RAD101 Imaging for Brain Cancer

(RAD101 Trial)

Recruiting at 2 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

Trial Summary

What is the purpose of this trial?

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 of age and with suspected recurrent brain metastases from solid tumors. The study consists of a 4-week Screening Period, a 3-day Imaging and Safety Follow-Up Period, and a Data Collection Period of up to 6 months. Participant eligibility will be determined during the Screening Period and eligible participants will be enrolled in the study. On Day 1, the enrolled participants will receive a single dose of the investigational medicinal product (IMP), RAD101. Participants will then proceed with a whole brain PET scan. A high-resolution Magnetic Resonance Imaging (MRI) will be performed in joint acquisition with PET or separately on the same day. A phone follow-up will be performed on Day 3 (+ 1 day). Participants will have follow-up (longitudinal) MRI scans (longitudinal imaging) and/ or a biopsy according to their Standard of Care (SoC). The longitudinal MRI results, and details of the biopsy if performed as part of SoC (i.e., location and histopathology results), will be collected during the 6- month Data Collection Period.

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 data supports the effectiveness of the treatment RAD101 for brain cancer?

The research highlights the use of advanced imaging techniques like spectroscopic MRI and molecular imaging, which can improve the assessment of brain tumors and guide treatment decisions. These methods have shown potential in enhancing the accuracy of tumor progression monitoring and treatment response, which could indirectly support the effectiveness of RAD101 in brain cancer treatment. ^{1 2 3 4 5}

Is RAD101 imaging for brain cancer safe for humans?

The research suggests that radiation treatments, like those used in RAD101 imaging, can sometimes cause side effects such as radiation necrosis (damage to brain tissue), which occurs in about 5% to 10% of cases. However, studies in mice have shown that certain radiation doses do not cause noticeable brain damage, indicating that similar doses might be safe in humans. ^{6 7 8 9 10}

How is the treatment RAD101 different from other brain cancer treatments?

RAD101 Imaging for Brain Cancer may involve advanced imaging techniques like amino acid PET, which can provide more accurate detection and evaluation of brain tumors compared to traditional MRI. This approach could offer better insights into tumor characteristics and treatment planning. ^{6 11 12 13 14}

Research Team

Dimitris Voliotis, MD

Principal Investigator

Radiopharm Theranostics

Eligibility Criteria

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.

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

I can take care of myself and am up and about more than half of the day.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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 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 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]

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]

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]

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]

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]

References

1. England 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. [2022]

2. Switzerland 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. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

The Longitudinal Imaging Tracker (BrICS-LIT):A Cloud Platform for Monitoring Treatment Response in Glioblastoma Patients. [2022]

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

MR signal amplification for imaging of the mutant EGF receptor in orthotopic human glioma model. [2021]

5. Israel pubmed.ncbi.nlm.nih.gov

Molecular imaging in the framework of personalized cancer medicine. [2015]

6. Greece pubmed.ncbi.nlm.nih.gov

Although Non-diagnostic Between Necrosis and Recurrence, FDG PET/CT Assists Management of Brain Tumours After Radiosurgery. [2017]

7. United States 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. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Radiation-induced brain tumours after central nervous system irradiation in childhood: a review. [2021]

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

Association Between Radiation Necrosis and Tumor Biology After Stereotactic Radiosurgery for Brain Metastasis. [2022]

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

Effects of Brain Irradiation in Immune-Competent and Immune-Compromised Mouse Models. [2021]

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

Current state of pediatric neuro-oncology imaging, challenges and future directions. [2023]

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

Amino Acid PET Imaging with 18F-DOPA in the evaluation of Pediatric Brain Tumors. [2022]

13. England 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. [2021]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Diagnosis of Glioblastoma by Immuno-Positron Emission Tomography. [2022]