A Trial of CTT1403 for Metastatic Castration Resistant Prostate Cancer

NCT03822871 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: CTT1403-1015R44CA239461-06
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Prostate Cancer

Keywords

prostate cancer; metastatic castration resistant prostate cancer; prostate specific membrane antigen; mCRPC; PSMA; positron emission tomography; PET; radiotherapy; targeted therapy; lutetium; 177Lu

Outcome Measures

Primary Outcomes (2)

• Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403

  The dose-limiting toxicity was defined as any of the following: 1. Grade 4 neutropenia lasting \> 5 consecutive days 2. Grade 3 or 4 febrile neutropenia 3. Grade 4 thrombocytopenia lasting ≥ 7 days, or Grade 3 or 4 thrombocytopenia with clinically significant bleeding or requirement for platelet transfusion 4. 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 5. 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 Outcomes (3)

• Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging

  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

  Cycle 1-Day 1 and Cycle 2-Day 1. Each cycle lasted 35 days.

• Assessment of Pharmacokinetics of CTT1403

  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)

Study Arms (2)

Dose Escalation

EXPERIMENTAL

Escalating doses of 0.75 GBq - 2.0 GBq of CTT1403

Drug: CTT1403; Drug: CTT1057; Drug: 68Ga-PSMA-11

Dose Escalation/Expansion

EXPERIMENTAL

Escalating doses of 3.0 GBq - 9.0 GBq of CTT1403

Drug: CTT1403; Drug: CTT1057; Drug: 68Ga-PSMA-11

Interventions

CTT1403 DRUG

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.

Dose Escalation; Dose Escalation/Expansion

CTT1057 DRUG

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.

Dose Escalation; Dose Escalation/Expansion

68Ga-PSMA-11 DRUG

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.

Dose Escalation; Dose Escalation/Expansion

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Prostate cancer is a disease only occurring in males.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cancer Targeted Technology: lead
• University of California, San Francisco: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 9410794143, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

gallium 68 PSMA-11

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Limitations and Caveats

The highest administered dose of CTT1403 was 9.0 GBq. At the 9.0 GBq dose, patients had to remain in-patient (in hospital) after administration due to continued radioactivity and for the safety of others until radioactivity dropped to an acceptable level as deemed by the hospital radiation safety committee.

Results Point of Contact

• Title: Dr. Beatrice Langton-Webster, CEO
• Organization: Cancer Targeted Technology

bealw@cancertargetedtechnology.com

(206) 617-0699

Study Officials

• Beatrice Langton-Webster, PhD

  Cancer Targeted Technology

  STUDY CHAIR

• Rahul Aggarwal, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: January 30, 2019
• Study Start: April 1, 2019
• Primary Completion: October 28, 2022
• Study Completion: February 8, 2023
• Last Updated: March 21, 2024
• Results First Posted: March 21, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)