64Cu-DOTA Pembrolizumab for Imaging Metastatic Solid Tumors in Patients Receiving Stereotactic Body Radiation

Pilot Trial Using 64Cu-DOTA Pembrolizumab (64CDP) in Patients Receiving Stereotactic Body Radiation Therapy for Oligo-Progressive Solid Tumors

This clinical trial tests how well using 64Cu-DOTA pembrolizumab (64CDP) with positron emission tomography (PET) scans works to find tumor cells in patients with cancers that have spread from where it first started to other places in the body (metastatic). 64CDP is a compound with pembrolizumab that is joined with a radioactive substance used for diagnostic purpose. Pembrolizumab is in a class of medications called monoclonal antibodies. It works by helping your immune system to slow or stop the growth of cancer cells. Targeted drugs such as pembrolizumab may the improve uptake of the radioactive substance in tumor cells. 64CDP may improve ability to evaluate response to treatment in patients with solid tumors.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Malignant Solid Neoplasm
• Intervention / Treatment: Radiation: Stereotactic Body Radiation Therapy; Procedure: Positron Emission Tomography; Drug: Copper Cu 64-DOTA-pembrolizumab

Detailed Description

PRIMARY OBJECTIVES:

I. To describe toxicities of 64Cu-DOTA-pembrolizumab (64CDP) positron emission tomography, by evaluation of toxicities including: type, frequency, severity, attribution, time course, and duration.

II. To identify changes in 64Cu-DOTA-pembrolizumab (64CDP) uptake in radiated metastatic lesions pre- and post-SBRT.

OUTLINE:

Patients receive standard of care pembrolizumab intravenously (IV) at baseline. Patients then receive 64CDP IV days 1 and 29 on study. Patients undergo PET scan on days 2 and 30 on study. Patients also undergo standard of care SBRT days 8-18.

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorized representative.

  • Assent, when appropriate, will be obtained per institutional guidelines
• Age: >= 18 years
• Karnofsky performance status (KPS) >=70
• Patients with metastatic disease from a solid-tumor malignancy currently being treated with single-agent pembroilizumab, who have been referred for stereotactic body radiation therapy (SBRT) for consolidative local therapy or for oligo resistant/progressive disease
• Sites that amenable to SBRT are located in lymph nodes, bone/spine, or lung
• Brain metastases or cases with intra-cranial progression are allowed, but an additional extra-cranial site planned for SBRT is required
• Absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 50/mm^3; platelet transfusions to help patients meet eligibility criteria are not allowed within 7 days before study enrollment
• Total bilirubin =< 1.5 x the upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
• Calculated creatinine clearance >= 30mL/min

• Contraception:

  • Woman of childbearing potential must be practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods; condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization; true abstinence (when this is in line with the preferred and usual lifestyle of the subject) during and after the study (6 months after the last dose of 64Cu-anti-PD1 [pembrolizumab]-NHS-DOTA for women);
  • A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control, e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 6 months after receiving the last dose of study drug

Exclusion Criteria:

• Patient planned to stop Pembrolizumab at time of referral for SBRT
• Patient unable to tolerate positron emission tomography (PET) scan even with anxiolytic medications
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Vaccination with live attenuated vaccines within 4 weeks of study agent administration except forthcoming COVID-19 vaccines

• Subject is currently using or has used immunosuppressive medication within 14 days prior to the study agent administration with the exception of:

  • Intranasal, topical, inhaled, or local steroid injections (e.g., intra-articular injection);
  • Chronic systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent;
  • Steroids as premedication for hypersensitivity reactions (e.g., infusion-related reactions, CT scan premedication)
• Female patients who are lactating or have a positive pregnancy test during the screening period
• Infection requiring systemic antibiotic therapy within 14 days prior to start of study treatment
• Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary amyloidosis
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (64CDP PET); Patients receive standard of care pembrolizumab IV at baseline. Patients then receive 64CDP IV days 1 and 29 on study. Patients undergo PET scan on days 2 and 30 on study. Patients also undergo standard of care SBRT days 8-18.

Radiation: Stereotactic Body Radiation Therapy; Undergo SBRT; Other Names: SBRT; SABR; Stereotactic Ablative Body Radiation Therapy; Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Drug: Copper Cu 64-DOTA-pembrolizumab; Given IV; Other Names: 64Cu-DOTA-pembrolizumab; 64Cu-labeled Pembrolizumab; 64Cu-pembrolizumab; Copper Cu 64 Pembrolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicities (DLT)	Defined as any infusion-related reactions, hematologic or non-hematologic toxicities that occur during the first 3 days post administration of study drug that are possibly related to protocol therapy. DLT adverse events will be monitored continuously. Toxicities will be summarized in terms of type, severity, time of onset, duration, and association with study treatment.	After administration of study treatment up to 1 month
Changes in 64CDP uptake	T-test to determine significance. T-tests (paired) will be used to test changes in 64-CDP uptake in radiated metastatic lesions pre- and post-SBRT.	From baseline through study completion, an average of 6 weeks
Change in standard-uptake-value (SUV-max)	T-test to determine significance.	From baseline through study completion, an average of 6 weeks
Incidence of adverse events	Defined as any infusion-related reactions, hematologic or non-hematologic toxicities that occur during the first 3 days post administration of study drug that are possibly related to protocol therapy. Dose limiting toxicity (DLT) adverse events will be monitored continuously. Toxicities will be summarized in terms of type, severity, time of onset, duration, and association with study treatment.	After administration of study treatment up to 1 month

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Sagus Sampath, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): August 25, 2023
• Primary Completion (Estimated): November 8, 2026
• Study Completion (Estimated): November 8, 2026

Study Registration Dates

• First Submitted: January 3, 2023
• First Submitted That Met QC Criteria: February 13, 2023
• First Posted (Actual): February 15, 2023

Study Record Updates

• Last Update Posted (Estimated): October 9, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trace Elements; Micronutrients; Immune Checkpoint Inhibitors; Copper; Pembrolizumab
• Other Study ID Numbers: 22305 (Other Identifier: City of Hope Comprehensive Cancer Center); P30CA033572 (U.S. NIH Grant/Contract); NCI-2022-10254 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No