MUC1 Therapeutic Tumor Vaccine in Advanced Solid Cancers

NCT05986981 | Unknown Phase 2

• 1 other identifier: PekingUMCHVaccineMUC1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-initiated, single-center, open, single-arm, exploratory study of a therapeutic cancer vaccine for the treatment of advanced solid tumors. A dose-escalation trial is being conducted in subjects diagnosed with advanced solid tumors to evaluate the safety and tolerability of the cancer vaccine in subjects with advanced solid tumors and to preliminarily evaluate the efficacy of the tumor vaccine in subjects with advanced solid tumors.

Conditions

Solid Tumor, Adult

Keywords

vaccine; Mucin 1; MUC1; malignant tumor

Outcome Measures

Primary Outcomes (3)

• The safety of the vaccine using CTCAE v5.0 based on the number of patients with treatment-related adverse events.

  Assess the safety of the vaccine using CTCAE v5.0 based on the number of patients with treatment-related adverse events.

  8~12weeks

• DLT

  Inject 0.5 to 2.0 mg of vaccine intramuscularly over a 16-week cycle to determine dose-limiting toxicity (DLT).

  8~12weeks

• RP2D

  Determine if the maximum tolerated dose is among the doses explored and determine the recommended phase 2 dose (RP2D) of the vaccine.

  8~12weeks

Secondary Outcomes (1)

• Preliminary assessment of the effectiveness of therapeutic oncology vaccines in advanced solid tumors.

  2years

Study Arms (1)

MUC1 Vaccine

EXPERIMENTAL

Enrollment by cohort from the starting dose of the trial and proceed to the next higher dose level if no one of the first 3 subjects develops DLT. If 1 of the 3 subjects develops DLT, then 3 additional subjects will be added to that dose level for a total of 6 subjects. If only 1 of 6 subjects develops DLT, proceed to the next higher dose level. If no fewer than 2 of the 6 subjects develop DLT, no more subjects will be added to that dose level and dose escalation will cease. The Safety Monitoring Committee (SMC) decides whether to use the intermediate dose as the next dose level for the study. Until the maximum sample size specified in the protocol or the SMC decides to terminate the dose increment.each subject receives only one dose group of study drug (during the incremental period, subjects may receive a reduced dose to continue treatment after the investigator has assessed the risk-benefit for safety reasons; dose increments are not permitted for the same subject).

Drug: Vaccine

Interventions

Vaccine DRUG

Dose-escalation trial, according to the classic "3+3" model, divided into three dose levels of 0.5 mg, 1.0 mg, 2.0 mg for enrollment, is expected to enroll a total of 9-18 subjects (0.5 mg dose group to be enrolled in 3-6 subjects, 1.0 mg dose group is proposed to be enrolled in 3-6 subjects, 2.0 mg dose group is proposed to be enrolled in 3-6 subjects, and the dose group is proposed to be enrolled in 3-6 subjects, and the dose group is proposed to be enrolled in 3-6 subjects. dose group is proposed to include 3-6 subjects).

MUC1 Vaccine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• screening period patients are able to understand and voluntarily sign an informed consent form;
• males and females between the ages of 18 and 75 years (both ends included);
• expected survival ≥ 3 months;
• advanced subjects with histologically or cytologically proven advanced solid tumors who have failed standard multiline therapy;
• have at least one measurable lesion (i.e., mass ≥10 mm in diameter and malignant lymph node ≥15 mm in short diameter on enhanced scan with layer thickness ≤5 mm on spiral CT) according to the efficacy evaluation criteria for solid tumors, RECIST version 1.1 (see Appendix 4, Criteria for Evaluating the Efficacy of Solid Tumor Treatments);
• Fresh or archived tumor tissue samples within 5 years are available for central laboratory testing during the screening period (if they are truly unavailable, this will not affect enrollment);
• ECOG physical status score of 0 to 2;
• treatment with other anti-tumor drugs (e.g., chemotherapy, hormone therapy, immunotherapy, antibody therapy, radiotherapy) prior to the first dose exceeds the 5 half-life of the drug or more than 4 weeks before the first dose (whichever is shorter);
• Organ function levels must meet the following requirements (no blood or blood product transfusion, hematopoietic stimulating factor, albumin, or blood product use within 14 days prior to the examination): absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥ 75 × 109/L, hemoglobin (Hb) ≥ 90 g/L; serum total bilirubin (TBIL) ≤ 1.5 Total bilirubin (TBIL) ≤1.5 times the upper limit of normal value, glutamic transaminase (AST) and alanine aminotransferase (ALT) ≤2.5 times the upper limit of normal value (if liver metastasis is present, total bilirubin ≤3 times the upper limit of normal value, AST and ALT ≤5 times the upper limit of normal value are allowed). 10;
• Pre-menopausal women of childbearing potential must undergo a pregnancy test within 7 days prior to the start of treatment, and the result of the pregnancy test must be negative and non-lactating; women without childbearing potential may not undergo a pregnancy test and contraception, provided they are over 50 years of age, have not used hormone therapy and have stopped menstruating for at least 12 months, or have been sterilized. All enrolled subjects (either male or female) should use adequate barrier contraception throughout the treatment period and for 3 months after completion of treatment.
• Other toxicity parameters must be NCI-CTCAE v.5.0 Grade 0 or 1.

