Hypofractionated Radiotherapy for Cancer

(RT-PACE Trial)

Overseen By Rachel Kingsford

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: University of Utah

Disqualifiers: Prior irradiation, Inflammatory bowel disease, Recent malignancy, 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: 1

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether hypofractionated radiotherapy, a special type of radiation, can effectively treat cervical or endometrial cancer. The approach involves delivering higher doses of radiation over a shorter period, potentially killing more tumor cells while causing fewer side effects. This study may suit individuals who have had a hysterectomy due to cervical or endometrial cancer and do not have metastatic disease. As an unphased trial, it offers a unique opportunity to contribute to innovative research that could enhance future cancer treatments.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It mentions that chemotherapy can be administered at the discretion of your oncologist, so it's best to discuss your specific medications with your doctor.

What prior data suggests that hypofractionated radiotherapy is safe for treating cervical or endometrial cancer?

Research has shown that hypofractionated radiation therapy is generally easy for patients to handle. In one study involving 9,074 men across 13 clinical trials, no significant difference appeared in the time without cancer returning between those who received hypofractionated radiation and those who underwent conventional radiation. This indicates that the treatment does not lead to worse outcomes. Another study found that a similar type of therapy caused few side effects, with more than half of breast cancer patients experiencing no skin problems.

For breast cancer patients, ultra-hypofractionated therapy resulted in low rates of immediate side effects, meaning patients experienced few short-term issues. These findings suggest that hypofractionated radiation therapy is safe and may have fewer side effects compared to traditional methods. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Hypofractionated radiation therapy is unique because it delivers higher doses of radiation over a shorter period, typically just three weeks, compared to the five to seven weeks required for conventional radiation therapy. This approach can potentially reduce the overall treatment time for patients without compromising effectiveness. Researchers are excited about this treatment because it could lead to fewer hospital visits and a more convenient treatment schedule, improving the quality of life for patients while still effectively managing cancer. Additionally, by minimizing the duration of therapy, there is hope for reduced healthcare costs and resource utilization.

What evidence suggests that hypofractionated radiotherapy is effective for cervical or endometrial cancer?

Research has shown that hypofractionated radiation therapy (HFRT) can be as effective as traditional radiation for certain cancers. Studies involving thousands of participants have demonstrated that HFRT achieves similar success rates in maintaining cancer-free status compared to conventional methods. HFRT may also result in fewer side effects and is particularly beneficial for tumors that respond well to higher doses of radiation over a shorter period. For cancers such as cervical or endometrial, this treatment could be a promising option. Participants in this trial will receive HFRT over three weeks, provided there is no disease progression or unacceptable toxicity. ^{1 4 6 7 8}

Who Is on the Research Team?

Gita Suneja

Principal Investigator

Huntsman Cancer Institute/ University of Utah

Are You a Good Fit for This Trial?

This trial is for adults over 18 with cervical or endometrial cancer, who've had a hysterectomy and are in good health post previous cancer treatments. They must be able to consent, have an ECOG status of <=2, non-metastatic disease, and a life expectancy over 2 years. Those with recent other cancers or certain medical conditions can't join.

Inclusion Criteria

My doctor decides if I need chemotherapy along with radiation.

I had a hysterectomy for cervical or endometrial cancer.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

It's been over 16 weeks since my hysterectomy, but I had chemotherapy before starting radiotherapy.

I haven't been diagnosed with any cancer other than skin, breast, bladder, or cervical cancers in the last 2 years.

Medical, psychiatric, cognitive, or other conditions in the opinion of the investigator that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo hypo-fractionated radiotherapy over 3 weeks in the absence of disease progression or unacceptable toxicity

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Follow-up at 1, 3, and 6 months and then at 1, 2, and 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Hypofractionated Radiation Therapy

Trial Overview The study tests hypo-fractionated radiotherapy for cervical/endometrial cancer treatment. This method uses higher radiation doses given in a shorter time frame than traditional therapy, aiming to kill more tumor cells while reducing side effects.

How Is the Trial Designed?

