RAD101 Imaging for Brain Cancer

(RAD101 Trial)

Recruiting at 4 trial locations

Overseen By Dimitris Voliotis, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Radiopharm Theranostics, Ltd

Disqualifiers: Additional malignancy, Brain surgery, Radiation, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging method called RAD101 PET to detect recurrent brain metastases from solid tumors such as lung, breast, or melanoma. The goal is to determine if RAD101 can accurately display these tumors on scans, potentially improving treatment planning. Participants will receive one dose of RAD101 and undergo both PET and MRI scans. Ideal candidates are adults with a history of brain metastases from solid tumors who suspect tumor recurrence but have not yet confirmed it. As a Phase 2 trial, this research measures RAD101's effectiveness in an initial, smaller group, offering a chance to contribute to advancements in cancer detection.

Do I have to stop taking my current medications for the RAD101 Imaging for Brain Cancer trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor to get specific guidance based on your situation.

What prior data suggests that RAD101 imaging is safe for brain cancer patients?

Studies have shown that RAD101 is generally well-tolerated in humans. In a previous study, RAD101 successfully detected brain tumors in all 22 patients without any major safety issues. This suggests that the treatment is safe for humans, although more detailed safety information will emerge as research continues.

Additionally, RAD101 has received Fast Track Designation from the FDA, indicating promise and a reasonable safety profile in early studies. However, since these findings are preliminary, further monitoring is necessary to confirm safety in a larger group. Prospective participants should consult their doctor about potential risks before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

RAD101 is unique because it uses an innovative imaging technique called 18F-Fluorescence Polarization Immunoassay (FPIA) to potentially enhance the detection of brain cancer. Unlike traditional imaging options like MRI or CT scans, this method could offer more precise targeting of cancerous cells by highlighting them with a special fluorescent marker. Researchers are excited about RAD101 because it might allow doctors to see tumors more clearly and earlier, which could lead to better treatment planning and outcomes for patients.

What evidence suggests that RAD101 imaging is effective for detecting brain cancer?

Studies have shown that RAD101 is promising for imaging brain metastases. Research at Imperial College London found that RAD101 effectively targeted brain tumors in both previously treated and untreated patients. In this trial, participants will receive a single dose of RAD101, which focuses on a protein called FASN, enhancing the visibility of brain metastases. This clarity helps distinguish between a returning tumor and radiation-induced tissue damage. RAD101's high accuracy in identifying tumors instills confidence in its performance, suggesting it could improve the diagnosis and management of brain cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Dimitris Voliotis, MD

Principal Investigator

Radiopharm Theranostics

Are You a Good Fit for This Trial?

This trial is for adults over 18 with suspected recurrent brain metastases from solid tumors. Participants must be eligible based on a screening and will receive RAD101 to assess its imaging performance via PET scan, alongside MRI.

Inclusion Criteria

I have advanced cancer (lung, breast, colon, kidney, melanoma) with brain metastases.

Life expectancy ≥4 months

I am not pregnant and follow the required birth control measures.

Exclusion Criteria

I have not had brain surgery in the last 4 weeks.

I have not had brain radiation therapy in the last 6 weeks.

My heart's electrical activity is not normal, or I have a history of long QT syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Imaging and Safety Follow-Up

Participants receive a single dose of RAD101 and undergo PET and MRI imaging, followed by safety assessments

3 days

1 visit (in-person), 1 follow-up call

Data Collection

Longitudinal MRI scans and/or biopsies are collected according to Standard of Care, with data collected for central reading

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RAD101

Trial Overview The study tests the effectiveness of RAD101 (18F-FPIA) in improving PET scan images for detecting recurrent brain metastases. It's an open-label, single-arm trial where participants get one dose of RAD101 followed by brain scans.

How Is the Trial Designed?

Group I: RAD101 (18F-Fluorescence polarization immunoassay (FPIA)) Experimental Treatment 1 Intervention

370 MBq (10 mCi) single dose administered at Day 1 visit

Who Is Running the Clinical Trial?

Radiopharm Theranostics, Ltd

Lead Sponsor

Trials

4

Recruited

100+

Medpace, Inc.

Industry Sponsor

Trials

98

Recruited

30,400+

Dr. August J. Troendle

Medpace, Inc.

Chief Executive Officer since 1992

MD from the University of Maryland, School of Medicine; MBA from Boston University

Dr. Reinilde Heyrman

Medpace, Inc.

Chief Medical Officer since 2017

MD

Published Research Related to This Trial

A single dose of 20 Gy x-ray radiation significantly improved survival in rats with glioma, indicating its efficacy in treating this type of tumor.

