Anti-Cancer Viral Therapy + Chemoradiation for Esophageal Cancer

Recruiting at 16 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: NRG Oncology

Must not be taking: Immunosuppressants, Steroids, TNF-alpha blockers

Disqualifiers: Metastatic disease, Cardiac disease, Diabetes, others

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

Compensation: Varies

Number of Visits: 1

Duration: 5.5 weeks

16 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of a special virus, two chemotherapy drugs, and radiation therapy in patients with advanced esophageal or gastroesophageal cancer. The virus aims to kill cancer cells directly, while the chemotherapy and radiation help stop the cancer from growing and spreading.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive medications or require chronic steroid therapy, you may need to stop them at least 7 days before joining the study.

What data supports the effectiveness of the treatment Anti-Cancer Viral Therapy + Chemoradiation for Esophageal Cancer?

Research shows that combining paclitaxel and carboplatin with radiation therapy has been effective in treating esophageal cancer, with high response rates and manageable side effects. In one study, 69% of patients with localized esophageal cancer had a complete response after treatment with these drugs and radiation. ^{1 2 3 4 5}

Is the combination of paclitaxel, carboplatin, and radiation therapy safe for treating esophageal cancer?

Studies have shown that combining paclitaxel, carboplatin, and radiation therapy is generally safe for treating esophageal cancer, although it can cause some side effects. These treatments are often used together because they can work well against cancer, but they may also lead to side effects like esophageal irritation and other toxicities. ^{2 3 4 6 7}

What makes the Anti-Cancer Viral Therapy + Chemoradiation treatment for esophageal cancer unique?

This treatment is unique because it combines traditional chemoradiation with Telomelysin™, a viral therapy that targets cancer cells, potentially enhancing the effectiveness of the treatment by directly attacking the cancer cells while also using chemotherapy and radiation to shrink the tumor. ^{2 3 4 8 9}

Research Team

Geoffrey Y Ku

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for adults with advanced esophageal or gastroesophageal cancer who can't have surgery. They must be in good physical condition, not pregnant, and willing to use contraception. People with other cancers that won't affect this study can join too. But those with certain infections, previous treatments for their cancer, or serious health issues like uncontrolled diabetes cannot participate.

Inclusion Criteria

I have another cancer that does not affect this treatment's safety or effectiveness.

I am not pregnant and agree to use birth control.

I have completed all required tests for my lung cancer diagnosis.

Exclusion Criteria

I do not have uncontrolled diabetes or an active infection needing IV antibiotics.

I have a history of heart disease.

My cancer has spread to nearby structures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive OBP-301 by intratumoral injection, carboplatin, paclitaxel, and radiation therapy

5.5 weeks

Multiple visits for injections and radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Follow-up at 1 and 6-8 weeks, then every 3 months

Treatment Details

Interventions

• Carboplatin
• Paclitaxel
• Radiation Therapy
• Telomelysin™

Trial Overview The trial tests Telomelysin™ (OBP-301), a virus targeting cancer cells, combined with chemotherapy drugs carboplatin and paclitaxel plus radiation therapy. The goal is to see if this mix works better than the usual chemo and radiation for these types of cancer.

Participant Groups

Group I: Treatment (OBP-301, carboplatin, paclitaxel, radiation) Experimental Treatment 4 Interventions

Patients receive OBP-301(1×10\^12 vp/mL) by intra-tumoral injection via endoscopy on days -3, 12, and 26. Patients also receive paclitaxel IV (50 mg/m\^2) over 60 minutes followed by carboplatin IV (AUC 2) over 30 minutes on days 1, 8, 15, 22, and 29, and undergo radiation therapy on Monday through Friday beginning day 1 for 28 fractions (50.4 Gy total) over 5.5 weeks. All treatment continues in the absence of disease progression or unacceptable toxicity.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 201 patients with locally advanced esophageal squamous cell carcinoma, the chemotherapy regimen of carboplatin plus paclitaxel (TP) resulted in significantly higher rates of severe adverse events compared to carboplatin plus cisplatin (TC), particularly with a higher incidence of grade 3 or higher febrile neutropenia.

Despite the differences in safety, both TP and TC regimens showed comparable overall survival and progression-free survival rates, suggesting that TC is the preferred option due to its better safety profile without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of paclitaxel plus carboplatin versus paclitaxel plus cisplatin in neoadjuvant chemoradiotherapy for patients with locally advanced esophageal carcinoma: a retrospective study. Jiang, L., Zhu, J., Chen, X., et al.[2023]

In a Phase I study involving 12 patients with advanced esophageal cancer, the combination of UFT/leucovorin, carboplatin, and paclitaxel with radiation therapy showed preliminary efficacy, with 2 out of 3 patients achieving a pathologic complete response after treatment at the higher dose level.

