SPECT Imaging for Pharmacokinetics and dosimEtry Towards TREATment Optimization

NCT ID: NCT06389097

Last Updated: 2025-03-07

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-02-03
• Study Completion Date: 2029-08-31

Brief Summary

The investigators will study SPECT imaging of radiopharmaceutical therapies given as standard of care or as part of other compatible research protocols. The goal is to validate the quantitative SPECT image reconstruction methods developed in this proposal, and to investigate the relation between dosimetry calculated from SPECT images and the outcomes. Patients will be recruited for SPECT/CT imaging during treatment. This is an observational study no additional new drugs or activities will be administrated. The investigators will perform SPECT imaging on a total of 80 patients (~20 each from year 2 to year 5). Each participant will be imaged 3 times after the first and last cycles of planned radiopharmaceutical therapy.

Detailed Description

Radiopharmaceutical therapy (RPT) is an emerging systemic treatment modality that delivers radiation to targeted cells. Recently FDA approved RPT agents include Radium-223 for prostate cancer, 177Lu-DOTATATE for neuroendocrine cancers, and 177Lu-PSMA-617 for prostate cancer. RPT is currently being administered as weight-based or fixed activities for 4-6 cycles, and there is concern that this standardized regimen compromises the potential efficacy of this treatment modality. In large part, this is because rigorous, validated dosimetry methods are not in standard clinical use, especially for alpha emitter RPTs. Such methods using SPECT would make it possible to predict potential normal organ toxicity and tumor response for individual patients. The multidisciplinary Johns Hopkins RPT research group has focused on development of such SPECT dosimetry methods and has an active NIH P01 grant for this work.

The ability to image and understand where the RPT distributes in patients makes it possible to estimate the radiation delivered to tissues. The study team of medical physics experts is developing quantitative 3-D, single-photon emission computed tomography (SPECT) imaging for dosimetry of beta and alpha emitters 1-9. Recognizing that such imaging must be made convenient to be widely adopted, the investigators are also examining the trade-off between simplifying imaging (shorter imaging times, fewer imaging sessions) and the accuracy of the absorbed dose calculations. Key barriers to implementing dosimetry for alpha emitters include the low count-rate and sub-optimal photon emissions and the emission of multiple daughter radionuclides. Currently available reconstruction methods in clinical SPECT systems cannot handle such complex imaging physics. The investigators have pioneered the development of simultaneous multiple radionuclide reconstruction methods for diagnostic applications.

The overall goal of this project is to develop imaging methodologies that may be used to perform accurate RPT dosimetry and treatment planning, especially for alpha emitters. Within this context, the SEE-to-TREAT protocol will provide clinical data and images to validate quantitative reconstruction methods for SPECT imaging.

Conditions

Prostate Cancer; Advanced Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Cohort A

Patients with advanced prostate cancer planning to undergo treatment with Radium-223

Radium-223

Intervention Type: RADIATION

Radium-223 will be given as per standard of care or other clinical trial. It is typically administered intravenously via slow injection once every 4 weeks with a dosage of 55 kBq/kg per cycle. Patients typically receive up to six cycles unless unacceptable toxic effects occurred, disease progression is apparent, or the patient is unable or unwilling to adhere to treatment.

Three SPECT/CT studies will be performed for research purposes after 2 cycles in patients who consent to participate in this imaging and dosimetry study. These will be performed at 2-4 hr, 24 hr, and 48 hr after any cycle of Radium-223. Protocol preference is for imaging with 2 cycles, ideally cycle 1 and cycle 6, but imaging with any one or two cycle(s) is acceptable.

The imaging time at each time point is approximately 30 minutes per field of view with two fields of view (1 hr total) typically collected sequentially (i.e., without repositioning the patient on the imaging table).

Cohort B

Patients with advanced cancer undergoing treatment with 177Lu-DOTATATE or 177Lu-PSMA-617

177Lu-DOTATATE

Intervention Type: RADIATION

177Lu-DOTATATE to be given as Standard of Care (SOC) or other clinical trial. It is typically infused intravenously over a period of 20-60 minutes with peptide co-infusion prior and during the infusion.

Patients will receive 4 cycles of 177Lu-DOTATATE administered approximately every 8 weeks. Treatment cycle is defined as 8 consecutive weeks (D1-D56) following a dose of 177Lu-DOTATATE. Patients receive up to four infusions of 7.4 GBq (200 mCi) every 8 weeks unless unacceptable toxic effects occurred, disease progression is apparent, or the patient is unable or unwilling to adhere to treatment.

Three SPECT/CT studies will be performed for research purposes after 2 cycles in patients who consent to participate in this imaging and dosimetry study. Lu-177 SPECT CT will be performed at 24 (D2), 48 (D3), and 96 (D5) of any cycle of therapy.

Imaging time at each time point is ~ 15-22 minutes per field of view with two fields of view (45 min total) typically collected sequentially.

