A Trial of CTT1403 for Metastatic Castration Resistant Prostate Cancer

A Phase 1 Trial for Evaluation of Safety and 177Lu Radiation Dosimetry of CTT1403: A Peptidomimetic Inhibitor of Prostate Specific Membrane Antigen, in Metastatic Castration Resistant Prostate Cancer (mCRPC)

The purpose of this study is to find the highest dose level of study drug, CTT1403, that can be safely administered to patients with metastatic castration resistant prostate cancer (mCRPC).

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: CTT1057; Drug: 68Ga-PSMA-11; Drug: CTT1403

Detailed Description

This is a Phase 1, first-in-human dose escalation/dose expansion study evaluating escalating doses of CTT1403 in patients with PSMA-avid mCRPC with progressive disease on at least one androgen signaling inhibitor, followed by a dose expansion to further evaluate the safety, tolerability, efficacy and biological activity of CTT1403. CTT1403 is a PSMA-targeted 177Lu-labeled radiotherapy being developed for prostate cancer with a unique PSMA binding scaffold and an albumin binding moiety to extend circulation half-life. The PSMA binding scaffold is shared with CTT1057, a PSMA-specific PET diagnostic imaging agent shown in Phase 1 clinical trials to be specifically taken up by PSMA+ tumor. PSMA PET imaging by CTT1057 will be used diagnostically to select patients with PSMA-avid disease for treatment. The purpose of this study is to identify the dose limiting toxicity and recommended phase 2 dose of CTT1403. Eligible participants with demonstrated therapeutic benefit will be offered a second dose of study drug.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 9410794143
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients must have histologically confirmed prostate adenocarcinoma that is metastatic and castration resistant (mCRPC).
• At least 3 metastatic foci avid for PSMA-specific PET agent (CTT1057) uptake on Screening PSMA PET.
• Has received docetaxol, ineligible for docetaxol, or refused docetaxol for the treatment of prostate cancer.
• Has progression by the PCWG3 criteria during or after treatment with either abiraterone or enzalutamide
• Male Age ≥ 18 years.
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix 2).
• Demonstrate adequate organ function

Exclusion Criteria:

