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

Trial Summary

What is the purpose of this trial?

An open-label, single-centre, non-randomized, Phase II trial in patients with esophageal adenocarcinoma. This study aims to show that delivering hypofractionated neoadjuvant concurrent chemoradiotherapy is is equally effective as conventionally fractionated neoadjuvant concurrent chemoradiotherapy.

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.

What data supports the effectiveness of the treatment Hypofractionated radiotherapy for esophageal cancer?

Research shows that hypofractionated radiotherapy can be effective for esophageal cancer, with studies reporting survival rates and local control of the disease. For example, one study found that patients with early-stage esophageal cancer had a 2-year overall survival rate of 80% when treated with this method. ^{1 2 3 4 5}

Is hypofractionated radiotherapy safe for esophageal cancer?

Hypofractionated radiotherapy for esophageal cancer has been studied, and while it can cause some side effects like esophageal complications, it is generally considered manageable and tolerated by patients. However, higher doses may lead to more severe side effects, so careful dosing is important. ^{1 3 5 6 7}

How is hypofractionated radiotherapy different from other treatments for esophageal cancer?

Hypofractionated radiotherapy for esophageal cancer involves delivering higher doses of radiation in fewer sessions compared to conventional radiotherapy, which can be beneficial for patients who are not fit for surgery or standard chemoradiotherapy. This approach aims to achieve effective tumor control with a shorter treatment duration, although it may come with a higher risk of certain side effects. ^{1 4 5 8 9}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

References

1. Ireland 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. [2023]

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

Comparison of efficacy, safety, and costs between neoadjuvant hypofractionated radiotherapy and conventionally fractionated radiotherapy for esophageal carcinoma. [2021]

3. Thailand pubmed.ncbi.nlm.nih.gov

Moderately hypofractionated conformal radiation treatment of thoracic esophageal carcinoma. [2019]

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

High-dose radiation therapy alone by moderate hypofractionation for patients with thoracic esophageal squamous cell carcinoma. [2022]

5. United States 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. [2018]

6. China 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]. [2023]

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

Hyaluronic Acid Spacer for Hypofractionated Prostate Radiation Therapy: A Randomized Clinical Trial. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Hypofractionated Radiotherapy in Oesophageal Cancer for Patients Unfit for Systemic Therapy: A Retrospective Single-Centre Analysis. [2020]

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

Chemoradiotherapy of esophageal carcinoma. [2022]