Chemoradiotherapy for Esophageal Cancer

(PaRCUS Trial)

Overseen By Amy Abel

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AHS Cancer Control Alberta

Disqualifiers: Previous chest radiotherapy, Active malignancies, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding two chemotherapy drugs, carboplatin and paclitaxel, to radiation therapy can ease swallowing problems and improve quality of life for individuals with esophageal cancer that cannot be surgically removed. The researchers aim to determine if this combination treatment is more effective than radiation alone. Suitable participants are those who struggle to eat solids due to their cancer and are not eligible for surgery. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 this trial's treatments are likely to be safe?

Research has shown that using carboplatin and paclitaxel together is generally safe and well-tolerated for people with esophageal cancer. Studies indicate that this treatment can be effective with few serious side effects, and patients often respond positively to this combination.

External beam radiation, another part of the treatment, is also considered safe. Research suggests that even older patients can undergo this treatment without major problems. Over time, improvements have made this method more effective and easier for patients to handle.

Overall, both treatments have a track record of safety. However, like any treatment, risks may still exist, so discussing these with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for esophageal cancer?

Researchers are excited about the combination of carboplatin, paclitaxel, and external beam radiation for esophageal cancer because it offers a potentially more effective approach by integrating chemotherapy and radiation. Unlike traditional treatments that often rely on surgery alone or in conjunction with chemotherapy, this method synchronizes chemotherapy with radiation, which may enhance cancer cell death and improve outcomes. The use of carboplatin and paclitaxel, which are given intravenously, allows for a targeted attack on cancer cells while radiation therapy is being administered, potentially reducing the tumor size more efficiently. This concurrent approach could lead to better survival rates and a more manageable treatment regimen for patients.

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

Research has shown that adding carboplatin and paclitaxel to radiation therapy can help treat esophageal cancer that cannot be surgically removed. In this trial, participants will receive chemotherapy with concurrent radiation, administering carboplatin and paclitaxel intravenously alongside radiation therapy. Studies have found that this combination can improve survival rates, particularly for squamous cell carcinoma, a type of esophageal cancer. Paclitaxel has effectively treated advanced cases with few side effects. Administering these drugs with radiation once a week has yielded positive results. Specifically, one study reported a median survival of 9 months, with 43% of patients surviving at least a year. Overall, this treatment has shown promise in aiding patients with this challenging condition. ^{2 6 7 8 9}

Who Is on the Research Team?

Marc Kerba, MD

Principal Investigator

403 521 3164

Are You a Good Fit for This Trial?

This trial is for adults with advanced esophageal cancer who can eat some solids, have a decent performance status, and proper organ function. They must start treatment within two weeks of consent, not be pregnant or breastfeeding, use effective contraception, and cannot have had previous chest radiation or chemotherapy for esophageal cancer.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

My esophageal cancer has been confirmed by a biopsy.

My condition cannot be cured due to its advanced stage or other health issues.

Exclusion Criteria

I have had radiation therapy to my chest before.

I have more than one type of cancer at the same time.

I cannot undergo certain treatments due to my health condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Carboplatin and paclitaxel chemotherapy on Days 1 and 8 concurrent with external beam radiation therapy of 30Gy/10 fractions over two weeks

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and quality of life improvements after treatment

6 months

Visits at 3 and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin and Taxol (paclitaxel)
• External Beam Radiation

Trial Overview The study tests if adding carboplatin and paclitaxel (chemotherapy drugs) to external beam radiation improves swallowing difficulties and life quality in patients with inoperable esophageal cancer compared to radiation alone.

How Is the Trial Designed?

Group I: Chemotherapy with Concurrent Radiation Experimental Treatment 2 Interventions

Carboplatin and paclitaxel will be administered intravenously on Days 1 and 8 while radiation therapy is administered

Carboplatin and Taxol (paclitaxel) is already approved in United States, European Union for the following indications:

Approved in United States as Carboplatin and Paclitaxel for:

• Non-small cell lung cancer
• Ovarian cancer
• Cervical cancer
• Endometrial cancer
• Thymoma or thymic carcinoma

Approved in European Union as Carboplatin and Paclitaxel for:

• Lung cancer
• Ovarian cancer
• Womb cancer
• Cervical cancer

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 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 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 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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8687861/

Chemoradiation with Weekly Paclitaxel and Carboplatin in ... Neoadjuvant chemoradiation (CRT) using paclitaxel and carboplatin has significantly improved the survival rates in carcinoma esophagus, especially in squamous ...

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... Paclitaxel has shown clinical activity in advanced esophageal malignancy with low toxicity.[13] The administration of paclitaxel and carboplatin once-a-week is ...

3. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-022-02190-4

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 ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e16033

Outcomes of neoadjuvant and definitive CROSS ... The best outcomes were seen in patients with SCC treated with neoadjuvant CROSS; this group had the highest OS (29 months), the lowest relapse rate (22%) and ...

5. 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 ...

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/14666040/

Preoperative chemotherapy for esophageal cancer with ... Paclitaxel-carboplatin combination is a safe and well-tolerated regimen for esophageal cancer with clinical response rates comparable to historical controls.

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.