Proton Therapy + Chemotherapy for Esophageal Cancer

Overseen By John Plastaras, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Abramson Cancer Center of the University of Pennsylvania

Must be taking: Carboplatin, Paclitaxel

Disqualifiers: Large tumors, Prior malignancies, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

30 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Proton Therapy + Chemotherapy for Esophageal Cancer?

Research shows that combining paclitaxel and carboplatin with radiation therapy is effective for treating esophageal cancer, with many patients experiencing significant tumor shrinkage. Additionally, a study found that this combination led to a high rate of complete response in patients with localized esophageal cancer. ^{1 2 3 4 5}

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

The combination of carboplatin and paclitaxel, often used with radiation, has been generally well-tolerated in patients with esophageal cancer, with common side effects including neutropenia (low white blood cell count) and esophagitis (inflammation of the esophagus). These side effects were manageable, and the treatment was considered to have acceptable safety in clinical trials. ^{1 3 4 6 7}

What makes the Proton Therapy + Chemotherapy treatment for esophageal cancer unique?

This treatment is unique because it combines proton beam therapy, which precisely targets tumors while sparing healthy tissue, with chemotherapy, potentially reducing side effects compared to traditional radiation therapies. Proton therapy's ability to limit radiation exposure to critical organs like the heart and lungs may lead to fewer complications and better outcomes for patients with esophageal cancer. ^{1 8 9 10 11}

What is the purpose of this trial?

Patients with esophageal cancer to be treated with concurrent preoperative proton therapy along with carboplatin and paclitaxel.

Research Team

John Plastaras, MD

Principal Investigator

Abramson Cancer Center at Penn Medicine

Eligibility Criteria

This trial is for adults over 18 with locally advanced esophageal cancer, specifically adenocarcinoma located below the carina. They must be fit for surgery and have good organ function, not be pregnant or nursing, and agree to use birth control if of childbearing potential. Tumors must not exceed certain sizes.

Inclusion Criteria

I am older than 18 years.

I can carry out all my usual activities without help.

Patients must be able to provide informed consent

Exclusion Criteria

My primary tumor is larger than 8 cm long or 5 cm wide.

My primary tumor is located in the upper part of my lungs.

I have not had any cancer other than skin or thyroid cancer in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dose-escalated proton radiotherapy with concurrent chemotherapy (carboplatin and paclitaxel) in the preoperative setting

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of pathologic response rates by esophagectomy surgical specimens

4 weeks

Treatment Details

Interventions

• Carboplatin
• Paclitaxel
• Proton Beam Radiotherapy

Trial Overview The study tests increasing doses of preoperative proton beam radiotherapy combined with chemotherapy drugs Carboplatin and Paclitaxel in patients with esophageal cancer to see how well they tolerate it before surgery.

Participant Groups

Group I: Dose Escalation of Neoadjuvant Proton Radiotherapy in Esophageal Cancer Experimental Treatment 3 Interventions

Patients with esophageal cancer to be treated with concurrent preoperative chemoradiation with carboplatin and paclitaxel.

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?

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Findings from Research

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]

This randomized phase II trial is comparing the efficacy and toxicity of two chemoradiation regimens, OXCAP-RT and CarPac-RT, in patients with resectable oesophageal adenocarcinoma, with a primary focus on achieving a pathological complete response rate (pCR) after treatment.

The study involves 76 patients and aims to determine which regimen is more effective and safer, potentially leading to a future phase III trial against the current standard neo-adjuvant chemotherapy in the UK.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NEOSCOPE: a randomised Phase II study of induction chemotherapy followed by either oxaliplatin/capecitabine or paclitaxel/carboplatin based chemoradiation as pre-operative regimen for resectable oesophageal adenocarcinoma. Mukherjee, S., Hurt, CN., Gwynne, S., et al.[2023]

In a phase II study involving 17 patients with advanced esophageal or gastric cancer, carboplatin and paclitaxel demonstrated promising efficacy, with partial responses observed in 3 out of 5 patients with esophageal cancer and 3 patients with gastric cancer.