177Lu-PSMA-617

Intervention Type: RADIATION

177Lu-PSMA-617 will be given as per SOC or other clinical trial. It is typically infused intravenously over a period of 20-60 minutes.

Up to 6 cycles of 177Lu- PSMA-617 will be administered approximately every 6 weeks. Treatment cycle is defined as 6 consecutive weeks (D1-D42) following a dose of 177Lu- PSMA-617. Patients will receive up to six infusions of 7.4 GBq (200 mCi) every 6 weeks unless unacceptable toxic effects occurred, disease progression is apparent, or the patient is unable or unwilling to adhere to treatment.

Three SPECT/CT studies will be performed for research purposes after 2 cycles in patients who consent to participate in this imaging and dosimetry study. Lu-177 SPECT CT will be performed at 24 (D2), 48 (D3), and 96 (D5) of any cycle of therapy.

Imaging time at each time point is approximately 15-22 minutes per field of view with two fields of view (45 min total) typically collected sequentially.

Interventions

Radium-223

Radium-223 will be given as per standard of care or other clinical trial. It is typically administered intravenously via slow injection once every 4 weeks with a dosage of 55 kBq/kg per cycle. Patients typically receive up to six cycles unless unacceptable toxic effects occurred, disease progression is apparent, or the patient is unable or unwilling to adhere to treatment.

Three SPECT/CT studies will be performed for research purposes after 2 cycles in patients who consent to participate in this imaging and dosimetry study. These will be performed at 2-4 hr, 24 hr, and 48 hr after any cycle of Radium-223. Protocol preference is for imaging with 2 cycles, ideally cycle 1 and cycle 6, but imaging with any one or two cycle(s) is acceptable.

The imaging time at each time point is approximately 30 minutes per field of view with two fields of view (1 hr total) typically collected sequentially (i.e., without repositioning the patient on the imaging table).

Intervention Type: RADIATION

177Lu-DOTATATE

177Lu-DOTATATE to be given as Standard of Care (SOC) or other clinical trial. It is typically infused intravenously over a period of 20-60 minutes with peptide co-infusion prior and during the infusion.

Patients will receive 4 cycles of 177Lu-DOTATATE administered approximately every 8 weeks. Treatment cycle is defined as 8 consecutive weeks (D1-D56) following a dose of 177Lu-DOTATATE. Patients receive up to four infusions of 7.4 GBq (200 mCi) every 8 weeks unless unacceptable toxic effects occurred, disease progression is apparent, or the patient is unable or unwilling to adhere to treatment.

Three SPECT/CT studies will be performed for research purposes after 2 cycles in patients who consent to participate in this imaging and dosimetry study. Lu-177 SPECT CT will be performed at 24 (D2), 48 (D3), and 96 (D5) of any cycle of therapy.

Imaging time at each time point is ~ 15-22 minutes per field of view with two fields of view (45 min total) typically collected sequentially.

Intervention Type: RADIATION

177Lu-PSMA-617

177Lu-PSMA-617 will be given as per SOC or other clinical trial. It is typically infused intravenously over a period of 20-60 minutes.

Up to 6 cycles of 177Lu- PSMA-617 will be administered approximately every 6 weeks. Treatment cycle is defined as 6 consecutive weeks (D1-D42) following a dose of 177Lu- PSMA-617. Patients will receive up to six infusions of 7.4 GBq (200 mCi) every 6 weeks unless unacceptable toxic effects occurred, disease progression is apparent, or the patient is unable or unwilling to adhere to treatment.

Three SPECT/CT studies will be performed for research purposes after 2 cycles in patients who consent to participate in this imaging and dosimetry study. Lu-177 SPECT CT will be performed at 24 (D2), 48 (D3), and 96 (D5) of any cycle of therapy.

Imaging time at each time point is approximately 15-22 minutes per field of view with two fields of view (45 min total) typically collected sequentially.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Cohort A: Patients with advanced prostate cancer planning to undergo treatment with Radium-223
• Cohort B: Patients with advanced cancer undergoing treatment with 177Lu-DOTATATE or 177Lu-PSMA-617

**Eligible patients may be planning to undergo these treatments as part of standard of care or as part of another research protocol

• Age > 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Histologic confirmation of malignancy

Exclusion Criteria

• Patient is participating in another research protocol that does not allow participation in this imaging protocol or that has schedule of procedures that would not be compatible with this protocol.
• Patient unable to tolerate SPECT scan time, scan frequency, or position.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ana Kiess, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ana Kiess

Role: CONTACT

akiess1@jhmi.edu

443-287-7528

Ryan Manuel

Role: CONTACT

rmanuel5@jhmi.edu

410-955-4261

Other Identifiers

IRB00411454

Identifier Type: OTHER

Identifier Source: secondary_id

P01CA272222

Identifier Type: NIH

Identifier Source: secondary_id

View Link

J23152

Identifier Type: -

Identifier Source: org_study_id