Intense Radiation + Chemotherapy for Esophageal Cancer

Overseen By Gregory Vlacich, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Investigational agents

Disqualifiers: Brain metastases, Active malignancy, others

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

Compensation: Varies

Number of Visits: 1

Duration: 3 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Rates of local disease control in patients with locally advanced esophageal cancer who are not candidates for surgical resection are suboptimal. Despite treatment with chemotherapy and radiation therapy approximately half of patients will develop recurrence of their cancer at the site of the original primary cancer. Salvage therapy options are largely ineffective and nearly all patients who develop local disease recurrence will succumb to their cancer. Recent clinical trials for lung cancer have demonstrated that local tumor control can be improved safely with accelerated hypofractionated radiation therapy regimens in order to achieve radiation dose intensification. This clinical trial aims to adapt those techniques and assess the safety of such a regimen for the treatment of inoperable thoracic esophageal cancers.

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

The trial information does not specify if you need to stop taking your current medications. However, if you are on investigational agents or planning to undergo induction chemotherapy, you cannot participate. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment involving intense radiation and chemotherapy for esophageal cancer?

Research shows that a combination of paclitaxel and carboplatin with radiation therapy is highly active in treating esophageal cancer, with a high rate of complete response in patients who underwent surgery after treatment. This suggests that the treatment can be effective in managing esophageal cancer. ^{1 2 3 4 5}

Is the combination of intense radiation and chemotherapy safe for treating esophageal cancer?

The combination of paclitaxel and carboplatin with radiation therapy for esophageal cancer has been studied and found to be relatively well tolerated, with manageable side effects like neutropenia (low white blood cell count) and esophagitis (inflammation of the esophagus). Safety data from other studies also confirm the safety of similar regimens, although some patients may experience significant side effects. ^{3 6 7 8 9}

How is the treatment of intense radiation and chemotherapy with carboplatin and paclitaxel unique for esophageal cancer?

This treatment combines intense radiation with chemotherapy using carboplatin and paclitaxel, which is unique because it uses Intensity Modulated Radiation Therapy (IMRT) to precisely target the cancer, potentially reducing damage to surrounding healthy tissue. The combination of these specific drugs with IMRT is not yet well-established, making it a novel approach compared to other regimens that may use different drug combinations or radiation techniques. ^{1 2 3 4 10}

Research Team

Gregory Vlacich, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with inoperable esophageal cancer who can't have surgery. They should be able to handle chemoradiation, have a performance status showing they're relatively active (ECOG 0-2), and their blood counts and organ functions need to meet specific criteria. Pregnant or breastfeeding women can't join, nor can those with certain other health issues or recent major surgeries.

Inclusion Criteria

My cancer is in the esophagus or where the stomach meets the esophagus.

I am scheduled for IMRT photon beam therapy, not 3D CRT or proton therapy.

My kidney function, based on creatinine clearance, is within the required range.

Exclusion Criteria

I do not have brain metastases.

Severe active comorbidity as defined below:

I have had no major surgery complications in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Concurrent chemoradiation with hypofractionated intensity modulated radiation therapy (IMRT) and simultaneous integrated boost (SIB) for 3 weeks with carboplatin and paclitaxel for 3 cycles every 7 days

3 weeks

Weekly visits for chemotherapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including endoscopy and optional PET/CT within 6-8 weeks post-completion of chemoradiation

6-8 weeks

1-2 visits (in-person)

Long-term follow-up

Participants are monitored for local relapse-free survival and other patient-reported outcomes

24 months

Treatment Details

Interventions

• Carboplatin
• Intensity Modulated Radiation Therapy
• Paclitaxel

Trial Overview The study tests if intensifying radiation therapy using an accelerated hypofractionated method along with chemotherapy drugs Carboplatin and Paclitaxel improves outcomes in patients with advanced esophageal cancer. It also includes various assessments like symptom inventories, quality of life questionnaires, social support measures, and optional blood tests for tumor DNA.

Participant Groups

Group I: IMRT + Carboplatin + Paclitaxel Experimental Treatment 10 Interventions

Concurrent chemoradiation will consist of hypofractionated intensity modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) for 3 weeks with carboplatin and paclitaxel for 3 cycles every 7 days. Endoscopy and (optional) PET/CT within 6-8 weeks post-completion of chemoradiation.

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?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Findings from Research

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 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]

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 study of 15 patients with locally advanced esophageal squamous cell carcinoma (SCC), the neoadjuvant chemoradiation regimen using weekly paclitaxel and carboplatin resulted in a clinical complete response rate of 66% and an overall complete response rate of 80%.

The treatment was generally well tolerated, with manageable toxicities, and led to a median overall survival of 14 months, suggesting it could be a new standard of care for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiation with Weekly Paclitaxel and Carboplatin in Esophageal Squamous Cell Carcinoma: A Prospective Study. Joseph, DM., Malik, MI., Jonnadula, J., et al.[2021]

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]

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 safety analysis of 6 patients with locally advanced esophageal cancer, the combination of pemetrexed, carboplatin, and radiation followed by surgery showed a favorable safety profile, with only one patient experiencing a severe adverse event (grade 4 neutropenia).

The treatment resulted in promising outcomes, with one patient achieving a complete pathologic response and three showing partial responses, indicating potential efficacy that warrants further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed, Carboplatin, and Concomitant Radiation followed by Surgery for Locally Advanced Esophageal Cancer: Results of a Planned Interim Toxicity Analysis of North Central Cancer Treatment Group Study N044E. Katipamula, R., Jatoi, A., Foster, NR., et al.[2021]

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]

References

1. 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]

2. 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]

3. 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]

4. 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]

5. 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]

6. India pubmed.ncbi.nlm.nih.gov

Chemoradiation with Weekly Paclitaxel and Carboplatin in Esophageal Squamous Cell Carcinoma: A Prospective Study. [2021]

7. England pubmed.ncbi.nlm.nih.gov

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

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

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

9. New Zealand pubmed.ncbi.nlm.nih.gov

Pemetrexed, Carboplatin, and Concomitant Radiation followed by Surgery for Locally Advanced Esophageal Cancer: Results of a Planned Interim Toxicity Analysis of North Central Cancer Treatment Group Study N044E. [2021]

10. 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]