Intense Radiation + Chemotherapy for Esophageal Cancer

Not currently recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treat advanced esophageal cancer that cannot be surgically removed. It combines intense radiation with chemotherapy drugs, carboplatin (also known as Paraplatin or Carboplatinum) and paclitaxel (also known as Taxol, Onxol, or Abraxane), to determine if this combination can better control the cancer locally. The trial targets individuals with esophageal cancer for whom surgery is not an option. Participants must have a confirmed diagnosis and be eligible for this combined treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new therapy.

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.

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

Research has shown that using carboplatin, paclitaxel, and intensity-modulated radiation therapy (IMRT) together has been studied for safety. Other studies have found that carboplatin and paclitaxel are generally safe, with manageable side effects. One study suggested that this drug pair is safer than others, making it a good choice for outpatient treatment.

IMRT, even at higher doses, has not been linked to more harmful side effects. However, debate remains about its overall safety for treating esophageal cancer, indicating a need for further research.

These treatments are often used together and are generally well-tolerated, though individual reactions can vary. Like any treatment, side effects might occur, but past research considers this combination relatively safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for esophageal cancer because it combines Intensity Modulated Radiation Therapy (IMRT) with simultaneous integrated boost, and the chemotherapy drugs carboplatin and paclitaxel. Unlike traditional treatments, which often involve longer radiation schedules, this approach uses a more intense, hypofractionated radiation over just three weeks. This could potentially lead to faster and more effective tumor reduction. Additionally, the combination of carboplatin and paclitaxel enhances the cancer-killing effects of the radiation, possibly offering improved outcomes compared to standard treatments like surgery and conventional chemoradiation.

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

In this trial, participants will receive a combination of intensity-modulated radiation therapy (IMRT) with the drugs carboplatin and paclitaxel. Research has shown that IMRT with these drugs can yield positive results in treating chest cancers. Studies have found that high doses of IMRT might extend patient survival without increasing side effects. Additionally, the combination of paclitaxel and carboplatin has proven effective and safe for individuals with advanced cancers. These treatments aim to target the cancer more precisely and aggressively, potentially improving disease control. Overall, this combination has shown promise in enhancing outcomes for patients with difficult-to-treat cancers. ^{1 2 4 6 7}

Who Is on the Research Team?

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

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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

Severe active comorbidity as defined below:

I do not have brain metastases.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4088233/

Intensity-modulated radiation therapy with concurrent ... In conclusion, concurrent IMRT and chemotherapy resulted in an encouraging tumor response in patients with locally advanced cervical and upper thoracic ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0360301622035209

High-Dose Versus Standard-Dose Intensity-Modulated ... We investigated whether a high dose of 59.4 Gy using intensity-modulated radiation therapy (IMRT) would improve survival without increasing toxicities.

3. 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04046575

Study Details | NCT04046575 | Radiation Dose ... This clinical trial aims to adapt those techniques and assess the safety of such a regimen for the treatment of inoperable thoracic esophageal cancers. Official ...

5. redjournal.org redjournal.org/article/S0360-3016(22)03520-9/pdf

Modulated Radiotherapy With Concurrent Paclitaxel Plus ... Although retrospective studies have reported SIB as a safe and effective therapy option19,20 with similar survival and toxicity profiles to the sequential boost ...

6. redjournal.org redjournal.org/article/S0360-3016(16)31328-1/fulltext

Outcomes and Toxicity in Patients Treated With Intensity ... There is not yet a consensus on the efficacy and safety of IMRT for the treatment of patients with esophageal carcinomas.

7. tandfonline.com tandfonline.com/doi/full/10.1080/0284186X.2020.1753889

A national study to assess outcomes of definitive ... Based on the superior safety profile, in addition to a more feasible outpatient implementation, we suggest a CRT regimen with carboplatin and paclitaxel in the ...