TQB3616 Capsules Combined With Abiraterone Acetate Plus Prednisone in Metastatic Castration-Resistant Prostate Cancer

NCT05156450 | Unknown Phase 2

• 1 other identifier: NMPA 2018L02262/2018L02263
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase Ib/II clinical study of TQB3616 capsules in combination with abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer, to determine the dose for further clinical studies and to evaluate the safety and efficacy of this combined therapy.

Conditions

Prostatic Neoplasms, Castration-Resistant; Drug Therapy, Combination

Outcome Measures

Primary Outcomes (1)

• 12-month radiographic progression-free survival (rPFS) rate

  Percentage of subjects with radiographic progression-free survival of 12 months or more

  12 months

Secondary Outcomes (8)

• rPFS

  2 years

• 6-month rPFS rate

  6 months

• Prostate specific antigen (PSA) response rate

  2 years

• Time to PSA progression

  2 years

• Objective response rate (ORR)

  2 years

Other Outcomes (1)

• Biomarkers related to efficacy, mechanism of action, safety, and/or pathogenesis, such as cell cycle pathway-related genes

  2 years

Study Arms (1)

Dose Extension

EXPERIMENTAL

At the recommended phase II dose of TQB3616 combined with abiraterone acetate (1000 mg, q.d.) plus prednisone (5 mg, b.i.d.), 20-40 patients are planned to be enrolled to evaluate the efficacy and safety of the combination therapy. Metastatic and genomic tests based on tissue biopsy samples (primary or metastatic) and blood samples will be performed before treatment and after disease progression.

Drug: TQB3616 Capsules Combined With Abiraterone Acetate Plus Prednisone

Interventions

TQB3616 Capsules Combined With Abiraterone Acetate Plus Prednisone DRUG

Treatment with TQB3616 in combination with abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer.

Dose Extension

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male patients ≥ 18 years old and ≤ 80 years old (based on the date of signed informed consent); willing and able to provide written informed consent and good compliance.
• Histologically or cytologically confirmed prostatic adenocarcinoma. Patients with small cell or large cell neuroendocrine carcinoma, prostatic uroepithelial carcinoma, basal cell carcinoma, sarcomatoid carcinoma, carcinoid carcinoma and ductal adenocarcinoma are excluded.
• Imaging (e.g. bone scan and CT/MRI) confirmed metastatic disease.
• Serum testosterone level ≤ 1.73 nmol/L (50 ng/dL) at the screening visit. Patients who did not undergo bilateral orchiectomy required continued treatment with androgen deprivation therapy (ADT) \[gonadotropin-releasing hormone analogue (LHRHa, agonist/antagonist)\] throughout the study period.
• At least two consecutive elevated PSA values separated by at least 1 week, and if elevated PSA is determined to be the only evidence of progression, the last result must be at least 1.0 ng/mL. Patients receiving anti-androgen therapy must have experienced PSA progression after discontinuation (≥4 weeks since last flutamide administration or ≥6 weeks since last bicalutamide or nilumet).
• Disease progression as assessed by RECIST 1.1, regardless of the presence of PSA progression.
• Skeletal disease progression as assessed by PCWG3, i.e. ≥ 2 new lesions found on bone scan and re-evaluated at least 8 weeks later with ≥ 2 new lesions other than the last evaluated new bone lesions, regardless of the presence of PSA progression.
• Patients must have discontinued all prior cancer therapy (except ADT and bone loss prophylaxis) and have recovered to ≤ Grade 1 or baseline (according to the Common Terminology Criteria for Adverse Events version 5.0 \[CTCAE v 5.0\]) from all acute toxic effects of prior therapy or surgery prior to the first dose, except alopecia and peripheral neuropathy, and the washout period since the last previous systemic or radiation therapy is as follows:
• At least 4 weeks must have elapsed from the use of 5-alpha reductase inhibitors (e.g., dutasteride, finasteride), estrogens, and cyproterone to enrollment.
• At least 4 weeks must have elapsed from the use of chemotherapy (i.e., docetaxel for metastatic hormone sensitive prostate cancer) to enrollment.
• At least 4 weeks must have elapsed between major surgery or radiation therapy and enrollment.
• Normal organ function (including blood routine, blood biochemistry, urine routine, coagulation function, thyroid function, cardiac function assessment, etc.).
• Eastern Cooperative Oncology Group (ECOG) physical status (PS) of 0 to 1. Expected survival ≥ 6 months.
• Willingness to comply with study procedures. Patients of childbearing potential must agree to use an effective method of contraception and avoid sperm donation for the duration of the study and for at least 3 months after the last study treatment dose.