Group I: Treatment (hypo-fractionated radiotherapy) Experimental Treatment 1 Intervention

Patients undergo hypo-fractionated radiotherapy over 3 weeks in the absence of disease progression or unacceptable toxicity.

Hypofractionated Radiation Therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Approved in European Union as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Approved in Canada as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Hypofractionated radiation therapy (HFRT) demonstrated a freedom from local progression (FFLP) rate of 79.8% at 1 year and 67.8% at 2 years in 64 patients with non-small cell lung cancer who were unfit for surgery or stereotactic body radiation therapy, indicating its efficacy in this patient population.

The treatment showed acceptable safety, with only 6.3% of patients experiencing severe pulmonary toxicities, suggesting that HFRT can be a viable option for patients who cannot undergo more aggressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of 10-fraction hypofractionated radiation therapy for non-small cell lung cancer. Yoo, YJ., Kim, SS., Song, SY., et al.[2021]

In a study of 56 breast cancer patients receiving hypofractionated external beam radiotherapy (HFRT) after mastectomy, the treatment was well tolerated with mild to moderate acute skin toxicity, and no severe hematological toxicity was observed, indicating a favorable safety profile.

HFRT effectively delivered targeted doses to the chest wall while minimizing exposure to surrounding organs, with mean lung and heart doses remaining within safe limits, suggesting that HFRT can be a viable option for post-mastectomy radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Study on Dosimetric Outcomes and Acute Toxicity of Post Mastectomy Adjuvant Hypofractionated Radiotherapy for Breast Cancer. Deshmukh, S., Sharan, K., Fernandes, DJ., et al.[2022]

In a study of 274 early breast cancer patients treated with hypofractionated radiation treatment (HFRT) over a median follow-up of 7 years, the local recurrence-free survival rate was very high at 97.2%, indicating that HFRT is effective in preventing local cancer recurrence.

The acute toxicity associated with HFRT was generally low, with most patients experiencing less than grade 3 side effects, suggesting that HFRT is a safe treatment option for eligible patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiation treatment in early breast cancer: Results in a New Zealand setting. James, ML., Dehn, G., Robinson, BA.[2018]

In a study involving 160 prostate cancer patients, both hypofractionated radiation therapy regimens (56 Gy in 16 fractions and 67 Gy in 25 fractions) were found to be safe, with manageable levels of acute gastrointestinal and urinary toxicity.

Acute grade ≥2 gastrointestinal toxicity occurred in 26% of patients in the 56 Gy group and 20% in the 67 Gy group, indicating that both treatment schedules are effective options with acceptable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

4 Weeks Versus 5 Weeks of Hypofractionated High-dose Radiation Therapy as Primary Therapy for Prostate Cancer: Interim Safety Analysis of a Randomized Phase 3 Trial. Fonteyne, V., Sarrazyn, C., Swimberghe, M., 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]

In a study of 463 breast cancer patients, hypofractionated radiotherapy (HFRT) showed a similar rate of locoregional recurrence compared to conventional fractionated radiotherapy (CFRT), with 2.7% recurrence in HFRT versus 4.3% in CFRT.

The 4-year local recurrence-free survival rates were also comparable, with 97% for HFRT and 95% for CFRT, indicating that HFRT is a safe and effective alternative for treating locally advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative retrospective analysis of locoregional recurrence in unselected breast cancer patients treated with conventional versus hypofractionated radiotherapy at a tertiary cancer center? Yadav, R., Lal, P., Agarwal, S., et al.[2022]

In a study of 81 patients with localized breast cancer treated with hypofractionated radiotherapy (HFRT), the treatment was well-tolerated, with low rates of late toxicities such as chest pain (11%) and limb pain (12%).

The five-year overall survival rate was 76.5%, and there were no locoregional recurrences, indicating that HFRT is effective in controlling the disease while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of toxicities and outcomes in patients with breast cancer treated with hypofractionated radiotherapy. Sindhu, M., Malik, M., Ahmed, SF., et al.[2022]

High-dose, hypofractionated radiotherapy (HFRT) demonstrated a high overall response rate of 79% and a one-year local-progression free rate of 50% in treating head-and-neck malignancies, based on a retrospective analysis of 48 patients.

