Chemoradiotherapy for Esophageal Cancer

Recruiting at 1 trial location

Overseen By Amy Abel

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: AHS Cancer Control Alberta

Disqualifiers: Other malignancy, Heart disease, Neurotoxicity, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 11

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating esophageal cancer by combining chemotherapy and radiation. Researchers aim to determine if a shorter, more intense treatment course, known as hypofractionated radiotherapy (a focused radiation treatment), is as effective as the usual longer one. Participants will receive specific drugs, carboplatin and paclitaxel, along with focused radiation treatment. Individuals with surgically removable esophageal adenocarcinoma and no signs of cancer spreading might be suitable for this study. As an unphased trial, this study allows participants to contribute to innovative research that could enhance future treatment options.

Will I have to stop taking my current medications?

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 hypofractionated neoadjuvant concurrent chemoradiotherapy is likely to be safe?

Research has shown that hypofractionated radiotherapy, a treatment under study for esophageal cancer, is generally well-tolerated. Studies indicate that this type of radiation therapy works effectively without increasing serious side effects compared to traditional methods. Specifically, patients receiving hypofractionated radiotherapy did not experience more negative effects. This suggests that the treatment is safe, with harmful side effects remaining at reasonable levels. Overall, the research supports the safety of hypofractionated radiotherapy for treating esophageal cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatment for esophageal cancer, which typically involves longer courses of chemoradiotherapy, hypofractionated radiotherapy offers a shorter, more intense approach. This method uses higher doses of radiation over fewer sessions, potentially reducing the overall treatment time. Researchers are excited about this treatment because it includes the combination of carboplatin and paclitaxel, which are well-known chemotherapy drugs, and aims to enhance the effectiveness of therapy while minimizing patient burden. This approach could lead to faster and potentially better outcomes for patients battling esophageal cancer.

What evidence suggests that hypofractionated radiotherapy might be an effective treatment for esophageal cancer?

In this trial, participants will receive hypofractionated radiotherapy combined with the drugs Carboplatin and Paclitaxel. Research has shown that this combination effectively treats esophageal cancer. Studies indicate that this method matches traditional treatments in extending patient survival and controlling cancer in the treated area. It does not increase side effects, making it manageable for patients. Additional research suggests it maintains stable patient outcomes without raising harmful effects. Overall, this treatment offers a promising alternative to standard therapies. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with biopsy-proven esophageal or gastroesophageal junction adenocarcinoma that's resectable and not spread beyond a certain stage. Participants must be in good enough health to start treatment within a month of consent, have adequate blood counts and organ function, and use effective contraception if capable of childbearing.

Inclusion Criteria

Maximum length of the tumor not exceeding 8 cm and width not exceeding 5 cm as seen on CT

Written and informed consent of patient

Patients capable of childbearing are using adequate contraception

Exclusion Criteria

Esophageal stent

Pregnant or lactating patients

Unable to complete surveys in English without aid of interpreter

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive carboplatin and paclitaxel intravenously weekly for 5 weeks

5 weeks

5 visits (in-person)

Radiation

Participants receive hypofractionated external beam radiotherapy in 5 fractions over 1 week

1 week

5 visits (in-person)

Surgery

Participants undergo esophagectomy 6-12 weeks after completion of chemoradiotherapy

6-12 weeks post-chemoradiotherapy

Follow-up

Participants are monitored for safety and effectiveness after surgery, including a final clinical follow-up with the radiation oncologist

60-90 days after surgery

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Hypofractionated radiotherapy

Trial Overview The study tests hypofractionated radiotherapy combined with chemotherapy before surgery in patients with esophageal cancer. It aims to determine if this less frequent radiation dosing schedule is as effective as the standard approach.

How Is the Trial Designed?