The treatment regimen was well tolerated, with no cases of neutropenic fever reported, suggesting that outpatient administration of carboplatin and paclitaxel is a safe option for patients with advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of carboplatin and paclitaxel in the treatment of patients with advanced esophageal and gastric cancer. Philip, PA., Zalupski, MM., Gadgeel, S., et al.[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 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]

In a study of 41 patients with esophageal cancer, the combination of paclitaxel, cisplatin, and concurrent radiation resulted in a 29% complete response rate, indicating its efficacy in treating this type of cancer.

The treatment was associated with manageable toxicity, with only 24% of patients experiencing severe neutropenia and 5% suffering from severe esophagitis, suggesting that the regimen is relatively safe and does not require additional feeding support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, cisplatin, and concurrent radiation for esophageal cancer. Safran, H., Gaissert, H., Akerman, P., et al.[2019]

In a phase II study involving 23 previously untreated patients with stages IIIA or IIIB non-small cell lung cancer, the combination of paclitaxel, carboplatin, and concurrent radiation achieved a high overall response rate of 82%.

The treatment was associated with manageable toxicity, primarily esophagitis, affecting 45% of patients, but most recovered quickly, indicating that this regimen is a promising option for locally advanced lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin and concurrent radiation therapy for patients with locally advanced non-small cell lung cancer. Choy, H., Akerley, W., Safran, H., et al.[2015]

Proton beam radiation therapy (PT) offers significant advantages over traditional photon radiation therapy for esophageal cancer, including reduced toxicity to healthy tissues and improved safety for tumors located near critical organs, as supported by recent multicenter studies.

A randomized phase II study confirmed that PT resulted in significantly lower toxicities compared to IMRT, and ongoing phase III trials are investigating whether PT could become the standard treatment for locally advanced and resectable esophageal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The role of proton therapy in esophageal cancer]. Créhange, G., Goudjil, F., Krhili, SL., et al.[2022]

In a study of 44 patients with clinical T1 esophageal squamous cell carcinoma (ESCC) treated with concurrent chemo-proton therapy (CCPT), 98% achieved a complete response, indicating high efficacy of this treatment approach.

The 3-year overall survival rate was 95.2%, and even among the 11% who experienced local recurrence, all were successfully treated and remained recurrence-free after a median follow-up of 23 months, highlighting the safety and effectiveness of salvage endoscopic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic results of proton beam therapy with concurrent chemotherapy for cT1 esophageal cancer and salvage endoscopic therapy for local recurrence. Sato, D., Motegi, A., Kadota, T., et al.[2021]

References

1. 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]

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

NEOSCOPE: a randomised Phase II study of induction chemotherapy followed by either oxaliplatin/capecitabine or paclitaxel/carboplatin based chemoradiation as pre-operative regimen for resectable oesophageal adenocarcinoma. [2023]

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

A phase II study of carboplatin and paclitaxel in the treatment of patients with advanced esophageal and gastric cancer. [2015]

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

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

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. England pubmed.ncbi.nlm.nih.gov

Paclitaxel, cisplatin, and concurrent radiation for esophageal cancer. [2019]

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

Paclitaxel plus carboplatin and concurrent radiation therapy for patients with locally advanced non-small cell lung cancer. [2015]

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

Proton Therapy With Concurrent Chemotherapy for Thoracic Esophageal Cancer: Toxicity, Disease Control, and Survival Outcomes. [2023]

9. France pubmed.ncbi.nlm.nih.gov

[The role of proton therapy in esophageal cancer]. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

Therapeutic results of proton beam therapy with concurrent chemotherapy for cT1 esophageal cancer and salvage endoscopic therapy for local recurrence. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Dosimetric rationale and preliminary experience in proton plus carbon-ion radiotherapy for esophageal carcinoma: a retrospective analysis. [2023]