An Open, Dose-escalation Clinical Study of Chimeric Exosomal Tumor Vaccines for Recurrent or Metastatic Bladder Cancer

1. Based on the applicant's previous work and combined with the clinical medical resources of our unit, tumor cells were isolated from the lesion site of cancer patients, dendritic cells or macrophages were isolated from peripheral blood, and personalized chimeric exosome vaccine was prepared for patients.
2. To evaluate the safety and tolerability of multiple administration of chimeric exosome vaccine in subjects with hatching or metastatic bladder cancer, explore the maximum tolerated dose (MDT) and dose-limiting toxicity (DLT) in humans, and recommend the safe dose range for the subsequent extended trials and subsequent clinical studies of this product.
3. To reveal the "double-effect" improvement mechanism of chimeric exosome vaccine on the activation of immune response and the microenvironment of bladder cancer lesions, improve the anti-recurrence treatment effect of bladder cancer, and realize the clinical transformation of "double-target and double-effect" chimeric exosome vaccine in the field of individualized precision treatment of bladder cancer patients.
4. To explore the clinical application value of this tumor therapeutic vaccine by using the T-cell receptor immunoomics and immunomolecular evaluation technology platform established by previous researchers, and to provide preliminary clinical research results for further vaccine development.

Study Overview

• Status: Recruiting
• Conditions: Recurrent or Metastatic Bladder Cancer
• Intervention / Treatment: Biological: Chimeric exosomal tumor vaccines

• Study Type: Interventional
• Enrollment (Anticipated): 9
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jun Ren; Phone Number: 13911568563; Email: jun.ren@duke.edu

Study Locations

• China
  • Shanghai, China, 201399
    • Recruiting
    • Fudan University Pudong Medical Center
    • Contact: Jun Ren; Phone Number: 13911568563; Email: jun.ren@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with bladder cancer confirmed by histopathology and/or cytology;
2. Age ≥18 years old and ≤85 years old, both sexes;
3. ECOG score of general physical condition 0 ~ 2 points;
4. The expected survival time is at least 3 months.
5. Lack of conventional effective treatment, failure or recurrence after conventional treatment (surgery, chemotherapy, radiotherapy, immune checkpoint inhibitors, targeted therapy, etc.), or refusal of conventional treatment;
6. According to RECIST criteria, at least one measurable objective tumor index (target lesion ≥10mm detected by spiral CT);
7. At baseline, WBC≥3.5×109/L, Hb≥90g/L, PLT≥80×109/L;

8. Subjects must have adequate organ function and the following laboratory tests during the screening period must be met:

   A) Absolute neutrophil count (ANC)≥1.5×109 /L, platelet (PLT)≥ 80×109 /L, hemoglobin (Hb)≥ 85g/L;

   B) Serum creatinine (Cr) and blood urea nitrogen (BUN) within 1.5 times the upper limit of normal values;

   C) Serum total bilirubin (TBIL) ≤ 2 times of the upper limit of normal;

   D) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times of the upper limit of normal values; Subjects with liver metastases were no more than 5 times the upper limit of normal;

   E) Activated partial thromboplastin time (APTT) and prothrombin time (PT) were within 1.5 times of the upper limit of normal values;

9. Eligible fertile patients (male and female) must consent to use a reliable contraceptive method (hormonal or barrier or abstinence) with their partner during the trial and for at least 180 days after the last dose; Women of childbearing age must have a negative urinary pregnancy test within 7 days before enrollment;
10. Subject signed informed consent voluntarily and expected compliance was good.

Exclusion Criteria:

1. Severe infection and other serious complications;
2. The patient has a previous or current primary malignancy associated with other sites, excluding effectively treated non-malignant melanoma skin cancer, carcinoma in situ of the cervix, or other malignancy that has been potentially curable with effective treatment and has been in remission for at least 5 years;
3. Patients with a history of autoimmune diseases, including but not limited to multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, scleroderma, but not vitiligo;
4. Patients with systemic corticosteroid or other immunosuppressive hormone therapy can be treated with prednisone < 0.5 mg/kg/day (maximum cell number group 40 mg/day) or other similar drugs in the equivalent cell number group, inhaled corticosteroid hormones can be used for chronic obstructive pulmonary disease (COPD) or topical use
5. Patients who have undergone major organ transplants;
6. Patients with active bleeding or severe coagulopathy;
7. Patients with active pulmonary tuberculosis and strong positive OT test;
8. Patients with previous severe interstitial lung changes (as determined by the investigator);

9. Subjects with any severe and/or uncontrolled disease, including:

   A) poor control of hyperbole (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥100mmHg);

   B) Patients with grade I or higher myocardial ischemia or infarction, arrhythmias (including QTc≥ 450ms in men and QTc≥470ms in women), and congestive heart failure grade ≥2 (NYHA classification);

   C) Active or uncontrolled severe infection (≥CTCAE grade 2 infection);

   D) Patients with previous organ transplantation, bone marrow transplantation (hematopoietic stem cell transplantation) and severe immune deficiency;

   E) Urine routine indicated urinary protein ≥++, and confirmed 24-hour urinary protein quantification > 1.0 g;

10. Four weeks before the first drug administration, antitumor therapy was performed, including endocrine, chemotherapy, radiotherapy, targeted therapy, immunotherapy and antitumor Chinese medicine therapy; For subjects receiving nitrolurea and mitomycin chemotherapy, discontinuation was within 6 weeks;
11. Had received a prophylactic or attenuated or therapeutic vaccine within 4 weeks before the first dose;
12. Toxicity after previous antitumor therapy has not recovered to CTCAE 5.0 grade 0 or level 1;
13. Current active hepatitis B, active hepatitis C, immunodeficiency virus, or other active infection of clinical significance;
14. Patients who had undergone tertiary surgery or unhealed surgical wounds 4 weeks before enrollment;
15. Participated in other clinical trials within four weeks before enrollment;
16. Pregnant or lactating women and those who plan to give birth within six months (male or female);
17. In the judgment of the investigator, the subject is not suitable to participate in the trial for any reason -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment of recurrent or metastatic bladder cancer; Lack of conventional effective treatment, failure or recurrence of treatment with conventional methods (surgery, chemotherapy, radiotherapy, immune checkpoint inhibitors, targeted therapy, etc.), or refusal of conventional treatment

Biological: Chimeric exosomal tumor vaccines; Tumor cells (lesion site) were isolated from bladder cancer patients, and bladder cancer nuclei were extracted. Monocytes were isolated from peripheral blood of this patient and induced in vitro to obtain APC (DC or macrophage). Apc-tumor chimeric cells were constructed and stimulated with immune stimulator. Chimeric exosomal vaccines were extracted from cell supernatants by differential and hypervelocity centrifugation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safty(adverse events)	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	12 months
Clinical response rate	The percentage of patients with CR and PR in the total number of patients in the same period	24 months
Overall survival(OS)	From the starting date of the enrollment until the date of the first documented disease progression or the date of the death from any cause,whichever comes first	24 months

Collaborators and Investigators

• Sponsor: Shanghai Pudong Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: September 26, 2022
• First Submitted That Met QC Criteria: September 26, 2022
• First Posted (Actual): September 29, 2022

Study Record Updates

• Last Update Posted (Actual): September 29, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Disease Attributes; Recurrence; Urinary Bladder Neoplasms
• Other Study ID Numbers: FDZJ-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No