Group I: Hypofractionated neoadjuvant concurrent chemoradiotherapy Experimental Treatment 1 Intervention

Drug: Carboplatin and Taxol (paclitaxel) Patients will receive carboplatin (AUC 2) and paclitaxel (50 mg/m2) intravenously for 5 weeks on Days 1,8,15,22 and 29. Radiation: Hypofractionated radiation

Hypofractionated radiotherapy is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Hypofractionated radiotherapy for:

• Esophageal adenocarcinoma
• Gastroesophageal junction adenocarcinoma

Approved in United States as Hypofractionated radiotherapy for:

• Esophageal adenocarcinoma
• Gastroesophageal junction adenocarcinoma

Approved in Japan as Hypofractionated radiotherapy for:

• Esophageal squamous cell carcinoma
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Published Research Related to This Trial

In a clinical trial involving 201 patients with prostate cancer, the use of a hyaluronic acid rectal spacer significantly improved rectal dosimetry, with 98.5% of patients achieving a 25% or greater reduction in rectal volume receiving radiation, far exceeding the 70% target.

The spacer also reduced the incidence of acute grade 2 or higher gastrointestinal toxic effects, with only 2.9% of patients in the spacer group experiencing these effects compared to 13.8% in the control group, indicating a safer treatment option for hypofractionated radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyaluronic Acid Spacer for Hypofractionated Prostate Radiation Therapy: A Randomized Clinical Trial. Mariados, NF., Orio, PF., Schiffman, Z., et al.[2023]

Hypofractionated radiotherapy using three-dimensional conformal techniques showed a treatment tolerance rate of 78.8% for doses between 3 to 5 Gy, indicating it is a feasible option for patients with locally advanced esophageal carcinoma.

The study reported local control rates of 62%, 49%, and 39% at 1, 2, and 3 years respectively, with overall survival rates of 34%, 21%, and 9%, suggesting that while hypofractionated radiotherapy can be effective, there are significant risks of acute and late complications, necessitating further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of hypofractioned radiation with three-dimensional conformal radiotherapy for clinical T3-4N0-1M0 stage esophageal carcinoma. Song, YP., Ma, JB., Hu, LK., et al.[2018]

Hypofractionated radiotherapy (HFRT) for esophageal cancer is as effective and safe as conventional fractionated radiotherapy (CFRT), showing similar rates of pathological complete response and overall survival among 110 patients studied.

HFRT significantly reduces treatment time and costs compared to CFRT, making it a more efficient option for neoadjuvant treatment without compromising efficacy or increasing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of efficacy, safety, and costs between neoadjuvant hypofractionated radiotherapy and conventionally fractionated radiotherapy for esophageal carcinoma. Lyu, J., Liu, T., Li, T., et al.[2021]

Moderately hypofractionated radiotherapy (MHR) significantly improved local control rates in patients with thoracic esophageal cancer compared to conventional fractionated radiation (CFR), with a local/regional failure rate of 27.0% in the MHR group versus 47.3% in the CFR group.

Despite the improved local control, the overall survival rates at 3 and 5 years were similar between the two treatment groups, indicating that while MHR may enhance local disease management, it does not significantly impact long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderately hypofractionated conformal radiation treatment of thoracic esophageal carcinoma. Ma, JB., Wei, L., Chen, EC., et al.[2019]

In a study of 61 patients with oesophageal cancer who were unfit for chemoradiotherapy (CRT), hypofractionated radiotherapy (HRT) showed promising survival outcomes, with a 3-year overall survival rate of 56.9% and a median survival of 29 months, comparable to the 55.5% and 26 months seen in a CRT group.

HRT was associated with lower rates of severe toxicity (16.4%) compared to CRT (40.2%), indicating that HRT is a safe and tolerable treatment option for patients unable to undergo CRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated Radiotherapy in Oesophageal Cancer for Patients Unfit for Systemic Therapy: A Retrospective Single-Centre Analysis. Jones, CM., Spencer, K., Hitchen, C., et al.[2020]

The 7-month chemoradiotherapy regimen combining standard-dose radiotherapy, cisplatin, and continuous infusion 5-fluorouracil resulted in a 65% local tumor resolution rate in patients with locoregional esophageal cancer, indicating its efficacy in achieving local control.

