Glatstein, E.[2018]

In a study involving 457 men with localized prostate cancer, hypofractionated high-dose radiotherapy (60 Gy and 57 Gy) was found to be as well tolerated as conventional radiotherapy (74 Gy) over a median follow-up of 50.5 months, with low rates of grade 2 or worse bowel and bladder toxicities.

The rates of bowel toxicity were 4.3% for the conventional group, 3.6% for the 60 Gy group, and 1.4% for the 57 Gy group, indicating that hypofractionated treatment may not increase the risk of side effects compared to standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHiP randomised controlled trial. Dearnaley, D., Syndikus, I., Sumo, G., et al.[2023]

In a study of 39 breast cancer patients treated with an accelerated hypofractionated radiotherapy schedule, no significant lung toxicity or adverse effects were observed after a median follow-up of 43 months, indicating the treatment's safety.

The radiotherapy regimen (34 Gy in 10 fractions plus an 8 Gy boost) was well-tolerated, with only minor skin changes noted in a few patients, suggesting it is a feasible option for adjuvant treatment without significant long-term side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated hypofractionated radiotherapy as adjuvant regimen after conserving surgery for early breast cancer: interim report of toxicity after a minimum follow up of 3 years. Pinnarò, P., Soriani, A., Landoni, V., et al.[2021]

Recent evidence suggests that hypofractionated radiotherapy for prostate cancer is both safe and effective, particularly with a recommended regimen of 60 Gy in 20 fractions, which showed no significant increase in late toxicity.

While moderate hypofractionation has demonstrated positive 5-year outcomes in large trials, further research is needed for extreme hypofractionation techniques, and their use should currently be restricted to clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionation for prostate cancer: an update. Tiberi, D., Vavassis, P., Nguyen, D., et al.[2019]

In a study involving 396 patients treated with ultra-hypofractionated breast radiotherapy, the five-year local-relapse free survival (LRFS) rate was an impressive 98.8%, indicating high efficacy in controlling breast cancer.

While ultra-hypofractionated radiotherapy showed excellent tumor control, certain regimens, particularly the 5.7 Gy weekly fraction and tumor bed boost, were linked to a higher risk of acute and late skin toxicities, highlighting the need for careful treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large scale experience of two ultrahypofractionated 5 fractions regimes after breast conserving surgery from a single centre. Sauvage, LM., Loap, P., Vu-Bezin, J., et al.[2023]

Hypofractionation, which involves delivering larger doses of radiation in fewer sessions, was initially developed to reduce patient burden and save treatment time, but studies have shown that it can lead to more severe late side effects, particularly when doses exceed 2 Gy per fraction.

Research from the University of Texas M.D. Anderson Cancer Center indicates that while hypofractionation may be convenient, it should be approached with caution due to the increased risk of long-term complications, and any use should be justified by specific tumor characteristics and adjusted total doses to minimize morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionation: lessons from complications. Fletcher, GH.[2022]

Hypofractionation in radiotherapy for breast cancer has a strong empirical foundation, showing that shorter treatment schedules can be effective.

Clinical trials have successfully established new standards of care, reducing treatment from 50 Gy in 25 fractions over 5 weeks to as low as 26 Gy in 5 fractions over just 1 week, making treatment more efficient for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From 25 Fractions to Five: How Hypofractionation has Revolutionised Adjuvant Breast Radiotherapy. Yarnold, JR., Brunt, AM., Chatterjee, S., et al.[2022]

Hypofractionated radiation therapy, which delivers fewer but larger doses of radiation over a shorter period, has shown comparable outcomes to conventional radiation in treating breast cancer, suggesting it could be an effective alternative.

Ongoing phase 3 trials are investigating hypofractionated whole breast irradiation and accelerated partial breast irradiation, which may lead to broader acceptance of these methods for early-stage breast cancer, although concerns about patient selection and late toxicity remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiation therapy in the treatment of early-stage breast cancer. Freedman, GM.[2021]

Radiation therapy (RT) as part of breast-conserving treatment or post-mastectomy significantly reduces the risk of local-regional recurrence and improves long-term survival, with most studies using daily doses of 1.8-2 Gray (Gy).

Recent studies on hypofractionated RT schedules, which deliver equivalent doses in a shorter time, have shown similar effectiveness in preventing recurrence and survival rates, with no significant increase in acute or long-term toxicities, although further research is needed to identify suitable patient groups for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abbreviated course of radiotherapy (RT) for breast cancer. Schoenfeld, JD., Harris, JR.[2018]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Accelerated fractionation with a concurrent boost for early stage breast cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Treatment of Breast and Prostate Cancer by Hypofractionated Radiotherapy: Potential Risks and Benefits. [2019]

3. Greece pubmed.ncbi.nlm.nih.gov

Ten Daily Fractions for Whole Breast Cancer Irradiation: Long Term Results. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Outcomes of accelerated hypofractionated radiotherapy in stage i non-small-cell lung cancer. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy for complicated bone metastases in patients with poor performance status: a phase II international trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Some cases of severe normal tissue toxicity can be anticipated with ablated fractionated radiation with appropriate long-term follow-up. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHiP randomised controlled trial. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Accelerated hypofractionated radiotherapy as adjuvant regimen after conserving surgery for early breast cancer: interim report of toxicity after a minimum follow up of 3 years. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Hypofractionation for prostate cancer: an update. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Large scale experience of two ultrahypofractionated 5 fractions regimes after breast conserving surgery from a single centre. [2023]

11. Ireland pubmed.ncbi.nlm.nih.gov

Hypofractionation: lessons from complications. [2022]

12. England pubmed.ncbi.nlm.nih.gov

From 25 Fractions to Five: How Hypofractionation has Revolutionised Adjuvant Breast Radiotherapy. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Hypofractionated radiation therapy in the treatment of early-stage breast cancer. [2021]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Abbreviated course of radiotherapy (RT) for breast cancer. [2018]