the Bispecific PSMAxCD3 Antibody CC-1 in Patients With Castration Resistant Prostate Carcinoma (PSMAxCD3)
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|ClinicalTrials.gov Identifier: NCT04104607|
Recruitment Status : Recruiting
First Posted : September 26, 2019
Last Update Posted : November 19, 2019
|Condition or disease||Intervention/treatment||Phase|
|Castration-Resistant Prostatic Cancer||Drug: CC-1, PSMAxCD3||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||86 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Open-label, multicenter dose escalation and dose expansion phase I trial, designed to gain evidence of maximally tolerated and recommended phase-II dose of CC-1 in adult patients with CRPC.|
|Masking:||None (Open Label)|
|Official Title:||First in Human Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of the Bispecific PSMAxCD3 Antibody CC-1 in Patients With Castration Resistant Prostate Carcinoma|
|Actual Study Start Date :||November 15, 2019|
|Estimated Primary Completion Date :||March 1, 2020|
|Estimated Study Completion Date :||September 1, 2022|
Experimental: CC-1 therapy
Infusion of CC-1 over 24 hours for 7 days with possible intra-patient dose-escalation. In case of clinical benefit, additional cycles with a total of up to six are possible.
Drug: CC-1, PSMAxCD3
Infusion of CC-1 over 24 hours for 7 days with possible intra-patient dose-escalation
- Incidence and severity of adverse events (AEs) (CTCAE V5.0) over 21 days (i.e. until end of first treatment cycle (day 28)) [ Time Frame: Each cycle is 28 days; Safety Assessment on day 1-9,15,22,28 ]Grade 1 No interruption- No dose adjustment Grade 2 Interrupt until Grade 0/1- No dose adjustment Any Grade ≥ 3 Interrupt until Grade 0/1 Permanently stop, except that no DLT is caused; if the latter and if AE is resolved to Grade 0/1, resume with dose reduction by two dose levels
- Immunogenicity: [ Time Frame: at day 90 of the last cycle of a given patient ]Number and percentage of subjects who develop HAHA at day 21 of every cycle and EOSf as compared to baseline.
- Cytokine induction [ Time Frame: baseline and at day 1-9, day 15 and day 21 in the first cycle. ]Cytokines levels in serum as assessed at baseline and at day 1-9, day 15 and day 21 in first cycle. The panel of the assay contains rather T cell specific cytokines, such as IL-2, as well as cytokines produced by a broader range of cells (e.g. IFN-ɣ, TNF, etc.) and in particular IL-6 and IL-1β, the effects of former to be blocked by tocilizumab during the study, the latter associated in recent reports with the induction of central nervous system complications during cytokine release. Cytokine levels in samples are measured centrally at the Tübingen site. Serum samples from the other sites are shipped to Universitätsklinikum Tübingen. A commercially available, flow cytometry-based assay will be used (LEGENDplexTM, Biolegend) that allows parallel determination of different cytokines in one serum sample.
- Measurment of the CC-1 blood serum concentration [ Time Frame: At Day1-7, 15 and 21 in the first cycle ]
Determination of the CC-1 blood serum concentrations assessed at day 1-7, 15 in the first cycle; Samples for pharmacokinetics (5ml serum) should be collected immediately prior to each single CC-
1 application and 2h, 4h, 8h and 24h after completion of the last dose as well as on day 15 and 21.
An established potency assay for CC-1 that takes advantage of genetically engineered Jurkat T cells that express a luciferase reporter driven by an NFAT-response element (Promega assay). Using 22RV1 prostate carcinoma cells as PSMAexpressing target cells, the biological activity of the antibody is determined by analysis of CD3-induced luciferase activity in the effectorcell which can be quantified by luminescence assays. Serum levels can then be determined by comparison with luminescence levels induced by a reference standard.
- Anti-tumor activity [ Time Frame: day 8, 15 and d21 of each cycle, and at day 90 after last cycle of given patient ]Absolute changes from baseline in the tumor-marker PSA Measurement
- Anti-tumor activity [ Time Frame: at day 90 and thereafter for 6 months every 3 months after last cycle of given patient ]Objective tumor response assessed by RECIST on routine imaging
- Survival [ Time Frame: one year after day 90 ]overall and progression free survival status as percentage of patients alive
- Quality of life Assessment according to EORTC QLQ C-30 form [ Time Frame: baseline, day 8, 21, 90 (EOSf) and 6 months after start of CC-1 treatment. ]
QoL is defined as overall quality of life scores (EORTC QLQ C-30) at baseline, day 8, day 21, EOSf and 6 months after start of CC-1 treatmentOverall quality of life scores (EORTC QLQ C-30) The QoL analyses will be performed as previously described. The QoL scales will be scored and analysed according to the EORTC recommendations as described in the EORTC QLQ-C30 scoring manual. The Quality of Life subscales and single item sub-scores will be summarized by the mean and median and plotted by time. The change from baseline for all domains will be examined. Overall quality of life scores will be assessed with the EORTC QLQ C-30 questionnaire (https://www.onkopedia.com/de/wissensdatenbank/wissensdatenbank/allgemeinzustand/EORT CQLQC30.pdf).
Scale is 1 to 4 corresponding with (1) not at all, (2) a little, (3) quite a bit, (4) verymuch
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04104607
|Contact: Helmut R Salih, Prof.||+49 (0)7071 email@example.com|
|Contact: Juliane Walz, PD Dr. med.||+49 (0)7071 firstname.lastname@example.org|
|University Hospital Tuebingen||Recruiting|
|Tuebingen, Baden-Wuerttemberg, Germany, 72076|
|Contact: Helmut R Salih, Prof. +49(0)707129 ext 83275 email@example.com|
|Contact: Juliane walz, PD Dr. +49(0)707129 ext 87305 firstname.lastname@example.org|
|University hospital Heidelberg||Not yet recruiting|
|Heidelberg, BadenWuerttemberg, Germany, 69120|
|Contact: Richard Schlenk, Prof. +49 (0)6221 56-6228 email@example.com|
|Principal Investigator:||Helmut R Salih, Prof.||KKE Translational Immunology, University Hospital Tübingen|