Gene Therapy for Cancer Recurrence

Recruiting at 1 trial location

Overseen By Kunju Sridhar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Systemic SCC treatments

Disqualifiers: Pregnancy, Metastatic SCC, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

16 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on any current systemic treatment for squamous cell carcinoma (SCC).

What data supports the effectiveness of the drug BVEC for cancer recurrence?

Bevacizumab, a component of BVEC, has shown effectiveness in improving survival and quality of life in patients with recurrent glioblastoma and non-small-cell lung cancer. It works by blocking a protein that helps tumors grow new blood vessels, which can slow down cancer progression. ^{1 2 3 4 5}

Is gene therapy generally safe for humans?

Gene therapy has been studied in various conditions, including cancer, and generally shows an acceptable safety profile. Some side effects like fever and changes in blood markers have been noted, but no deaths or new cancers were linked to the therapy. Retroviral vectors used in gene therapy have not shown evidence of replication issues, supporting their safety. ^{6 7 8 9 10}

How does the treatment BVEC differ from other treatments for cancer recurrence?

BVEC is unique because it involves gene therapy, which aims to treat cancer recurrence by altering genes within the body, potentially offering a novel approach compared to traditional treatments like chemotherapy or surgery. This method may target the underlying genetic causes of cancer, providing a different mechanism of action. ^{3 11 12 13 14}

What is the purpose of this trial?

The study objective is to see if BVEC induced C7 expression in Recessive Dystrophic Epidermolysis Bullosa (RDEB) skin following Squamous cell carcinoma (SCC) excision will normalize the invasive tumor microenvironment and reduce tumor recurrence. Prevention of SCC's in the RDEB subjects will increase their life span.

Research Team

M. Peter Marinkovich, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for individuals with Recessive Dystrophic Epidermolysis Bullosa (RDEB) who have had Squamous Cell Carcinoma (SCC) removed. It aims to see if a gene therapy can prevent cancer from coming back and improve life expectancy.

Inclusion Criteria

I have been diagnosed with RDEB due to COL7A1 mutations.

My cancer is confirmed as squamous cell carcinoma.

Ability to understand and the willingness to provide written informed consent

Exclusion Criteria

Subject is pregnant

I cannot travel to the study site for visits.

I have metastatic squamous cell carcinoma or am currently on treatment for it.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

BVEC induced C7 expression is applied to RDEB skin following SCC excision to reduce tumor recurrence

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• BVEC

Trial Overview The intervention being tested is BVEC, a gene therapy designed to express the COL7A1 gene in RDEB skin after SCC excision, potentially reducing tumor recurrence by normalizing the tumor environment.

Participant Groups

Group I: Treatment with BVEC Active Control 1 Intervention

Group II: No treatment with BVEC Active Control 1 Intervention

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Epidermolysis Bullosa Research Partnership

Collaborator

Trials

4

Recruited

80+

Epidermolysis Bullosa Research Partnership

Collaborator

Trials

5

Recruited

90+

Findings from Research

In a retrospective analysis of 217 patients from the ECOG 4599 study, those who received bevacizumab (BV) maintenance therapy after induction treatment showed significantly longer progression-free survival (4.4 months) compared to those who received carboplatin and paclitaxel (CP) alone (2.8 months).

The safety profile of BV maintenance was favorable, with less than 1% of patients experiencing severe hematological toxicities and no severe nausea, vomiting, or diarrhea, indicating that BV can be a safe option for maintaining treatment benefits in non-small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab maintenance in patients with advanced non-small-cell lung cancer, clinical patterns, and outcomes in the Eastern Cooperative Oncology Group 4599 Study: results of an exploratory analysis. Lopez-Chavez, A., Young, T., Fages, S., et al.[2015]

In a study involving 737 patients across 60 clinical trials, no evidence of replication competent retrovirus (RCR) was found in 1,595 post-treatment blood samples, supporting the safety of gammaretroviral vectors used in gene therapy.

The majority of the trials (93%) focused on cancer immunotherapy, and the results indicate that current manufacturing methods effectively produce RCR-free products, reinforcing the overall safety profile of retroviral gene therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Replication competent retrovirus testing (RCR) in the National Gene Vector Biorepository: No evidence of RCR in 1,595 post-treatment peripheral blood samples obtained from 60 clinical trials. Cornetta, K., Yao, J., House, K., et al.[2023]

Engineered T cell therapies, like CAR T cells and TCR T cell therapies, have shown remarkable efficacy in treating certain blood cancers, highlighting their potential as a powerful tool in cancer immunotherapy.

However, these therapies also pose unique safety challenges, such as cytokine release syndrome and neurotoxicity, which require careful nonclinical safety assessments to ensure patient safety during development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical safety assessment of engineered T cell therapies. Lebrec, H., Maier, CC., Maki, K., et al.[2022]

Bevacizumab (BEV) has shown a median radiographic response rate of 25% and a 6-month progression-free survival (PFS6) rate of 40% in patients with recurrent glioblastoma, leading to its accelerated approval in the USA for this indication.

Despite improvements in treatment options, glioblastoma remains a challenging and incurable condition, with current therapies yielding low response rates and variable survival outcomes, highlighting the need for ongoing research into effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab for the treatment of glioblastoma. Chowdhary, S., Chamberlain, M.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Bevacizumab maintenance in patients with advanced non-small-cell lung cancer, clinical patterns, and outcomes in the Eastern Cooperative Oncology Group 4599 Study: results of an exploratory analysis. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Dual VEGF inhibition with sorafenib and bevacizumab as salvage therapy in metastatic colorectal cancer: results of the phase II North Central Cancer Treatment Group study N054C (Alliance). [2022]

3. United States pubmed.ncbi.nlm.nih.gov

A predictive value of von Willebrand factor for early response to Bevacizumab therapy in recurrent glioma. [2019]

4. Egypt pubmed.ncbi.nlm.nih.gov

Bevacizumab improves quality of life in patients with recurrent glioblastoma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Long-Term Safety Follow-Up of Subjects Previously Treated with Non-Replicating Retroviral Vector-Based Gene Therapies. [2018]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Safety profile of plasmid/liposomes and virus vectors in clinical gene therapy. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of gene therapy viral vectors. [2009]

9. United States pubmed.ncbi.nlm.nih.gov

Replication competent retrovirus testing (RCR) in the National Gene Vector Biorepository: No evidence of RCR in 1,595 post-treatment peripheral blood samples obtained from 60 clinical trials. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Nonclinical safety assessment of engineered T cell therapies. [2022]

11. China pubmed.ncbi.nlm.nih.gov

[Experimental BCSC-1 gene therapy on nasopharyngeal carcinoma mediated by adenovirus]. [2012]

12. England pubmed.ncbi.nlm.nih.gov

Bevacizumab for the treatment of glioblastoma. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Human endostatin gene transfer, either naked or with liposome, has the same inhibitory effect on growth of mouse liver tumor cells in vivo. [2019]

14. Greece pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bevacizumab for the treatment of glioblastoma. [2020]