Her1 vaccine in metastatic colon and prostate cancer

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General information

Section to complete general information about the trial: scientific and public title, protocol identifiers, sponsors and Source(s) of Monetary or Material Support.

Scientific title:

Phase I/II study with the HER1 therapeutic vaccine in patients with asymptomatic or minimally symptomatic hormonal castration-resistant prostate cancer or metastatic colon cancer.

Secondary indentifying numbers:

Not applicable

Issuing authority of the secondary identifying numbers:

Not applicable

Source(s) of monetary or material support:

Center of Molecular Immunology (CIM), Ministry of Public Health (MINSAP)

Authorization for beginning

Section to complete information about the regulatory approval of clinical trial: regulatory agency name, approval date and reference number in the agency.

Regulatory instance to authorize the initiation of the study:

Center for State Control of Drugs, Medical Devices and Equipment (CECMED)

Reference number:

In process

Principal investigator

Section to complete information about Email address, telephone number and postal address of the Principal Investigator.

First name:

Iraida

Last name:

Caballero Aguirrechu

Medical Specialty :

2nd degree specialist in Oncology

Affiliation:

Hermanos Ameijeiras Hospital

Postal address:

San Lazaro 701 and Belascoain, Centro Habana

City:

Havana

País:

Cuba

Zip Code:

10300

Telephone:

+53-78761436

Email address:

iraida.caballero@infomed.sld.cu

Clinical sites to participate

Section to complete the data related to the clinical sites involved in the trial: site and responsible investigator for every site.

Countries of recruitment:

Cuba

Clinical sites:

Not applicable

Recruitment status

Section to complete information about the recruitment status and the date of first enrolment subject

Recruitment status:

Pending

Date of first enrollment:

02/11/2023

Health condition and Intervention

Section to complete information about the primary medical condition(s) or problem(s) studied and, a characteristics of the intervention(s).

Health condition(s) or Problem(s) studied:

prostate and colon cancer

Health condition(s) code:

Prostatic Neoplasms, Castration-Resistant

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Prostatic Diseases

Genital Diseases, Male

Male Urogenital Diseases

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Colonic Diseases

Intestinal Diseases

Gastrointestinal Diseases

Digestive System Diseases

Intervention(s):

All patients included in the study will be treated with the HER1 vaccine. Dose: Initially 2 dose levels (400µg and 800µg) will be opened in each stratum (prostate and colon). In the event of closure of both dose levels due to some stop criteria, another dose (1200 µg) will be opened. Route of administration: Intramuscular. Treatment frequency: Every 14 days during the first five administrations (approximately 2 months) and subsequently, every 28 days for the remaining ten immunizations, until discontinuation for any of the reasons provided for in the research protocol or upon completion of 12 months of treatment. . The treatment period will be 336 days, approximately 12 months.

Intervention code:

ErbB Receptors

Vaccines

Injections, Intramuscular

Intervention keyword:

HER1, therapeutic vaccine

Outcomes and Timepoint

Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.

Primary outcome(s):

Proportion of patients with serious adverse events with a causal relationship (according to CTCAE criteria and causality criteria: SAE with very probable, probable or possible causation). Measurement time: at all times of administration of the research product.

Key secondary outcomes:

- Proportion of patients with neutralizing antibody levels. will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Recognition of the human vulvar tumor line A431. will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Response of IFN γ-producing T cells. It will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Frequency of myeloid suppressor cells (MDSC). will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Frequency and absolute number of T cells (CD4; CD8; Tregs and NK) (flow cytometry). will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Measurement of EGF in serum. will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Inhibition of the ligand (EGF)-HER1 receptor interaction by binding the antibodies generated with the HER1 vaccine in human tumor lines (flow cytometry). will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 Inhibition of HER1 phosphorylation. will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Effect of treatment on the expression of PDL1 and MHC-I. will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Induction of markers of apoptosis such as phosphatidyl serine and DNA fragmentation. will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Dissemination of the antigenic response of the antibodies induced by the treatment (Wester blot, ELISA, Protoarray). will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Cytokines secreted by T cells (ELISA). will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Evaluate the prognostic value of systemic inflammatory indices (NLR, PLR, MRL). The ratio between neutrophils, lymphocytes, platelets and monocytes will be measured, from a complete blood count with differential and a platelet count. It will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Expression of PD1L in the tumor sample (IHC). will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Serum levels of proinflammatory cytokines: IL6, IL8 (ELISA). will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Serum levels of soluble HER1 and EGF. will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Microsatellite instability and Kras for patients with colon cancer. will measure on days 0, 56, 84, 112, 140, 196, 252, 336 - Determine DNA fragments in liquid biopsy. will be measured on days 0, 56, 84, 112, 140, 196, 252, 336 - Toxicity (Occurrence of any AE, description, duration, intensity, severity, result, attitude towards treatment, causal relationship, treatment indicated for the AE) - Results of laboratory tests (hematological, hemochemical and urine). it will be measured prior to inclusion and then every 28 days from immunization 0 until the final evaluation (4 weeks after the last immunization) - Vital signs (blood pressure (BP), heart rate (HR), temperature) Vaccine lot. it will be collected with each administration of the product. will be measured at baseline and during treatment (with each immunization) - Objective response (according to RECIST criteria:). it will be measured at months 3, 6, 9, and 4 weeks after the last dose. - Progression-free survival (time elapsed from the start of treatment to the date the disease progresses) - Overall survival (time elapsed from the inclusion of the patient in the study until the patient's death) - Quality of life (It will be measured by the QLQ-PR25 survey in patients with prostate cancer, and the QLQ-CR29 survey in patients with colon cancer). They will be applied prior to the start of immunizations (day 0), at month 6 and at the end of treatment.

