High Dose Re-Irradiation for Cancer

(REDIRICT Trial)

Overseen By Sara Herr

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Disqualifiers: Severe conditions, Life expectancy, ECOG 3, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how to safely administer another round of radiation to individuals with solid tumors, focusing on its effects on nearby critical structures such as blood vessels, nerves, and the spinal cord. The trial aims to determine the best approach to manage re-irradiation (repeat radiation therapy) for tumor control while assessing any side effects. It targets individuals whose cancer has returned and overlaps with areas previously treated with radiation. Those with a solid tumor confirmed by biopsy, who require high-dose radiation again, and have undergone prior radiation may be suitable candidates for this trial. As an unphased trial, this study 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. However, it does mention that documentation is required if concurrent cancer therapy drugs are recommended, so it's best to discuss your specific medications with the trial team.

What prior data suggests that re-irradiation therapy is safe for cancer patients?

Research has shown that re-irradiation, or giving radiation treatment a second time, can be safe for patients. In a recent study, patients received nearly twice the initial radiation amount and tolerated it well, experiencing no severe side effects. Another study focused on patients with spine problems who underwent re-irradiation. The results indicated that this treatment was often successful and did not cause serious issues. Overall, these findings suggest that re-irradiation can be a safe option for treating cancer, even in previously treated areas. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about high dose re-irradiation for cancer because it allows for the treatment of tumors that overlap with previously irradiated areas. Unlike standard radiation therapy, which typically avoids re-irradiating the same area due to risks to nearby organs, this approach carefully targets the tumor while minimizing damage to healthy tissue. This technique opens up new possibilities for treating recurrent or persistent tumors that might not respond to conventional methods. By pushing the boundaries of radiation therapy, this approach could improve outcomes for patients with challenging cancer cases.

What evidence suggests that re-irradiation might be an effective treatment for cancer?

Research has shown that re-irradiation, or giving radiation therapy again, can help treat cancer in patients who have already received radiation. In this trial, participants will receive high-dose re-irradiation to treatment volumes overlapping previously irradiated areas. One study found that re-irradiation increased the chance of living for two more years from 11% to 32% and improved the time patients lived without their cancer worsening from 7% to 31%. Another study on spine treatments showed that 61% of patients were alive after one year, and only 12% experienced cancer recurrence in the treated area. These findings suggest that re-irradiation can significantly aid survival and cancer control for patients needing additional radiation treatment. ^{2 3 4 6 7}

Who Is on the Research Team?

Elizabeth M. Gore

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

Adults (18+) with stage I-IV solid tumors previously treated with radiation, now needing high dose re-irradiation. Must have a life expectancy of at least 6 months, an ECOG score of 0-2 indicating they are able to perform daily activities, and acceptable organ function as shown by specific lab values. Pregnant women or those not using contraception are excluded.

Inclusion Criteria

Provision of signed informed consent

Baseline labs are per standard practice. Values will be dependent on the OARs being treated. Recommended labs and values include: Aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5 x upper limit of normal (ULN) or < 5 x ULN with metastatic liver disease, Total bilirubin < 1.5 x ULN, Absolute neutrophil count (ANC) > 500 cells/mm^3, Platelets > 50,000 cells/mm^3, Creatinine < 1.5 x ULN or Creatinine clearance > 45 mL/min if creatinine is > 1.5 x ULN (calculated Creatinine Clearance (CrCl) based on Cockcroft-Gault equation), Eastern Cooperative Oncology Group (ECOG) Performance Score 0-2, Patients must have resolution of acute toxic effect(s) of most recent cancer therapy to Grade 1 or 2, Life expectancy of at least 6 months, Female patients of childbearing potential must have negative urine or serum pregnancy test within 7 days prior to start of re-irradiation, Ability to complete the self-reported questionnaires (translations will be made available if the patient's primary language is not English), Concurrent participation on pharmaceutical, investigator-initiated, National Clinical Trials Network (NCTN), or other multisite clinical trials that include re-irradiation is allowed

My cancer was surgically removed from an area previously treated with radiation, and I'm at high risk of it coming back.