The IMPULSED method of quantitative temporal diffusion spectroscopy effectively distinguished between irradiated and nonirradiated tumors by analyzing changes in cell size and structure, providing valuable insights into cellular responses to radiation that traditional imaging methods could not.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative temporal diffusion spectroscopy as an early imaging biomarker of radiation therapeutic response in gliomas: A preclinical proof of concept. Jiang, X., Xu, J., Gore, JC.[2022]

In a study of 1939 patients with brain metastasis who underwent stereotactic radiosurgery (SRS), 15% experienced radiation necrosis (RN), highlighting the need for careful monitoring and management of this potential side effect.

Several novel risk factors for RN were identified, including specific cancer histologies (like lung adenocarcinoma), HER2 amplification, and ALK/BRAF mutations, which could help tailor treatment plans and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Radiation Necrosis and Tumor Biology After Stereotactic Radiosurgery for Brain Metastasis. Miller, JA., Bennett, EE., Xiao, R., et al.[2022]

A systematic review of 22 studies found that amino acid PET (aaPET) is generally more effective than advanced MRI (aMRI) techniques for detecting brain tumors, predicting recurrence, and assessing patient survival.

Combining aaPET with advanced MRI methods, particularly diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI), significantly enhances diagnostic performance, making it the most effective approach for brain tumor imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Amino Acid PET to Advanced and Emerging MRI Techniques for Neurooncology Imaging: A Systematic Review of the Recent Studies. Stopa, BM., Juhász, C., Mittal, S.[2021]

In a study comparing NSG mice to other strains, it was found that NSG mice can safely receive radiation doses commonly used in experimental therapies without showing signs of brain toxicity, even at doses like 4 Gy and 5 × 2 Gy.

This suggests that NSG mice are suitable hosts for patient-derived orthotopic xenografts (PDOXs) in glioblastoma research, allowing for effective testing of combination therapies without the concern of radiation-induced damage to normal brain tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Brain Irradiation in Immune-Competent and Immune-Compromised Mouse Models. Saki, M., Bhat, K., Sodhi, SS., et al.[2021]

In a study involving 16 patients who underwent Gamma Knife radiosurgery, the combination of (18)F-FDG PET/CT and MRI demonstrated a sensitivity of 64.7% and a specificity of 100% in differentiating between adverse radiation effects and tumor recurrence.

The imaging technique was able to identify tumor presence within areas affected by radiation, suggesting it can be a valuable tool in managing post-radiosurgery cases by focusing on metabolic activity rather than just histological findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Although Non-diagnostic Between Necrosis and Recurrence, FDG PET/CT Assists Management of Brain Tumours After Radiosurgery. Torrens, M., Malamitsi, J., Karaiskos, P., et al.[2017]

In a review of 142 pediatric cases, radiation-induced second brain tumors were predominantly malignant gliomas, indicating a higher risk of aggressive tumors in children compared to adults.

The average latency for developing a second tumor in children was 8 years, while adults experienced a longer latency of 16 to 30 years, highlighting the increased vulnerability of the pediatric brain to radiation-induced complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation-induced brain tumours after central nervous system irradiation in childhood: a review. Pettorini, BL., Park, YS., Caldarelli, M., et al.[2021]

In a study involving 30 glioblastoma patients, using escalated radiation doses guided by metabolic abnormalities detected through spectroscopic MRI resulted in a median progression-free survival of 16.6 months, significantly improving outcomes compared to standard care.

The incidence rate of tumor recurrence at one year was reduced to 30% with this new treatment approach, compared to 60-70% recurrence rates typically seen with standard treatments, indicating a potential for better long-term management of glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Approach to Determining Tumor Progression Using a Three-Site Pilot Clinical Trial of Spectroscopic MRI-Guided Radiation Dose Escalation in Glioblastoma. Ramesh, KK., Huang, V., Rosenthal, J., et al.[2023]

The Brain Imaging Collaborative Suite's Longitudinal Imaging Tracker (BrICS-LIT) is a new cloud platform designed to improve the accuracy and objectivity of monitoring glioblastoma patients through semiautomated tumor segmentation of MRI scans.

By utilizing the BT-RADS framework, BrICS-LIT aims to provide quantitative metrics that can enhance clinical decision-making and potentially improve the assessment of novel therapies in glioblastoma patients during follow-up imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Longitudinal Imaging Tracker (BrICS-LIT):A Cloud Platform for Monitoring Treatment Response in Glioblastoma Patients. Ramesh, K., Gurbani, SS., Mellon, EA., et al.[2022]

The study developed a targeted imaging strategy using F(ab')2 fragments of an anti-EGFRvIII antibody linked to enzymes, which successfully enhanced MRI signal detection of aggressive brain tumors overexpressing the EGFRvIII variant.

Using SPECT/CT and 3T MRI, the researchers demonstrated that this method allows for high specificity and resolution in imaging tumor-specific receptors, indicating its potential for improved diagnosis and monitoring of brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR signal amplification for imaging of the mutant EGF receptor in orthotopic human glioma model. Shazeeb, MS., Gupta, S., Bogdanov, A.[2021]

In a study of 67 newly diagnosed glioma patients with 565 MRI scans, the one-dimensional (1D) and two-dimensional (2D) measurement methods showed good agreement for assessing tumor response, suggesting that RECIST criteria could be effectively used in glioma trials.