Selection criterias

Section to complete information about the inclusion and exclusion criteria for participant selection, including age and gender.

Gender:

Male/Female

Minimum age:

19 years

Maximum age:

None

Inclusion criteria:

1. Compliance with one of the two diagnostic criteria defined for each disease (CPRC, CCM). 2. Patient who gives their informed consent to participate in writing. 3. Age over 18 years. 3. General condition according to ECOG ≤ 2. 4. Life expectancy of at least 6 months. 5. Organ and bone marrow function defined by the following parameters: - Hemoglobin (Hb) ≥ 9 g/dl, - Total leukocyte count ≥ 3 x 109/L, - Platelet count (PC) ≥ 100 x 109/L , - Total bilirubin and/or Alkaline Phosphatase ≤ 2.5 times the institutional upper normal limit.

Exclusion criteria:

1. Patients of childbearing age who are not using an adequate method of contraception (intrauterine devices, hormonal contraceptives, barrier methods or surgical sterilization) prior to their inclusion in the study. 2. Pregnant or lactating. 3. Known positive serology for HIV, hepatitis B or C. 4. Decompensated allergic states or history of severe allergic reactions. 5. Acute or chronic decompensated lung diseases. 6. Previous history of demyelinating or inflammatory diseases of the central (CNS) or peripheral (PNS) nervous system. 7. Uncontrolled intercurrent illnesses including, but not limited to: active infections, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, Diabetes Mellitus and/or psychiatric illness involving the incompetence of the subject. 8. Brain metastasis. 9. Known hypersensitivity to any component of the formulation. 10. Patients who are receiving another investigational product.

Type of population:

Adults

Type of participant:

Patients

Study design

Section to complete information about the characteristics of the study design.

Type study:

Interventional

Purpose:

Treatment

Allocation:

N/A: single arm study

Masking:

Open

Control group:

Uncontrolled

Study design:

Single group

Phase:

1-2

Target sample size:

88

Contact for public queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status

First Name:

Lisania

Last Name:

Reyes Espinosa

Specialty:

1st degree specialist in Immunology

Affiliation:

Center of Molecular Immunology (CIM)

Postal Address:

216 and 15, Atabaey, Playa

City:

Havana

País:

Cuba

Zip Code:

11600

Telephone:

+53-72717933 ext 3489

Email :

lisania@cim.sld.cu

Contact for scientific queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to scientific queries.

First Name:

Belinda

Last Name:

Sánchez Ramírez

Specialty:

Degree in Biochemistry, Biological PhD

Affiliation:

Center of Molecular Immnulogy (CIM)

Postal Address:

216 & 15, Atabey, Playa

City:

Havana

País:

Cuba

Zip Code:

11600

Telephone:

+53-72717933 ext 3168

Email :

belinda@cim.sld.cu

Research Ethics Committees

Section to complete the data related to the review ethics committees.

Name of Research Ethics Committees:

Hermanos Ameijeiras Surgical Clinical Hospital (HHA)

Status of evaluation:

Approved

Status of evaluation date of Ethic Committee:

16/09/2022

Postal address of Ethic Committee :

San Lazaro 701 esq. Belascoain, Centro Habana, Havana, Cuba, ZC 10400

Telephone:

+53-78761000

Correo electrónico:

hha@infomed.sld.cu

About study completion

Section to complete the data related to the study completion.

Study completion date:

03/11/2025

Registration and Update

Section to complete information about the name of Primary Registry, date of registration and the unique ID number assigned by the registry (RPCEC).

Primary registry:

RPCEC

Unique ID number:

RPCEC00000431

Date of Registration in Primary Registry:

16/08/2023

Record Verification Date:

2023/08/16

Next update date:

2024/08/16

Link to the spanish version:

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Ensayos Registrados

Proceso de Registro

Her1 vaccine in metastatic colon and prostate cancer

Acerca del RPCEC

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