Phase I Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of the Bispecific Antibody CC-1 in Men With Biochemical Recurrence of Prostate Cancer
Overview
- Phase
- Phase 1
- Intervention
- CC-1 Infusion
- Conditions
- Prostate Cancer Recurrent
- Sponsor
- University Hospital Tuebingen
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- Dose escalation part: To define the maximum tolerated dose (MTD) of CC-1 as 3 hours infusion
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This trial is a phase I open-label, single center study designed to evaluate the safety, tolerability and preliminary efficacy of the bispecific prostate specific membrane antigen (PSMA) and cluster of differentiation protein 3 (CD3) antibody CC-1 in men with biochemical recurrence (BCR) of prostate cancer (PC). The PSMA binder in CC-1 reacts with tumor cells and also binds to tumor vessels, thereby allowing for a dual mode of anti-cancer action. CC-1 was developed in a novel format, which not only prolongs serum half-life, but most importantly reduces off-target T-cell activation with accordingly reduced side effects. The study entails a part I (dose escalation part) to identify the maximally tolerated dose of CC-1, which then will be further evaluated in part II of the study (dose expansion part). After application of two low doses as safety steps in the first cycle, CC-1 will be applied twice weekly for three consecutive weeks within 4 week cycles as a short-term intravenous infusion (3 hours). The planned trial ultimately shall define the recommended phase II dose (RP2D) of CC-1 in the disease setting of BCR of PC.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent
- •Patient is able to understand and comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
- •Men aged 18 and above
- •Earlier histologic diagnosis of prostatic adenocarcinoma
- •Low risk of rapid disease progression, defined as:
- •PSA-detection Time (DT) \> 1 year AND pathological International Society of Urological Pathology (ISUP) grade \< 4 for men with prior radical prostatectomy or Interval to biochemical recurrence \> 18 months and biopsy ISUP grade \< 4 for men with prior radiation therapy
- •Biochemical recurrence (BCR) in compliance with the following 3 conditions:
- •after having finished last definitive treatment
- •PSA ≥0.2 ng/mL or PSA \> nadir + 2 ng/mL (after definitive RT), with two increasing PSA values prior to study treatment
- •no distant metastasis upon PSMA- positron emission tomography (PET) imaging
Exclusion Criteria
- •PSA \>5 ng/ml.
- •For men with prior radical prostatectomy:
- •PSA-DT \< 1 year or
- •pathological ISUP grade 4-5
- •For men with prior radiation therapy:
- •Interval to biochemical recurrence \< 18 months or
- •biopsy ISUP grade 4-5
- •Other malignancy within the last 2 years except: adequately treated non-melanoma skin cancer and low-grade non-muscle invasive papillary bladder cancer.
- •Concurrent or previous treatment within 30 days in another interventional clinical trial with an investigational anticancer therapy
- •Patients who are receiving androgen-deprivation therapy.
Arms & Interventions
Dose Escalation Part
In the dose escalation part, up to 7 dose cohorts will be included depending on occurrence of dose-limiting toxicity (DLT). Each dose cohort has a predefined day 3 dose level (DL): cohort 1, 78µg; cohort 2, 110µg; cohort 3, 150µg; cohort 4, 210µg; cohort 5, 300µg; cohort 6, 400µg; cohort 7, 600µg. Each dose cohort will consist of at least three patients evaluable for DLT. Maximum tolerated dose (MTD) is defined on at least six patients
Intervention: CC-1 Infusion
Dose Expansion Part
CC-1 is administered as a 3-hour short-term intravenous infusion started at the MTD dose level identified in the dose escalation part of the study or based on the discretion of the sponsors delegate and DSMB recommendation supported by preliminary safety and efficacy data to constitute a modified MTD, e.g. to be one or more dose levels lower than the MTD determined. Patients can be treated simultaneously during the dose expansion phase. Patients must be hospitalized during step dosing, i.e. from day 1-4 (last dosing on day 3) of the first cycle. Thereafter inpatient treatment (overnight stay) depends on the discretion of the investigator, an outpatient treatment is preferred.
Intervention: CC-1 Infusion
Outcomes
Primary Outcomes
Dose escalation part: To define the maximum tolerated dose (MTD) of CC-1 as 3 hours infusion
Time Frame: during the procedure
Data Safety and Monitoring Board (DSMB) and Sponsor meeting about determination of the MTD for each cohort and the dose expansion phase
Dose expansion part: To define the recommended phase-II dose of CC-1
Time Frame: up to 1 month after procedure
Data Safety and Monitoring Board and Sponsor meeting about determination of the recommended phase II dose of CC-1 for potential phase II trials.
Secondary Outcomes
- To evaluate safety and tolerability of CC-1(during the procedure)
- To assess CC-1 serum concentrations(during the procedure prior to and after start of infusion on each treatment day in the first cycle (each cycle is 28 days).)
- To assess clinical outcome in terms of progression-free survival, treatment-free survival, overall survival(through study completion, an average of 6 months)
- To assess efficacy in terms of Prostata-Specific-Antigen (PSA) response and no PSA progression after CC-1 treatment(during the procedure and through study completion, an average of 6 months)
- To assess quality of life(through study completion, an average of 1 year)