• Has received previous treatment with radium-223 or another radiopharmaceutical within 3 months prior to first dose of CTT1403.
• Has received prior systemic anti-cancer therapy (excluding radiopharmaceutical) within 14 days, or 5 half-lives, whichever is shorter, prior to first dose of CTT1403.
• Has received external-beam radiation within 14 days prior to first dose of CTT1403.
• Has received cabazitaxel for the treatment of mCRPC.
• Has received previous treatment with a therapeutic targeting PSMA.
• Has an additional active malignancy requiring therapy that may confound the assessment of the study endpoints.
• Has clinically significant cardiovascular disease
• Has a history of untreated brain metastases
• Has evidence of diffuse bone marrow involvement by prostate cancer in the judgment of study investigator.
• Clinically significant urinary obstruction or moderate/severe hydronephrosis on baseline imaging.
• Has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days before CTT1403 administration.
• Has known positive status for chronic hepatitis B or hepatitis C
• Known or suspected myelodysplastic syndrome.
• Has any medical condition which in the opinion of the Investigator places the patient at an unacceptably high risk for toxicities.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Escalating doses of 0.75 GBq - 2.0 GBq of CTT1403	Drug: CTT1057; Patients will be screened with CTT1057 or 68Ga-PSMA-11 PSMA PET to demonstrate presence of at least 3 PSMA avid lesions that can be targeted by the study drug, CTT1403. 5-7 weeks after administration of study drug, patients will be evaluated a second time with PSMA PET imaging using with either CTT1057 or 68Ga-PSMA-11 to assess potential efficacy of CTT1403.; Drug: 68Ga-PSMA-11; Patients will be screened with CTT1057 or 68Ga-PSMA-11 PSMA PET to demonstrate presence of at least 3 PSMA avid lesions that can be targeted by the study drug, CTT1403. 5-7 weeks after administration of study drug, patients will be evaluated a second time with PSMA PET imaging using with either CTT1057 or 68Ga-PSMA-11 to assess potential efficacy of CTT1403.; Drug: CTT1403; Escalating doses of 0.75 GBq - 9.0 GBq will be administered in an accelerated to traditional 3+3 dose escalation design. After escalation, 10 additional patients will be enrolled into a dose expansion cohort. Patients meeting eligibility criteria with demonstrated cessation of disease progression will be offered a second dose of the study drug, CTT1403.
Experimental: Dose Escalation/Expansion; Escalating doses of 3.0 GBq - 9.0 GBq of CTT1403	Drug: CTT1057; Patients will be screened with CTT1057 or 68Ga-PSMA-11 PSMA PET to demonstrate presence of at least 3 PSMA avid lesions that can be targeted by the study drug, CTT1403. 5-7 weeks after administration of study drug, patients will be evaluated a second time with PSMA PET imaging using with either CTT1057 or 68Ga-PSMA-11 to assess potential efficacy of CTT1403.; Drug: 68Ga-PSMA-11; Patients will be screened with CTT1057 or 68Ga-PSMA-11 PSMA PET to demonstrate presence of at least 3 PSMA avid lesions that can be targeted by the study drug, CTT1403. 5-7 weeks after administration of study drug, patients will be evaluated a second time with PSMA PET imaging using with either CTT1057 or 68Ga-PSMA-11 to assess potential efficacy of CTT1403.; Drug: CTT1403; Escalating doses of 0.75 GBq - 9.0 GBq will be administered in an accelerated to traditional 3+3 dose escalation design. After escalation, 10 additional patients will be enrolled into a dose expansion cohort. Patients meeting eligibility criteria with demonstrated cessation of disease progression will be offered a second dose of the study drug, CTT1403.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403	The dose-limiting toxicity was defined as any of the following: Grade 4 neutropenia lasting > 5 consecutive days; Grade 3 or 4 febrile neutropenia; Grade 4 thrombocytopenia lasting ≥ 7 days, or Grade 3 or 4 thrombocytopenia with clinically significant bleeding or requirement for platelet transfusion; Any nonhematologic, treatment-related AE ≥ Grade 3, with the exceptions of Grade 3 nausea, vomiting, diarrhea, non-clinically significant electrolyte abnormality, constipation, fever, fatigue, or skin rash that resolves to Grade ≤ 2 within 72 hours with optimal medical management; Any other treatment-related toxicity that results in delay of Cycle 2 administration of CTT1403 by > 21 days and/or toxicity considered by the Investigator and Sponsor's medical representatives to be dose-limiting.	6-8 weeks from time of injection on Cycle 1 - Day 1
Objective Response Rate by RECIST v1.1 Criteria	Changes in only the largest diameters (unidimensional measurment) of the tumor lesions are used in the RECIST v1.1 criteria. Data presented as RECIST Overall Response.	Cycle 1-Day 35, Cycle 2-Day 35, 30 Days After Last Dose, 8 Weeks Post-Treatment. Each cycle lasted 35 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging	Organ dosimetry was assessed via SPECT/CT imaging until two imaging periods have been collected in which study drug cannot be detected by SPECT/CT. Time points included (2 hrs ± 1 followed by 24±12 hrs, 48±12 hrs, and 168±24 hrs post-infusion on Cycle 1-Day 1. Data calculated using OLINDA. Absorbed dose is calculated as single value wherein absorbed dose is proportional to the integral of activity over time.	2 hrs ± 1 followed by 24±12 hrs, 48±12 hrs, and 168±24 hrs post-infusion on Cycle 1-Day 1
Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index	The Brief Pain Index uses a scale of 0-10 to rate the severity of pain. A rating of 0 indicates no pain. A rating of 10 indicates the worst pain imaginable.	Cycle 1-Day 1 and Cycle 2-Day 1. Each cycle lasted 35 days.
Assessment of Pharmacokinetics of CTT1403	The distribution half-life and the elimination half-life of CTT1403 were calculated.	Samples were collected during Cycle 1 (timepoints start at the initiation of infusion): Day 1 (30 min +/- 5 min and 2 hrs +/- 30 min), Day 2 (24 hrs +/- 12 hrs), Day 3 (48 hrs +/- 12 hrs), Day 8 (168 hrs +/- 24 hrs), Day 15 (336 hrs +/- 24 hrs)

Collaborators and Investigators

• Sponsor: Cancer Targeted Technology
• Collaborators: National Cancer Institute (NCI); University of California, San Francisco
• Investigators: Principal Investigator: Rahul Aggarwal, MD, University of California, San Francisco; Study Chair: Beatrice Langton-Webster, PhD, Cancer Targeted Technology

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): October 28, 2022
• Study Completion (Actual): February 8, 2023

Study Registration Dates

• First Submitted: January 28, 2019
• First Submitted That Met QC Criteria: January 29, 2019
• First Posted (Actual): January 30, 2019

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: PET; prostate cancer; radiotherapy; metastatic castration resistant prostate cancer; prostate specific membrane antigen; mCRPC; PSMA; positron emission tomography; targeted therapy; lutetium; 177Lu
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Gallium 68 PSMA-11
• Other Study ID Numbers: CTT1403-101; 5R44CA239461-06 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No