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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for esophageal cancer, which affects the tube connecting the throat to the stomach. Researchers aim to determine if combining proton beam therapy (a precise type of radiation) with two chemotherapy drugs, carboplatin (Paraplatin) and paclitaxel (Taxol), is effective when administered before surgery. The goal is to identify the safest dose of proton therapy to use with these drugs. Suitable participants have esophageal cancer diagnosed as adenocarcinoma and plan to undergo surgery. 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 innovative approach.

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.

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

Research shows that proton therapy is a safe and effective treatment for esophageal cancer. Studies suggest it may cause fewer heart and lung side effects compared to traditional radiation.

The chemotherapy drugs carboplatin and paclitaxel have been used safely in cancer treatments. Reports indicate that side effects like diarrhea and vomiting occur in less than 5% of patients. Overall, these drugs are effective with manageable side effects.

This trial is in an early stage and primarily focuses on safety, so there is limited information on treatment tolerance. However, existing evidence from other studies suggests that these treatments are generally safe for patients with esophageal cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of proton therapy and chemotherapy for esophageal cancer because it offers a unique approach compared to current treatment options. Unlike traditional radiation therapy, proton beam radiotherapy precisely targets the tumor, potentially reducing damage to surrounding healthy tissues and minimizing side effects. Additionally, the use of carboplatin and paclitaxel in conjunction with proton therapy may enhance the effectiveness of the treatment, increasing the chances of shrinking the tumor before surgery. This combination aims to improve outcomes for patients with esophageal cancer by offering a more targeted and potentially less toxic treatment option.

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

Research has shown that proton beam radiotherapy (PBT) holds promise for treating esophageal cancer. It reduces harmful side effects and improves survival rates compared to traditional photon therapy. Studies indicate that PBT results in a 2.3 times lower total toxicity burden. In this trial, participants will receive PBT combined with the chemotherapy drugs carboplatin and paclitaxel. When used together, carboplatin and paclitaxel have proven effective in treating esophageal cancer; one study found an 80% complete response rate with this combination. These drugs are also well-tolerated, causing fewer severe side effects and helping improve survival rates for patients. ^{2 6 7 8 9}

Who Is on the Research Team?

John Plastaras, MD

Principal Investigator

Abramson Cancer Center at Penn Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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 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]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9801619/

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 locally advanced ...

7. 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 ...

8. 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%) ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT01249443

Paclitaxel and Carboplatin in Treating Patients With ... The primary objective going forward will determine the safety and tolerability of the paclitaxel and carboplatin combination in this patient population.