The study identified maximum tolerated doses for the regimen, but also noted significant toxicity, including febrile neutropenia in multiple patients, indicating that while the treatment may be effective, it carries a risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of UFT/leucovorin, carboplatin, and paclitaxel in combination with external beam radiation therapy for advanced esophageal carcinoma. Czito, BG., Cohen, DP., Kelsey, CR., et al.[2015]

Combined treatment of radiotherapy with cisplatin and etoposide has shown significant improvements in local control and survival rates for patients with locally advanced non-small cell lung cancer (NSCLC), with median survival rates reported between 15-18 months and 2-year survival rates around 35-40%.

Recent advancements in radiation technology and the use of third-generation chemotherapy drugs have led to promising results, including median survival exceeding 20 months, although careful management of treatment to minimize toxicity, particularly esophageal toxicity, remains crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy and chemotherapy in locally advanced non-small cell lung cancer: preclinical and early clinical data. Reboul, FL.[2019]

In a randomized clinical trial involving 321 patients with esophageal squamous cell carcinoma (ESCC), the overall survival rates after 3 years were similar across three treatment regimens: paclitaxel with fluorouracil (57.2%), cisplatin (60.1%), and carboplatin (56.5%), indicating no significant superiority of one regimen over the others.

The cisplatin regimen was associated with significantly higher rates of severe side effects, including neutropenia (60.8%), thrombocytopenia (13.1%), and gastrointestinal issues, compared to the fluorouracil and carboplatin groups, suggesting that while all regimens are effective, cisplatin may pose greater risks for adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of 3 Paclitaxel-Based Chemoradiotherapy Regimens for Patients With Locally Advanced Esophageal Squamous Cell Cancer: A Randomized Clinical Trial. Ai, D., Ye, J., Wei, S., et al.[2022]

In a study of 38 patients with upper aerodigestive tract cancers, a novel chemotherapy regimen combining paclitaxel, carboplatin, and continuous infusion 5-fluorouracil showed a high overall response rate, with 25 out of 29 evaluable patients achieving major responses.

The regimen was particularly effective for localized esophageal cancer, with 69% of patients undergoing resection achieving a pathologic complete response, indicating strong efficacy when used alongside radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, carboplatin, and long-term continuous 5-fluorouracil infusion in the treatment of upper aerodigestive malignancies: preliminary results of phase II trial. Hainsworth, JD., Meluch, AA., Greco, FA.[2015]

A phase II clinical trial involving 50 patients with esophageal cancer showed that a treatment regimen of paclitaxel, carboplatin, and radiation, with or without surgery, is well tolerated and has promising efficacy, with 26% of patients achieving a complete response.

The median survival rates were encouraging, with 12 months for metastatic disease and over 44 months for localized disease treated with either surgery or definitive chemoradiotherapy, indicating that this alternative treatment may be effective for various stages of esophageal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of paclitaxel, carboplatin, and radiation with or without surgery for esophageal cancer. Wang, H., Ryu, J., Gandara, D., et al.[2015]

In a study of 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

In a phase I study involving 13 patients with esophageal cancer, the combination of capecitabine, carboplatin, and paclitaxel with radiation therapy showed promising activity, with 2 out of 6 patients achieving a pathologic complete response after surgery.

The recommended doses for further studies were determined to be capecitabine 600 mg/m² twice daily, carboplatin AUC 1.5, and paclitaxel 45 mg/m² weekly, but the treatment was associated with significant toxicities, particularly Grade 4 esophagitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma. Czito, BG., Kelsey, CR., Hurwitz, HI., et al.[2015]

Preoperative chemoradiation therapy can improve survival rates in patients with adenocarcinoma of the esophagus, while it does not show the same benefit for those with squamous cell carcinoma, highlighting the importance of histology in treatment effectiveness.

Paclitaxel has demonstrated a 32% overall response rate and a median survival of 13.2 months in patients with advanced esophageal cancer, and its use in combination with radiation therapy and other drugs shows promise for enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent paclitaxel and thoracic irradiation for locally advanced esophageal cancer. Blanke, CD., Choy, H., Teng, M., et al.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of paclitaxel plus carboplatin versus paclitaxel plus cisplatin in neoadjuvant chemoradiotherapy for patients with locally advanced esophageal carcinoma: a retrospective study. [2023]

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

A phase I study of UFT/leucovorin, carboplatin, and paclitaxel in combination with external beam radiation therapy for advanced esophageal carcinoma. [2015]

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

Radiotherapy and chemotherapy in locally advanced non-small cell lung cancer: preclinical and early clinical data. [2019]

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

Comparison of 3 Paclitaxel-Based Chemoradiotherapy Regimens for Patients With Locally Advanced Esophageal Squamous Cell Cancer: A Randomized Clinical Trial. [2022]

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

Paclitaxel, carboplatin, and long-term continuous 5-fluorouracil infusion in the treatment of upper aerodigestive malignancies: preliminary results of phase II trial. [2015]

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

A phase II study of paclitaxel, carboplatin, and radiation with or without surgery for esophageal cancer. [2015]

7. China pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. [2010]

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

A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma. [2015]

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

Concurrent paclitaxel and thoracic irradiation for locally advanced esophageal cancer. [2015]