While different measurement methods provided similar assessments of tumor response, they did not correlate with overall patient survival, indicating that while RECIST may standardize response evaluation, it may not predict outcomes for glioma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of neuroradiologic response assessment in gliomas: measurement by RECIST, two-dimensional, computer-assisted tumor area, and computer-assisted tumor volume methods. Galanis, E., Buckner, JC., Maurer, MJ., et al.[2022]

Molecular imaging, particularly PET-CT and MRSI, significantly enhances cancer management by providing critical information that can lead to changes in treatment plans in up to 40% of cases.

MRSI, which avoids ionizing radiation, allows for safe and repeated monitoring of cancer metabolites, potentially improving early detection and treatment planning for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular imaging in the framework of personalized cancer medicine. Belkić, D., Belkić, K.[2015]

Imaging is crucial in neuro-oncology for diagnosing, planning treatment, and monitoring tumors, with advancements in quantitative imaging and radiomics enabling the creation of valuable databases for various applications.

The review highlights the need for standardization in imaging techniques and discusses the integration of advanced methods like radiomics and molecular imaging to improve outcomes in pediatric neuro-oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current state of pediatric neuro-oncology imaging, challenges and future directions. Nabavizadeh, A., Barkovich, MJ., Mian, A., et al.[2023]

Amino-acid PET imaging, particularly using 18F-DOPA, is increasingly recommended alongside MRI for evaluating and managing brain tumors, as it provides valuable insights at various stages of treatment.

There is strong evidence supporting the use of 18F-DOPA in adults for brain tumor evaluations, and emerging data suggests its effectiveness in pediatric cases as well, highlighting its potential for broader clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amino Acid PET Imaging with 18F-DOPA in the evaluation of Pediatric Brain Tumors. Djekidel, M., Alsadi, R., Bouhali, O., et al.[2022]

Magnetic Resonance Imaging (MRI) is the primary non-invasive method for diagnosing glioblastoma, but it has limitations in accurately depicting the tumor's complexity, often necessitating a brain biopsy for a definitive diagnosis.

Immuno-PET, which combines antibody specificity with the sensitivity of positron emission tomography, offers a promising non-invasive method for diagnosing and monitoring glioblastoma by providing detailed molecular insights that could enhance patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis of Glioblastoma by Immuno-Positron Emission Tomography. Ruiz-López, E., Calatayud-Pérez, J., Castells-Yus, I., et al.[2022]

Citations

1. targetedonc.com targetedonc.com/view/fda-grants-fast-track-designation-to-rad101-for-imaging-of-recurrent-brain-metastases

FDA Grants Fast Track Designation to RAD101 for Imaging ... Data from an earlier phase 2a trial conducted at Imperial College London demonstrated high uptake of RAD101 in both pretreated and treatment- ...

2. radiopharmtheranostics.com radiopharmtheranostics.com/rad-granted-us-fda-fast-track-for-rad101-metastases-imaging/

RAD Granted US FDA Fast Track for RAD101 Metastases ... including cerebral metastases. “The FDA's Fast Track Designation for RAD101 highlights the seriousness of recurrent brain metastases as a ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06777433

NCT06777433 | Phase 2b Imaging Study of RAD101 in ... This is an open-label, single dose, single arm, multicenter Phase 2b study to establish the imaging performance of RAD101 PET in participants who are ≥ 18 years ...

4. onclive.com onclive.com/view/fda-grants-fast-track-designation-to-rad101-for-imaging-of-brain-metastases

FDA Grants Fast Track Designation to RAD101 for Imaging ... RAD101 targets FASN, aiding in precise imaging of brain metastases, potentially improving diagnostic accuracy in differentiating tumor ...

5. cancernetwork.com cancernetwork.com/view/fda-grants-fast-track-designation-to-rad101-imaging-for-brain-metastases

FDA Grants Fast-Track Designation to RAD101 Imaging ... Secondary end points included the accuracy, sensitivity, and specificity of RAD101 in identifying tumor recurrence vs radiation necrosis in ...

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/568495

Phase 2b Imaging Study of RAD101 in Participants With ... Participant has one of the following histopathologically confirmed advanced solid tumors with known history of brain metastases: lung, breast, ...

7. clinicaltrialsarena.com clinicaltrialsarena.com/news/radiopharms-imaging-molecule-hits-mark-in-observational-trial/

Radiopharm's imaging molecule hits mark in observational ... Radiopharm Theranostics' novel imaging small molecule, RAD 101, has detected brain metastases in all 22 patients enrolled in an observational trial.

8. firstwordpharma.com firstwordpharma.com/story/6326407

Radiopharm Theranostics Provides Positive Clinical ... Preliminary data from first three patients in Phase 2b imaging clinical trial of RAD 101 show uptake in brain metastases from solid tumors, ...