Metastatic Castration-resistant Prostate Cancer (CRPC)
Conditions
Keywords
hyperthermia, immune checkpoint inhibitor, RTK inhibitor, CRPC
Brief summary
In this study, we propose to use the combination of ET-SPACE NIR irradiation whole-body thermal stimulation, ICI (Tislelizumab), and RTK inhibitor (Anlotinib) in the multimodal treatment of CRPC.
Detailed description
The initial efficacy and safety of the multimodal therapy will be evaluated at the animal level to fully validate the potential feasibility of the therapy. Subsequently, the efficacy of the multimodal therapy will be verified at the organoid level, and based on which a translational randomized controlled clinical trial will be conducted to evaluate the efficacy and safety of the multimodal therapy at the human level, and the patients will be followed up for a long period of time, so as to collect detailed data on improvement of the quality of life. Finally, the synergistic effect of the multimodal therapy will be analyzed at the molecular and cellular levels.
Interventions
DRUGImmunotherapy
Immunotherapy is currently a hot spot in the field of tumor research. Immune Checkpoint Inhibitor (ICI) is a monoclonal antibody designed to target the negative immunoregulatory pathway overexpressed in tumor cells, which can release the anti-tumor immunosuppressive signals and restore the killing of tumors by the immune cells, and thus exert anti-tumor effects. ICI regimen: Tislelizumab, 200mg, ivgtt., d1, q21d.
DRUGTargeted therapy
Recent studies have found that the combination of RTK inhibitors and ICIs can exert synergistic effects on different mechanisms, which can compensate for the deficiencies of single-agent RTK inhibitors and single-agent ICIs in the treatment of CRPC and become a potential novel therapeutic strategy for solid malignant tumors. RTK inhibitor regimen: Anlotinib, 12mg, po., d2\ 15, q21d.
DEVICEHyperthermia
Thermal stimulation is a rapidly developing physiotherapeutic tool, which is playing an increasingly important role in the field of comprehensive tumor therapy due to its unique low adverse effects and high compatibility. A large number of clinical studies have shown that the addition of heat stress to multimodal tumor therapy does not significantly increase toxicity and side effects, and the combination of heat stress with other therapies can have the effect of 1+1\>2. ET-SPACE near-infrared irradiation whole-body hyperthermia: d1, d8, q21d, rectal temperature reaches 38.5\ 39 ℃ and then maintain 1h.
Sponsors
Pengyuan Liu
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Histopathologically confirmed diagnosis of PC and clinically confirmed diagnosis of CRPC; * Complete and reliable medical history and medical records; * No other primary tumors except CRPC; * Blood tests, liver function, renal function and electrocardiogram are basically normal; * Patients with ECOG score 0\ 3, aged ≥18 years and \<90 years old; * Patients with good compliance, able to accept regular follow-up.
Exclusion criteria
* History of malignant tumor other than PC within the past 5 years; * Severe abnormalities in the patient's laboratory indices may jeopardize patient safety or compromise this study; * Accompanied by severe underlying diseases that cannot tolerate this therapy; * With acute diseases, such as acute infection, active bleeding; * Those who have recently participated in other clinical trials and have not passed the washout period; * Those who cannot tolerate systemic heat stress, such as claustrophobic patients; * Those who have a history of allergy to the drugs used in the trial; * Patients with other reasons for not being able to be enrolled in the study, according to the study doctor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biochemical objective response rate (BORR) | 3 weeks | Detect blood PSA levels before and during treatment, compare baseline and post treatment PSA difference levels, and evaluate efficacy. Bio Complete Response (BCR): PSA remains normal or decreases to normal (4ng/mL) for at least 3 weeks. Partial Biochemical Response (BPR): PSA decreased by ≥ 50% from baseline and maintained for at least 3 weeks. BPRR=BCR+BPR/All patients × 100%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bio-Disease Control Rate （BDCR） | 3 weeks | Bio Complete Response (BCR): PSA remains normal or decreases to normal (4ng/mL) for at least 3 weeks. Partial Biochemical Response (BPR): PSA decreased by ≥ 50% from baseline and maintained for at least 3 weeks. Bio Progression Disease (BPD): PSA increased by ≥ 25% from baseline. BDCR=BCR+BPR+BPD/All patients × 100%. |
Countries
China
Contacts
Primary ContactPengyuan Liu
Outcome results
None listed