Exclusion Criteria

I need help with my daily activities due to my health condition.

Life expectancy of less than 6 months

Women of childbearing potential who are known to be pregnant or are unwilling to use an acceptable method of contraception from the time of informed consent until completion of the course of radiotherapy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Re-Irradiation Treatment

Participants receive high-dose re-irradiation therapy targeting previously irradiated organs at risk

Varies per patient

Follow-up

Participants are monitored for organ-specific grade 3-5 toxicities and tumor control

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Re-irradiation

Trial Overview The trial is testing a standardized approach for re-irradiating patients who have had prior radiation therapy. It focuses on advanced imaging techniques for planning treatment and monitoring the effects on organs at risk (like arteries, nerves, spinal cord) over time.

How Is the Trial Designed?

Group I: Cancer patients receiving definitive radiation therapy with overlap of a previously treated field Experimental Treatment 1 Intervention

This is a re-irradiation study in solid tumor patients receiving definitive high dose radiation therapy to treatment volumes that include overlap with previously irradiated organs at risk.

Re-irradiation is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Re-irradiation for:

• Recurrent cancer
• Metastatic cancer
• Local recurrences

Approved in United States as Re-irradiation for:

• Breast cancer recurrences
• Head and neck cancer recurrences
• Lung cancer recurrences
• Prostate cancer recurrences

Approved in Canada as Re-irradiation for:

• Recurrent malignancies
• Metastatic disease

Approved in Japan as Re-irradiation for:

• Recurrent tumors
• Locoregional recurrences

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

Long-term cancer survivors may require re-irradiation due to recurrence or new primary cancers, and studies indicate that certain normal tissues can tolerate significant doses of retreatment radiation.

To minimize the risk of normal tissue damage and improve quality of life, re-irradiation should be performed with precision, using techniques like hyperfractionation or highly conformal stereotactic approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Principles and Practice of Re-irradiation in Clinical Oncology: An Overview. Dörr, W., Gabryś, D.[2019]

Re-irradiation can be a valuable option for patients with cancer experiencing local recurrence or new tumors near previously treated areas, especially as new radiotherapy techniques improve treatment precision.

A consensus document, supported by major European oncology organizations, aims to standardize re-irradiation practices and classifications, which will enhance clinical decision-making and facilitate future research on its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus on re-irradiation: definition, reporting, and clinical decision making. Andratschke, N., Willmann, J., Appelt, AL., et al.[2022]

Reirradiation can be a necessary option for palliation in patients, but it carries risks of exceeding normal tissue tolerances, which can lead to increased toxicity.

The article reviews existing literature on reirradiation to provide clinicians with important information about its efficacy, potential benefits, and side effects, helping them make informed treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with retreatment for palliation. Morris, DE.[2019]

In a study of 26 patients with recurrent esophageal cancer, re-irradiation using a hyperfractionated technique showed a median overall survival of 15.8 months, with 1-year and 3-year survival rates of 64.3% and 28.3%, respectively, indicating promising efficacy.

The study found that higher doses of re-irradiation and concurrent chemotherapy significantly improved survival rates, while the incidence of severe late adverse effects was relatively low, with only 19.2% of patients experiencing grade 3 or higher complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperfractionated radiotherapy for re-irradiation of recurrent esophageal cancer. Takeda, K., Matsushita, H., Umezawa, R., et al.[2022]

In a study of 25 women undergoing reirradiation for recurrent or second primary pelvic cancers, 56% achieved cancer-free status after treatment, with follow-up periods ranging from 10 to 61 months.

However, 50% of the patients experienced major complications, with three requiring surgical intervention, highlighting the need for careful patient selection and consideration of risks associated with reirradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radical reirradiation for recurrent or second primary carcinoma of the female reproductive tract. Russell, AH., Koh, WJ., Markette, K., et al.[2019]

A second re-irradiation treatment, with cumulative doses exceeding 90 Gy, can provide significant palliative benefits for patients with incurable cancer, as demonstrated in cases of sacral bone metastases and recurrent rectal cancer.

