Hypofractionated Radiotherapy vs Single Fraction Radiosurgery for Brain Metastasis Patients on Immunotherapy (HYPOGRYPHE)

Plain English Summary

Comparing Single vs Multiple Dose Radiation for Cancer Patients With Brain Metastasis and Receiving Immunotherapy is a Not Applicable clinical trial sponsored by Wake Forest University Health Sciences studying NSCLC, Renal Cell Carcinoma, Breast Carcinoma, Melanoma, Brain Metastases, Adult, Non-small Cell Lung Cancer, SCLC, Small-cell Lung Cancer. This trial compares two ways of giving radiation therapy to brain tumors: a single high dose versus a lower dose given over a few days. It is for adults with certain types of cancer (lung, breast, kidney, melanoma) that have spread to the brain and who are receiving immunotherapy. Participation involves receiving one of the two radiation treatments and regular check-ups. The alternative is the standard single-dose radiation treatment (SSRS). The trial aims to enroll 58 participants.

Official Summary

This study is designed to see if we can lower the chance of side effects from radiation in patients with breast, kidney, small cell lung cancer, non-small cell lung cancer or melanoma that has spread to the brain and who are also being treated with immunotherapy, specifically immune checkpoint inhibitor (ICI) therapy. This study will compare the usual care treatment of single fraction stereotactic radiosurgery (SSRS) given on one day versus fractionated stereotactic radiosurgery (FSRS), which is a lower dose of radiation given over a few days to determine if FSRS is better or worse at reducing side effects than usual care treatment.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with one or more brain tumors (metastases) up to 15 in number and a total tumor volume of 30 cc or less. Patients must have specific types of cancer (melanoma, kidney, non-small cell lung, small cell lung, or breast cancer) that have spread to the brain. Individuals must be receiving or planning to receive immunotherapy (immune checkpoint inhibitors) within 30 days of radiation. People with certain brain conditions like leptomeningeal carcinomatosis or those who have had whole-brain radiation are not eligible. This trial is studying NSCLC, Renal Cell Carcinoma, Breast Carcinoma, Melanoma, Brain Metastases, Adult, Non-small Cell Lung Cancer, SCLC, Small-cell Lung Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The main goal is to see if the lower, spread-out radiation dose causes fewer serious side effects (like swelling or damage) to the brain within 9 months compared to the single high dose. The specific primary outcome measures are: Occurrence of a Grade 2 or higher Adverse Radiation Effect (ARE) (9 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This study does not have a traditional clinical phase designation. It may be an observational study that follows patients without intervening in their care, an expanded access or compassionate use program, or other non-interventional research. These studies contribute valuable data about disease progression, treatment patterns, and patient outcomes.

Why This Trial Matters

This trial aims to find a radiation approach that reduces side effects for cancer patients with brain metastases who are also on immunotherapy, addressing a need for gentler treatment options. This research targets NSCLC, Renal Cell Carcinoma, Breast Carcinoma, Melanoma, Brain Metastases, Adult, Non-small Cell Lung Cancer, SCLC, Small-cell Lung Cancer, where improved treatment options are needed.

Investor Insight

This trial focuses on a growing patient population with brain metastases on immunotherapy, a market segment where optimizing treatment to minimize toxicity is crucial for patient quality of life and p

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of both single-dose and multi-dose radiation for your specific situation. Understand that you will be randomly assigned to one of the two treatment groups. Day-to-day involvement includes attending radiation appointments and follow-up visits for monitoring. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 58 participants

Interventions

• RADIATION: single fraction stereotactic radiosurgery (SSRS) — SSRS is an advanced radiation technique that delivers high dose precision radiation in a single dose to discrete intracranial lesions.
• RADIATION: fractionated stereotactic radiosurgery (FSRS) — FSRS is an advanced radiation technique that uses a lower dose precision radiation delivered over 3 to 5 treatments given daily or every other day to intracranial lesions.

Primary Outcomes

• Occurrence of a Grade 2 or higher Adverse Radiation Effect (ARE) (9 months)

Secondary Outcomes

• Compare time to composite end point (9 months)
• Compare time to local failure between SSRS and FSRS groups (9 months)
• Compare time to neurologic death between groups (9 months)
• Compare patient-reported brain tumor specific symptom burden (9 months)

Full Eligibility Criteria

Inclusion Criteria:

* At least one intact brain metastasis or resection cavity ≥ 2 cm in diameter or ≥ 4 cc volume.