Despite the high rate of tumor resolution, the treatment was associated with significant toxicity, including severe esophagitis and blood cell count issues, leading to hospitalizations in several patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy of esophageal carcinoma. Poplin, EA., Khanuja, PS., Kraut, MJ., et al.[2022]

In a study of 70 thoracic esophageal cancer patients treated with high-dose radiation therapy alone, the 2-year overall survival rate was 52.1%, indicating that this treatment can be effective for patients who cannot undergo surgery or chemotherapy.

The treatment resulted in a low incidence of severe toxicities (9.9%), with only 2.8% experiencing grade 3 esophagitis and 7.1% developing serious trachea-esophageal fistulas, suggesting that high-dose radiation therapy is a relatively safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose radiation therapy alone by moderate hypofractionation for patients with thoracic esophageal squamous cell carcinoma. Oh, D., Noh, JM., Nam, H., et al.[2022]

In a study of 211 patients with limited-stage small cell lung cancer, both conventional and hypofractionated intensity-modulated radiation therapy (IMRT) showed similar rates of radiation-related toxicities, indicating that hypofractionated IMRT is well-tolerated.

Key risk factors for acute esophagitis in the hypofractionated group included a mean esophageal dose of 13 Gy or more and significant overlap between the planning target volume and the esophagus, while chronic obstructive pulmonary disease (COPD) and tumor location were linked to lung injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy]. Zhao, JJ., Bi, N., Zhang, T., et al.[2023]

Hypofractionated radiation therapy (RT) alone is a feasible treatment option for early-stage esophageal squamous cell carcinoma (ESCC), showing a 5-year local control rate of 81.1% among 60 patients treated from 2004 to 2018.

Patients with tumors less than 3 cm had significantly better local control rates (95.7%) and lower rates of severe esophagitis and strictures compared to those with larger tumors, suggesting that smaller tumor size is a favorable indicator for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes following hypofractionated radiation therapy alone for surgically unfit early esophageal squamous cell carcinoma patients; a retrospective single center analysis. Kim, K., Oh, D., Noh, JM., et al.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0936655524001158

Systematic Review of Hypofractionated Radiation Therapy ... Hypofractionated radiotherapy has promising efficacy in oesophageal cancer. Moderately hypofractionated regimens appear well tolerated with reasonable toxicity.

2. journals.lww.com journals.lww.com/md-journal/fulltext/2016/08160/high_dose_radiation_therapy_alone_by_moderate.43.aspx

High-dose radiation therapy alone by moderate... : Medicine The 2-year overall survival (OS), cancer-specific survival (CSS) and local control (LC) rates were 52.1%, 57.8%, and 68.2%, respectively. Among them, 25 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31119872/

Comparison of efficacy, safety, and costs between ... Conclusion: Preoperative HFRT is effective and safe for esophageal cancer. Moreover, it is similar to CFRT in terms of overall survival and toxicity and is cost ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6639169/

Comparison of efficacy, safety, and costs between ... We conclude that HFRT has comparable efficacy to CFRT without increasing adverse effect rates or decreasing the pCR, PFS or OS.

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1138304/full

Moderately hypo-fractionated radiotherapy combined with ... A trial conducted by Song demonstrated that moderately hypofractionated radiation could improve the local control rate with tolerable toxicities in inoperable ...

6. thegreenjournal.com thegreenjournal.com/article/S0167-8140(23)89876-0/abstract

Outcomes following hypofractionated radiation therapy ... The 5-year rates of local control (LC), progression-free survival, cancer-specific survival, and overall survival were 81.1 %, 44.2 %, 73.7 %, and 54.5 % ...

7. elischolar.library.yale.edu elischolar.library.yale.edu/cgi/viewcontent.cgi?article=4276&context=ymtdl

Outcomes Following Hypofractionated Radiotherapy For ... Our research examines whether HD-. HFRT enhances local control (LC) and overall survival (OS) rates while maintaining comparable rates of grade 3+ toxicity to ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04046575

Study Details | NCT04046575 | Radiation Dose ... Recent clinical trials for lung cancer have demonstrated that local tumor control can be improved safely with accelerated hypofractionated radiation therapy ...