Patients experienced symptomatic relief without clinically relevant side effects, suggesting that re-irradiation can be a safe option for extending quality of life in those who previously tolerated radiation well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second Re-irradiation: Clinical Examples of Worthwhile Treatment. Nieder, C., Yobuta, R., Mannsåker, B.[2020]

In a study of 42 patients with recurrent breast cancer, repeat radiotherapy combined with hyperthermia was found to be feasible and resulted in acceptable levels of late toxicity, with no higher graded late toxicity observed after a median follow-up of 41 months.

The treatment achieved a 5-year local control rate of 62% and an overall survival rate of 59%, indicating that repeat radiotherapy can improve prognosis, especially for patients who had previous tumor resections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Re-surgery and chest wall re-irradiation for recurrent breast cancer: a second curative approach. Müller, AC., Eckert, F., Heinrich, V., et al.[2021]

Re-irradiation is becoming more common as patients live longer with cancer, but it requires careful patient selection and consideration of factors like performance status and disease-free intervals to minimize risks.

The review highlights the importance of understanding radiobiological factors and tissue recovery to guide clinicians in making informed decisions about re-irradiation, balancing potential benefits against the risk of toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complex Clinical Decision-Making Process of Re-Irradiation. Armstrong, S., Hoskin, P.[2021]

In a study of 52 patients undergoing re-irradiation for spine or pelvic bone metastases, the majority experienced only mild adverse events, with most being below grade 2 severity.

The study found that re-irradiation was generally safe, as no severe late adverse events (grade 3 or worse) were reported, indicating that this treatment can be considered within acceptable safety limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and severity of adverse events associated with re-irradiation for spine or pelvic bone metastases. Hirano, Y., Nakamura, N., Zenda, S., et al.[2018]

Reirradiation can be beneficial for patients with recurrent nasopharynx cancer and glioma, potentially improving local control and progression-free survival, based on a systematic review of 7 recent trials involving a median of 60 patients.

Hyperfractionated radiotherapy has emerged as the preferred method for treating recurrent, inoperable nasopharynx cancer, although there are concerns about serious toxicity from high cumulative doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective randomized clinical studies involving reirradiation: update of a systematic review. Nieder, C., Willmann, J., Andratschke, NH.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1879850025002206

Long-Term Outcomes After Reirradiation With Spine ... At 1 year, overall survival was 61% with a cumulative incidence of local failure at 12% and vertebral compression fracture at 9% considering ...

2. consultqd.clevelandclinic.org consultqd.clevelandclinic.org/understanding-the-role-of-re-irradiation

Understanding the Role of Re-irradiation - Consult QD Re-irradiation of solid tumors​​ For example, patients with head and neck cancers often receive 70 units of radiation for five to seven weeks at ...

3. advancesradonc.com advancesradonc.com/article/S2452-1094(17)30036-2/fulltext

Preserving the legacy of reirradiation: A narrative review ... Seven patients (11%) died during treatment or within the first month. Unsatisfactory outcome was seen in patients with oral cavity and hypopharynx tumors. These ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4690995/

Outcomes of reirradiation in the treatment of patients with ... The median overall survival for all patients after diagnosis of metastases was 24.7 months, after the re-irradiation WBRT (re-WBRT) it was 5.3 months (95% CI, ...

5. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)00200-7/fulltext

Re-irradiation versus systemic therapy for the management ... Re-irradiation improved 2-year overall survival, (32 % versus 11 %), progression-free survival (31 % versus 7 %), and local–regional control (39 % versus 3 %) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5514242/

Preserving the legacy of reirradiation: A narrative review of ... The purpose of this study is to illustrate the historical development of reirradiation during several decades of the 20th century, in particular between 1920 ...

7. ar.iiarjournals.org ar.iiarjournals.org/content/30/9/3781

Re-irradiation of Head and Neck Cancer–Impact of Total ... Higher overall doses of re-irradiation gave a statistically significant better outcome with regard to overall survival (p=0.018). Conclusion: For patients with ...