The study found that delivering doses of 6Gray or higher per fraction improved locoregional control, and increased toxicity was not observed with doses of 8Gray or more, suggesting that HFRT can be both effective and safe for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose hypofractionated radiotherapy is effective and safe for tumors in the head-and-neck. Teckie, S., Lok, BH., Rao, S., et al.[2022]

In a study of 1,010 breast cancer patients, hypofractionated radiotherapy (HFRT) showed similar locoregional recurrence-free survival (LRRFS) and disease-free survival (DFS) rates compared to conventionally fractionated radiotherapy (CFRT) after a median follow-up of 49.5 months.

While HFRT was effective across various nodal stages and molecular subtypes, it tended to show lower DFS in N2-3 patients with triple-negative breast cancer compared to CFRT, indicating a need for further investigation in this specific group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Practice of Hypofractionated Radiotherapy in Patients With Invasive Breast Cancer. Chen, F., Hui, TSK., Ma, L., et al.[2022]

Hypofractionated radiation therapy (HFRT) at a dose of 52.5 Gy over 15 fractions was found to be feasible and effective for selected elderly patients with newly diagnosed glioblastoma, showing a median overall survival of 8 months and a 12-month overall survival rate of 30%.

The study indicated that HFRT resulted in limited toxicity, with no increase in steroid use during treatment, and some patients even experienced a reduction in steroid requirements, suggesting a favorable safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of hypofractionated radiation therapy in elderly patients with newly diagnosed glioblastoma with poor prognosis. Navarria, P., Pessina, F., Cozzi, L., et al.[2019]

Hypofractionated radiation therapy (HypoRT) was found to be effective in treating inoperable advanced non-small cell lung cancer (NSCLC), with an overall response rate of 83% among 30 patients, and a median follow-up of 13 months.

The treatment was well-tolerated, with manageable acute toxicities; however, 37% of patients experienced locoregional recurrence, and 57% developed distant metastasis, indicating the need for further studies to compare HypoRT with conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer. Osti, MF., Agolli, L., Valeriani, M., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10845660/

Efficacy and safety analysis of hypofractionated and ... In this meta-analysis, we conducted a comparative analysis of the safety and efficacy of hypofractionated and conventional fractionated ...

2. ascopubs.org ascopubs.org/doi/10.1200/GO-24-00277

Phase II Evaluation of Ultra-Hypofractionated ... The study found that ultra-hypofractionated radiation therapy in patients with breast cancer had low rates of acute toxicity and cosmesis changes.

3. e-roj.org e-roj.org/journal/view.php?year=2024&vol=42&spage=171

Part 3. Genitourinary and gynecological cancers Furthermore, hypofractionated RT is potentially more beneficial for tumors with a low α/β ratio compared with conventional fractionation RT.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12548115/

evidence from 9074 men in 13 randomized clinical trials There was no statistically significant difference in relapse-free survival after five years of treatment between the HFRT and CFRT groups. In ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa0906260

Long-Term Results of Hypofractionated Radiation Therapy ... At 10 years, the probability of survival was 84.4% in the control group as compared with 84.6% in the hypofractionated-radiation group (absolute difference, − ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1526820925002344

Real World Safety of Adjuvant Ultra Hypofractionated ... Ultra-hypofractionated breast radiotherapy (26 Gy in 5 fractions) was well tolerated. · More than half of patients showed no skin toxicity; grade ...

7. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-024-11918-2

Efficacy and safety analysis of hypofractionated ... - BMC Cancer In this meta-analysis, we conducted a comparative analysis of the safety and efficacy of hypofractionated and conventional fractionated ...

8. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00034-8/abstract

Hypofractionated radiotherapy for prostate cancer (HYDRA) Hypofractionated radiotherapy for prostate cancer (HYDRA): an individual patient data meta-analysis of randomised trials in the MARCAP consortium.