  * Patients at initial diagnosis of brain metastases and patients with known brain metastasis treated with systemic therapy alone are eligible.
  * Patients who have previously undergone SRS for brain metastases are eligible if all MRIs and DICOM-RT files from prior SRS courses are available for upload to TRIAD and there are no lesions requiring re-irradiation. Prior SRS data upload is NOT required prior to enrollment and randomization. Both SSRS and FSRS are acceptable.
  * Lesion volume will be approximated by measuring the lesion's three perpendicular diameters on contrast-enhanced, T1-weighted MRI and the product of those diameters will be divided by 2 to estimate the lesion volume (e.g., xyz/2). Alternatively, direct volumetric measurements via slice-by-slice contouring on a treatment planning software package can be used to calculate the total tumor volume.
  * Any extent of non-CNS disease is allowed. There is no requirement for non-CNS disease to be controlled prior to study entry.
  * For patients considered to be borderline or potentially eligible by size or volume criteria, sites have the option to send in DICOM films for central review screening.
* Age ≥ 18 years at the time of enrollment.
* Total number of brain metastases (including resection cavities) ≤ 15 on diagnostic MRI; all lesions must be amenable to SSRS and FSRS as determined by the treating radiation oncologist. Treatment must take place at a facility credentialed by the Imaging and Radiation Oncology Core (IROC) for SRS and that offers both SSRS and FSRS as treatment options.
* Total gross tumor volume must be ≤ 30 cc. Lesion volume will be approximated by measuring each lesion's three perpendicular diameters on contrast-enhanced T1 MRI and the product of those diameters will be divided by 2 (V = xyz/2). Direct volumetric measurements by contouring all lesions on all visible slices on treatment planning software is also acceptable. If there is a cavity, only gross residual disease within or adjacent to the cavity is counted toward the 30 cc total volume.
* Ability to tolerate MRI brain with gadolinium-based contrast.
* Pathologically confirmed melanoma, renal cell carcinoma, non-small cell lung cancer, small cell lung cancer, or breast cancer.
* Has received, is currently receiving, or is planned to receive immune checkpoint inhibitor therapy (defined as agent targeted to PD-1/PD-L1 axis) within 30 days of the planned first day of SSRS/FSRS. Dual ICI therapy with PD-1/PD-L1 and CTLA-4 targeted agents are allowed, but patients treated with a single agent CTLA-4 targeted agent only are ineligible.

  o It is not mandatory to wait for the results of next generation sequencing (NGS) or other molecular tumor testing to determine if the patient is planned to receive ICI if the enrolling physician feels that identification of a mutation that would preclude ICI therapy (such as an EGFR mutation in a patient with NSCLC) is unlikely to be identified.
* Karnofsky Performance Status (KPS) ≥ 50. Refer to Appendix A.
* Negative serum or urine pregnancy test within 14 days of randomization for women of child-bearing potential.
* Ability to understand and the willingness to sign written informed consent.
* Patients must be able to provide informed consent.
* Must be able to speak, read and understand English or Spanish

Exclusion Criteria:

* Prior fractionated, whole, or partial brain radiation therapy. Prior fractionated SRS is acceptable.
* Prior courses of SRS for benign tumors such as meningiomas, pituitary adenomas, schwannomas may be acceptable if the treatment is \> 2cm away from the site of a metastatic lesion that would be treated on this study. The study PI or a designated co-PI must review this type of case to confirm eligibility prior to enrollment.
* Prior diagnosis ARE, including pseudoprogression or radiation necrosis/radionecrosis, or previously treated lesions being actively evaluated for possible ARE or local failure such as concerning imaging findings currently being tracked with short interval MRI.
* Leptomeningeal carcinomatosis established by lumbar puncture cytology, or MRI imaging. In the absence of a clinical indication, a lumbar puncture is not required to confirm eligibility.
* A brain metastasis that is 5 mm or less from the optic chiasm or optic nerves
* Inability to tolerate brain MRI or receive gadolinium-based contrast
* Planned or prior therapy with bevacizumab (or bevacizumab biosimilar) within 30 days of the planned first day of SRS as part of a systemic therapy regimen at study enrollment.
* Serious intercurrent illness or medical condition judged by the local investigator to compromise the patient's safety, preclude safe administration of the planned protocol treatment, or would not permit the patient to be managed according to the protocol guidelines.

Trial Locations

• Lewis Cancer and Research Pavilion at Saint Joseph's/Candler, Savannah, Georgia, United States
• Decatur Memorial Hospital, Decatur, Illinois, United States
• Crossroads Cancer Center, Effingham, Illinois, United States
• HSHS Saint Elizabeth's Hospital, O'Fallon, Illinois, United States
• OSF Saint Francis Medical Center, Peoria, Illinois, United States
• Trinity Health Saint Joseph Mercy Hospital Ann Arbor, Ann Arbor, Michigan, United States
• Trinity Health IHA Medical Group Hematology Oncology - Brighton, Brighton, Michigan, United States
• Genesys Hurley Cancer Institute, Flint, Michigan, United States
• Trinity Health Saint Mary Mercy Livonia Hospital, Livonia, Michigan, United States
• Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus, Ypsilanti, Michigan, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Non-small Cell Lung Cancer (NSCLC)
• Renal Cell Carcinoma (Kidney Cancer)
• Breast Carcinoma
• Melanoma
• Brain Metastases
• Small Cell Lung Cancer (SCLC)
• Cancer Immunotherapy
• Stereotactic Radiosurgery
• Radiation Oncology
• Neurological Complications of Cancer

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