Personalized Cancer Vaccine in Egyptian Cancer Patients (PROVE)

Phase I Clinical Trial of Alfa-Fetoprotein,Glypican-3 Based Personalized Cancer Vaccine in Egyptian Patients With Hepatocellular Carcinoma: Pilot Study

Evaluate safety and immunogenicity of peptide cancer vaccine in patients with hepatocellular carcinoma (HCC) who developed recurrence after surgical resection and refractory to the available institutional standard of care lines of treatment .

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Biological: Peptide cancer vaccine

Detailed Description

Ten patients with hepatocellular carcinoma (HCC) who developed recurrence after surgical resection are refractory to the available institutional standard of care lines of treatment will be recruited to received the peptide cancer vaccine.

Tumour antigen peptides will be identified and separated from each patient and then reinjected with an adjuvant (autologous activated monocytes with autologous tumour derived heat shock protein 70) by subcutaneous route monthly for 6 months preceded by 300 mg cyclophosphamide one week before start of the vaccine.

A follow up for all cases will be performed clinically, laboratorial, and immunologically for one year.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zeinab A Ashour, MD; Phone Number: 01096056735; Email: zeinabashour2012@yahoo.com
• Study Contact Backup: Name: Mai A Aldeeb, MD; Phone Number: 01020338896; Email: Mael_deeb@yahoo.com

Study Locations

• Egypt
  • Cairo, Egypt, 11566
    • Recruiting
    • Faculty of Medicine Ain Shams Research Institute- Clinical Research Center (MASRI-CRC)
    • Contact: Manal El-Sayed, MD; Email: manalhelsayed@yahoo.co.uk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients who developed recurrence of HCC after surgical resection .
2. Age ≥ 18 years.
3. Eastern Cooperative Oncology Group performance status (ECOG) of 0-2 .
4. Patient with radiologically or pathologically confirmed hepatocellular carcinoma.
5. Patients who had been treated with surgical approach as per our (Ain Shams University) institute protocols and developed recurrence after surgery. They were either intolerant to the institute protocol of treatment or showed unresponsiveness of their disease after treatment.
6. Child-Pugh class A or B .

7. LAB values:

   Hemoglobin (≥ 8 g/dl), platelets (≥ 50,000/µl), leukocytes (≥ 2,500/µl), neutrophils (≥ 1,000/µl), lymphocytes (≥ 500/µl) Liver function: serum bilirubin (< 3 x ULN), Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) (< 5 x ULN) Renal function: serum creatinine (< 1.5 x ULN)

8. Patient has not received any antineoplastic chemotherapy, immunotherapy, or radiotherapy for the four weeks prior to the start of study treatment.
9. Pregnancy test should be negative at the first dose of study treatment in fertile females. (Female patients who are not post-menopausal or surgically sterile should use a highly effective method of birth control from the date of signing the consent to the last follow up visit. Pregnancy test should be negative at the first dose of study treatment.)
10. Written informed consent .

Exclusion Criteria:

1. Patients receiving continuous systemic steroid treatment within the last 4 weeks prior to start of study treatment (The use of inhaled and nasally applied steroids, as well as topical steroids outside the vaccination area are permitted)
2. Patients receiving systemic immunotherapy or immunosuppressant medication other than steroids within the last 4 weeks prior to start of study treatment.
3. Patients with a history or evidence of systemic autoimmune disease.
4. Active second malignancy or a prior malignancy within the past 12 months.
5. Acute active infections requiring oral or intravenous antibiotics, antiviral or antifungal therapy within 1 week before the start of study treatment [Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infections are permitted; direct-acting antivirals may be administered when medically indicated].
6. Any other acute medical condition that may compromise patient's safety or the activity of the studied vaccine treatment.
7. Any other concurrent severe or uncontrolled chronic disease such as uncontrolled non-malignant liver, renal or lung disease, or decompensated cardiac failure or coronary insufficiency.
8. Administration of a live, attenuated vaccine within 4 weeks before randomization
9. Known previous major hypersensitivity reactions.
10. History of human immunodeficiency virus (HIV)
11. Evidence of current alcohol or drug abuse
12. Women who are pregnant or who are breast feeding
13. Medical or mental impairments that may limit participation in the study as judged by the investigators disease specialist.
14. History of organ allograft.
15. History of splenectomy.
16. Psychiatric illness or known social situation that would preclude study compliance.
17. Encephalopathy.

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: Experimental Personalized Cancer Vaccine; Patients with recurrent HCC after surgical resection and refractory to available line of treatment will receive Personalized peptide based vaccine with autologous heat shock protein 70 and autologous activated monocytes	Biological: Peptide cancer vaccine; Vaccine content are personalized peptides vaccine separated from each patients own tumor cells, autologous heat shock protein 70 separated from tumor cells and autologous activated monocytes that administered subcutaneously monthly for six months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the safety of the personalized cancer vaccine	Percentage of patients who developed adverse events (AEs)	4 weeks
Assessment of immunological response	Percentage of change in CD20 +B-cells, CD16+CD56+NK cells,CD4 + cells,CD8+ cells,CD25+regulatory cells	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival and overall survival time	Progression free survival (PFS) time and overall survival (OS)time will be analysed using the Kaplan-Meier estimation method and log-rank test.	144 week

Collaborators and Investigators

• Sponsor: zeinab ahmed yousif hasan ashour
• Investigators: Principal Investigator: Zeinab A Ashour, MD, Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2021
• Primary Completion (Anticipated): April 1, 2024
• Study Completion (Anticipated): August 1, 2024

Study Registration Dates

• First Submitted: May 11, 2021
• First Submitted That Met QC Criteria: September 16, 2021
• First Posted (Actual): September 28, 2021

Study Record Updates

• Last Update Posted (Actual): August 11, 2022
• Last Update Submitted That Met QC Criteria: August 10, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Peptide vaccine, Heat shock protein 70, Monocytes
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: FMASU P109g/2019-2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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