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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a gene therapy called BVEC can prevent skin cancer from recurring in individuals with Recessive Dystrophic Epidermolysis Bullosa (RDEB). Researchers aim to determine if applying BVEC after removing squamous cell carcinoma (SCC) can create a skin environment less conducive to cancer's return. The trial includes two groups: one receiving BVEC treatment and one not. Suitable candidates for this trial have RDEB with a confirmed SCC case and are open to trying BVEC. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

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).

Is there any evidence suggesting that BVEC is likely to be safe for humans?

Research has shown that BVEC, the treatment under study, has been safe in previous studies. Long-term data suggest that BVEC is generally well-tolerated, with most people experiencing no problems. No serious side effects have been reported in connection with its use.

In earlier studies, wounds treated with BVEC were more likely to heal and remain healed compared to those treated with a placebo, which contains no active ingredients. This indicates promising safety and effectiveness. Although the current trial is in Phase 2, requiring further testing, the evidence so far supports BVEC's safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer recurrence?

Researchers are excited about BVEC because it represents a novel approach to preventing cancer recurrence through gene therapy. Unlike traditional treatments like chemotherapy and radiation, which target cancer cells directly, BVEC aims to modify the patient's genetic material to strengthen the body's natural defenses against cancer returning. This could mean a more personalized and potentially less toxic treatment option, providing hope for longer-lasting remission with fewer side effects.

What evidence suggests that BVEC might be an effective treatment for cancer recurrence?

Research has shown that BVEC, a type of gene therapy, may help treat Recessive Dystrophic Epidermolysis Bullosa (RDEB). In one study, wounds treated with BVEC healed better and stayed closed longer than untreated wounds. This finding is significant because it suggests BVEC might aid in proper skin healing after cancer surgery, possibly reducing the risk of cancer recurrence. Clinical data revealed that 67% of wounds healed within six months. In this trial, participants will either receive treatment with BVEC or no treatment with BVEC. These findings support the idea that BVEC could help prevent cancer from returning in RDEB patients. ^{1 5 6 7 8}

Who Is on the Research Team?

M. Peter Marinkovich, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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

Ability to understand and the willingness to provide written informed consent

Participant willingness to use an effective method of contraception

I have been diagnosed with RDEB due to COL7A1 mutations.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: No treatment with BVEC Active Control 1 Intervention

Group II: 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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06731933

Impact of COL7A1 Gene Therapy on SCC Recurrence in ... Recurrence rate of Squamous Cell Carcinoma, The outcome measure is recurrence rate of SCC following BVEC application at each SCC lesion, 2 years. Collaborators ...

2. withpower.com withpower.com/trial/gene-therapy-for-cancer-recurrence-e75fd

Gene Therapy 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11779647/

Efficacy and tolerability of neoadjuvant therapy with ... The 6-month relapse-free survival rate was 100%. With a median follow-up of 14 months (range 4.3–19.7 months) from the time point of the first T-VEC injection ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206663

Trial of Beremagene Geperpavec (B-VEC) for Dystrophic ... Over a period of 3 months, wounds that were exposed to B-VEC were more likely to have closure and remain healed than those exposed to placebo.

5. cgtlive.com cgtlive.com/view/dermatology-future-b-vec-impact-deb-6-months-post-approval

The Future of Dermatology? B-VEC's Impact in DEB 6 ... Clinical data from the GEM-3 study shows B-VEC's efficacy with a 67% wound healing rate at 6 months and reduced pain during dressing changes, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06731933?cond=(COMBINED%20OSTEOGENESIS%20IMPERFECTA%20EHLERS-DANLOS%20SYNDROME)%20OR%20(col7a1)&checkSpell=&rank=1

Study Details | Impact of COL7A1 Gene Therapy on SCC ... Recurrence rate of Squamous Cell Carcinoma, The outcome measure is recurrence rate of SCC following BVEC application at each SCC lesion, 2 years. Collaborators ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12227497/

Long-Term Safety and Tolerability of Beremagene ... The results of this open-label study build upon existing safety and tolerability data for beremagene geperpavec-svdt by demonstrating favorable ...

8. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/559555

Impact of COL7A1 Gene Therapy on SCC Recurrence in ... The study objective is to see if BVEC induced C7 expression in Recessive Dystrophic Epidermolysis Bullosa (RDEB) skin following Squamous ...