You may not qualify if:

• Those who present any of the following criteria will not be enrolled in this trial.
• Tumor disease and medical history.
• Subjects with brain metastases with symptoms or symptom control for less than 1 month, unless signs and/or symptoms of central nervous system (CNS) involvement are present, screening for CNS metastases is not required at baseline.
• Have presented within 3 years or have a current concurrent other malignancy. The following two conditions are eligible for enrollment: other malignancies treated with a single procedure to achieve 5 consecutive years of disease free generation (DFS); cured carcinoma in situ of the cervix, non-melanoma skin cancer and superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)\]; for patients with carcinoma in situ of any origin and for patients with previous malignancies currently in remission are eligible to participate in this study if, in the judgment of the investigator, the likelihood of recurrence is considered very low, and the investigator will approve these patients prior to enrollment.
• Those whose imaging (CT or MRI) shows that the tumor has invaded the vital vascular perimeter or who, in the judgment of the investigator, are at high risk of fatal hemorrhage due to tumor invasion of vital vessels during the follow-up study.
• the presence of severe bone damage caused by tumor bone metastases; or pathological fractures and spinal cord compression at important sites that have occurred within the last 6 months or are expected to be likely to occur in the near future as judged by the investigator.
• uncontrolled pleural effusion, pericardial effusion or ascites that still requires repeated drainage (in the judgment of the investigator).
• Prior antitumor or combination drug therapy.
• Use of botanicals (e.g., saw palmetto) that may lower PSA levels within 4 weeks prior to the first dose.
• Prior antineoplastic therapy less than 4 weeks from the first dose, including surgery, chemotherapy, palliative radiotherapy for non-target lesions, hormonal therapy (including first-generation AR antagonists \[e.g., flutamide, bicalutamide, nilumide\], 5α-reductase inhibitors \[e.g., finasteride\], estrogens, and cyproterone), adjuvant therapy with targeted agents, biologic therapy, cytokine immunotherapy, clinical trial drug therapy, etc.
• previous oral targeted drugs with less than 5 drug half-lives from the first dose (calculated from the end time of the last treatment)
• Prior antitumor therapy-related toxicity not recovered to Common Terminology Criteria for Adverse Events (CTCAE) ≤ grade 1, except for alopecia.
• Previous treatment with cytochrome P450 family 17 (CYP17) inhibitors (including agents such as TAK-700, TOK-001 and ketoconazole), with no restrictions for patients previously treated with abiraterone.
• Prior treatment with Abemaciclib or Palbociclib and any other CDK4/6 inhibitors.
• Patients treated with drugs known to be potent inhibitors of cytochrome P450 3A4 (CYP3A4) or potent or moderately potent inducers and unable to discontinue these drugs or switch to a different drug at least 5 half-lives prior to initiation of study drug therapy.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West China Hospital

Chengdu, Sichuan, 610000, China

Location

Related Publications (6)

• Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, Bray F. International variation in prostate cancer incidence and mortality rates. Eur Urol. 2012 Jun;61(6):1079-92. doi: 10.1016/j.eururo.2012.02.054. Epub 2012 Mar 8.

  PMID: 22424666 BACKGROUND

• Knudsen ES, Witkiewicz AK. The Strange Case of CDK4/6 Inhibitors: Mechanisms, Resistance, and Combination Strategies. Trends Cancer. 2017 Jan;3(1):39-55. doi: 10.1016/j.trecan.2016.11.006.

  PMID: 28303264 BACKGROUND

• Kase AM, Copland Iii JA, Tan W. Novel Therapeutic Strategies for CDK4/6 Inhibitors in Metastatic Castrate-Resistant Prostate Cancer. Onco Targets Ther. 2020 Oct 15;13:10499-10513. doi: 10.2147/OTT.S266085. eCollection 2020.

  PMID: 33116629 BACKGROUND

• First CDK 4/6 Inhibitor Heads to Market. Cancer Discov. 2015 Apr;5(4):339-40. doi: 10.1158/2159-8290.CD-NB2015-028. Epub 2015 Feb 23.

  PMID: 25711280 BACKGROUND

• Comstock CE, Augello MA, Goodwin JF, de Leeuw R, Schiewer MJ, Ostrander WF Jr, Burkhart RA, McClendon AK, McCue PA, Trabulsi EJ, Lallas CD, Gomella LG, Centenera MM, Brody JR, Butler LM, Tilley WD, Knudsen KE. Targeting cell cycle and hormone receptor pathways in cancer. Oncogene. 2013 Nov 28;32(48):5481-91. doi: 10.1038/onc.2013.83. Epub 2013 May 27.

  PMID: 23708653 BACKGROUND

• Frank S, Nelson P, Vasioukhin V. Recent advances in prostate cancer research: large-scale genomic analyses reveal novel driver mutations and DNA repair defects. F1000Res. 2018 Aug 2;7:F1000 Faculty Rev-1173. doi: 10.12688/f1000research.14499.1. eCollection 2018.

  PMID: 30135717 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant

Interventions

Abiraterone Acetate; Prednisone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Study Officials

• Hao Zeng

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hao Zeng, Doctor

CONTACT

8618980602129; kucaizeng@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Department of Urology

Study Record Dates

• First Submitted: November 19, 2021
• First Posted: December 14, 2021
• Study Start: January 1, 2022
• Primary Completion: October 1, 2023
• Study Completion: January 1, 2024
• Last Updated: December 14, 2021

Record last verified: 2021-12

Locations

CN (1)