High Dose Re-Irradiation for Cancer

(REDIRICT Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Elizabeth M. Gore

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Medical College of Wisconsin

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

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial applies a uniform approach to re-irradiation for planning and diagnostic image fusion, dose summation, dose calculations, and follow up for tumor control and detailed toxicity analysis of serial Organs At Risk (OARs). Serial organs include named arteries and nerves, spinal cord, and gastrointestinal tract.

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 data supports the effectiveness of the treatment High Dose Re-Irradiation for Cancer?

Re-irradiation can help control cancer that comes back or appears near a previously treated area, especially when other treatment options are limited. New techniques in radiotherapy have improved the ability to target these areas more precisely, which can make re-irradiation a more viable option for some patients. ^{1 2 3 4 5}

Is high dose re-irradiation generally safe for humans?

Re-irradiation can be safe for humans, but it carries risks of severe side effects, especially in tissues that have already been exposed to radiation. Studies suggest that while some normal tissues can handle a second round of radiation, there is a significant risk of complications, and treatments should be done with great care to minimize damage. ^{5 6 7 8 9}

How is re-irradiation treatment different from other cancer treatments?

Re-irradiation treatment is unique because it involves giving a second round of radiation to a previously treated area, which requires careful planning to avoid damaging normal tissues. It is used when cancer recurs or a new cancer develops in the same area, and it often involves advanced techniques to precisely target the tumor while minimizing exposure to healthy tissue. ^{1 3 4 5 10}

Research Team

Elizabeth M. Gore

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Re-irradiation (Radiation Therapy)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Dr. Joseph E. Kerschner

Medical College of Wisconsin

Chief Medical Officer since 2011

MD, specific institution not identified

Dr. John R. Raymond, Sr.

Medical College of Wisconsin

Chief Executive Officer since 2010

MD from the Medical University of South Carolina

Findings from Research

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]

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]

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]

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]

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 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 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 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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Prospective randomized clinical studies involving reirradiation: update of a systematic review. [2023]

2. England 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. [2022]

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

Second Re-irradiation: Clinical Examples of Worthwhile Treatment. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Re-surgery and chest wall re-irradiation for recurrent breast cancer: a second curative approach. [2021]

5. England pubmed.ncbi.nlm.nih.gov

The Principles and Practice of Re-irradiation in Clinical Oncology: An Overview. [2019]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Hyperfractionated radiotherapy for re-irradiation of recurrent esophageal cancer. [2022]

7. Japan pubmed.ncbi.nlm.nih.gov

Incidence and severity of adverse events associated with re-irradiation for spine or pelvic bone metastases. [2018]

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

Clinical experience with retreatment for palliation. [2019]

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

Radical reirradiation for recurrent or second primary carcinoma of the female reproductive tract. [2019]

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

Complex Clinical Decision-Making Process of Re-Irradiation. [2021]