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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effects of a new treatment combination for esophageal or gastroesophageal cancer that has spread to nearby areas. The treatment combines a virus called OBP-301 (Telomelysin™), which targets and destroys cancer cells, with chemotherapy drugs carboplatin and paclitaxel, and radiation therapy. Researchers aim to determine if this combination is more effective than standard treatments. Suitable participants have esophageal or gastroesophageal cancer confirmed by a doctor, affecting nearby structures but not distant organs. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining OBP-301, also known as Telomelysin, with other treatments is generally well-tolerated. Studies found OBP-301 to be safe when used with radiation therapy in patients with esophageal cancer. Patients did not report major safety concerns, indicating it is a manageable option.

Carboplatin and paclitaxel, two chemotherapy drugs included in the trial, are also considered relatively safe. These drugs are often used together and rarely cause severe side effects. Common side effects like diarrhea and vomiting are usually manageable.

Radiation therapy is another part of the treatment. While it can cause side effects, such as discomfort in the esophagus, it is generally safe when carefully monitored.

Overall, the treatments used in this trial have been studied before and are considered well-tolerated. However, since this is an early-phase trial, the main focus is on further assessing safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about this treatment for esophageal cancer because it combines a novel anti-cancer viral therapy, Telomelysin™, with traditional chemoradiation. Unlike standard treatments that primarily involve chemotherapy and radiation, this approach uses Telomelysin™, an oncolytic virus, to specifically target and destroy cancer cells by replicating within them, causing the cells to burst. This method not only aims to enhance the effectiveness of chemotherapy drugs like carboplatin and paclitaxel but also potentially boosts the overall response to radiation therapy. By introducing this new mechanism of action, there's hope for improved outcomes and fewer side effects for patients.

What evidence suggests that this trial's treatments could be effective for esophageal cancer?

In this trial, participants will receive a combination of OBP-301 (Telomelysin), carboplatin, paclitaxel, and radiation therapy. Research has shown that OBP-301 targets cancer cells without harming normal cells and shows promise when combined with radiation, potentially benefiting patients with esophageal cancer. Studies have found that adding OBP-301 to treatments can enhance radiation's effectiveness by disrupting cancer cells' DNA repair.

Carboplatin and paclitaxel, two chemotherapy drugs included in this trial, have successfully treated esophageal cancer by killing cancer cells or stopping their growth. Research has shown that combining these drugs with radiation led to a complete response rate of 80% in some cases, meaning no detectable cancer after treatment.

Radiation therapy, often used with these chemotherapy drugs, is a proven method to kill cancer cells and shrink tumors. Together, these treatments in this trial could provide a more thorough attack on the cancer, potentially improving patient outcomes. ^{1 2 6 7 8}

Who Is on the Research Team?

Geoffrey Y Ku

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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 and on days 1, 8, 15, 22, and 29, and undergo radiation therapy (1.8 Gy/faction) 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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6627268/

Efficacy and Toxicity of Weekly Carboplatin and Paclitaxel as ... This weekly regimen appeared to be very tolerable and effective with an overall response rate of 54%. Therefore, this regimen was utilized for ...

2. journals.lww.com journals.lww.com/crst/fulltext/2022/05020/efficacy_and_safety_of_induction_weekly_paclitaxel.10.aspx

Efficacy and safety of induction weekly paclitaxel and... [11] Concurrent paclitaxel and carboplatin administered once-in-3-weeks is an effective treatment in patients with non-metastatic esophageal cancer with an ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8687861/

Chemoradiation with Weekly Paclitaxel and Carboplatin in ... Overall CR rate was 80%. The median overall survival was 14 months, and 1-year survival was 57%. Conclusion Definitive CRT in esophageal SCC using weekly ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)61852-1/fulltext

A phase II study of carboplatin and paclitaxel in ... The median survival time was 9 months (90%CI 7–13.8) and the 1-year survival rate was 43% (90% CI 0.29–0.57). The major grade 3–4 toxicity observed was ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.e16526

Study of efficacy and tolerability of paclitaxel ... Results: 23 out 64 patients underwent surgery while others were either lost to follow up or they refused for surgery. Of these 23, 87.5% could ...

6. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-022-02190-4

Safety and efficacy of paclitaxel plus carboplatin versus ... We evaluated and compared the efficacy and safety of chemotherapy with paclitaxel plus cisplatin (TP) or carboplatin (TC) in patients with ...

7. wcrj.net wcrj.net/article/2399

Comparison of survival and adverse effect profile in ... The major side-effect seen in patients treated with the combination of Carboplatin and Paclitaxel was diarrhoea/vomiting (4.52%), followed by mucositis (3.39%) ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.370

Trimodality therapy with carboplatin/paclitaxel (CP) or ... Main secondary endpoints were nCRT and postoperative safety (NCI CTCAE v.4), DFS and OS. Results: 41/50 (82%) and 39/50 (78 %) pts received the ...