You may not qualify if:

• Subjects who require long-term systemic application of anti-allergic medications or who have a history of life-threatening allergic reactions to any vaccine or medication;
• those with symptomatic or rapidly progressing central system metastases. Presence of extensive pulmonary metastases causing respiratory distress; subjects with tumours in close proximity to or invading large blood vessels or nerves;
• new cerebrovascular accidents (including ischaemic stroke, haemorrhagic stroke and transient ischaemic attack) within 6 months prior to screening;
• acute myocardial infarction, uncontrolled angina pectoris, uncontrolled arrhythmia, severe heart failure (see Appendix 3, New York Heart Association's Heart Failure Classification Criteria, NYHA Class ≥ III) and other cardiovascular diseases within 6 months prior to screening;
• have received immunomodulatory medications within 4 weeks prior to the date of first vaccination (D1), including, but not limited to, IL-2, CTLA-4 inhibitors, CD40 agonists, CD137 agonists, and IFN-alpha (except for high-risk surgical subjects using IFN-alpha as an adjuvant therapy if IFN-alpha therapy was discontinued within the 4 weeks prior to the date of the trial);
• those with a history of renal insufficiency with serum creatinine levels greater than 1.5 times the upper limit of normal;
• have received a blood transfusion, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 2 weeks prior to the first dose of drug;
• subjects with skin conditions that may prevent intradermal vaccine from reaching the target area (e.g., psoriasis);
• subjects in the Screening Period who continue to have adverse reactions from prior anti-neoplastic therapy that have not been restored to a CTCAE Version 5.0 grade rating of ≤ Grade 1 (with the exception of alopecia and platinum-induced neurotoxicity of ≤ Grade 2);
• need for concomitant use of steroidal hormonal medications (tumour or non-tumour related disease); exceptions may be made for those requiring topical (not applied to the vaccination site) or inhaled steroids;
• the presence of active or uncontrollable infections requiring systemic therapy (except for simple urinary tract infections or upper respiratory tract infections) in the subject within 4 weeks prior to screening; and the presence of antibodies to the Human Immunodeficiency Virus (HIV), hepatitis B Surface Antigen (SAB) positive and/or hepatitis B Core Antibody (HBCO) positive with Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) \>1000 copies/mL and Hepatitis C virus (HCV) antibodies on virological testing during the Screening Period, Subjects who are positive for antibodies specific to syphilis spirochetes;
• poorly controlled hypertension (defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg) after treatment;
• subjects with a history of autoimmune disease \[e.g., the following, but not limited to: interstitial pneumonitis, uveitis, enteritis, hepatitis, pituitary gland inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism (hypothyroidism without clinical symptoms or hypothyroidism due to radiotherapy may be included), subjects with vitiligo or cured asthma that does not currently require any intervention may be included, subjects requiring bronchodilators for medical intervention cannot be included\];
• subjects with active ulcers or gastrointestinal bleeding during the Screening Period;
• subjects who have received a previous similar therapeutic cancer vaccine or who have received another vaccine within 4 weeks prior to Screening;

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

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MeSH Terms

Conditions

Medullary cystic kidney disease 1; Neoplasms

Interventions

Vaccines

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Central Study Contacts

Fang Li, MD

CONTACT

+86-010-69154417; lifang@pumch.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study flow included a screening period (week -4 to day -1), a treatment period (day 1 to week 8 or 16, including a DLT observation period on days 1-28), an end-of-treatment visit, and a survival follow-up. The treatment period included the initial treatment period (day 1 to week 8) and the augmentation period (week 12 to week 16). Subjects after signing and providing formal informed consent entered the screening period, during which eight separate administrations of the vaccine were administered, of which the investigator determined whether to continue treatment from week 8 to week 12 based on a combination of efficacy, safety, and adherence.

Study Record Dates

• First Submitted: May 4, 2023
• First Posted: August 14, 2023
• Study Start: August 1, 2023
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: August 14, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)