Combination Chemotherapy + Radiation for Esophageal Cancer

Recruiting at 2 trial locations

Overseen By Theodore S Hong, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Cimetidine

Disqualifiers: Metastatic disease, Prior chemotherapy, Cardiac morbidity, 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: 13

Duration: 16 weeks

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take cimetidine during the study. You might need to switch to another similar medication before starting the trial.

What data supports the effectiveness of the treatment Combination Chemotherapy + Radiation for Esophageal Cancer?

Research shows that combining chemotherapy drugs like paclitaxel and carboplatin with radiation therapy can improve outcomes for patients with esophageal cancer. Studies have found that this combination can be effective in treating both advanced and localized forms of the disease. ^{1 2 3 4 5}

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

Studies have shown that combining chemotherapy drugs like carboplatin and paclitaxel with radiation therapy is generally safe for treating esophageal cancer, though some patients may experience side effects like neutropenia (low white blood cell count) and esophagitis (inflammation of the esophagus). ^{3 6 7 8 9}

What makes the combination chemotherapy and radiation treatment for esophageal cancer unique?

This treatment is unique because it combines multiple chemotherapy drugs, including carboplatin, FOLFOX, liposomal irinotecan, and paclitaxel, with radiation therapy, which is not a standard combination. The inclusion of newer agents like liposomal irinotecan and the specific combination of these drugs with radiation therapy may offer promising antitumor activity and better therapy tolerance. ^{3 10 11 12 13}

What is the purpose of this trial?

In this research study, is studying how Liposomal Irinotecan in combination with the standard of care interventions FOLFOX, carboplatin paclitaxel, and radiation therapy affect gastroesophageal junction or esophagogastric cancer This research study involves the following study intervention: - Liposomal irinotecan

Research Team

Theodore S Hong, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adults over 18 with a specific type of esophageal or gastroesophageal junction cancer, confirmed by pathology. They must have an ECOG performance status ≤1 (which means they are fully active or restricted in physically strenuous activity but can do light work), a life expectancy over 3 months, and adequate organ/marrow function. Women who can bear children need a negative pregnancy test and agree to use contraception during the study.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document.

absolute neutrophil count ≥ 1,500 cells/mm3

My organs and bone marrow are working well.

Exclusion Criteria

I am allergic to certain chemotherapy drugs like 5-fluorouracil, irinotecan, or oxaliplatin.

I have received treatments like chemotherapy or radiation for my esophagogastric cancer.

I am not taking cimetidine but can use other stomach acid reducers.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FOLFOX with nal-IRI for eight two-week cycles (16 weeks total)

16 weeks

8 visits (in-person)

Chemoradiation

Participants receive chemoradiation with proton or photon radiation therapy concurrent with weekly Paclitaxel and Carboplatin

5 weeks

5 visits (in-person)

Surgery

Participants undergo surgery following chemoradiation

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Carboplatin
• FOLFOX/ nal-IRI
• Liposomal irinotecan
• Paclitaxel
• Proton Radiation Therapy

Trial Overview The trial tests Liposomal Irinotecan combined with standard treatments: FOLFOX (a chemotherapy regimen), carboplatin, paclitaxel, and radiation therapy on patients with gastroesophageal junction or esophagogastric cancer. The goal is to see how this combination affects their cancer.

Participant Groups

Group I: FOLFOX/ nal-IRI Experimental Treatment 4 Interventions

Treatment will be administered on an outpatient basis. * FOLFOX with nal-IRI for eight two-week cycles (16 weeks total) * Chemoradiation with proton or photon radiation therapy concurrent with weekly Paclitaxel and Carboplatin for 5 weeks * Surgery

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?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Ipsen

Industry Sponsor

Trials

358

Recruited

74,600+

David Loew

Ipsen

Chief Executive Officer since 2020

BA in Business Administration and MBA from the University of St. Gallen, Switzerland

Sandra Silvestri

Ipsen

Chief Medical Officer since 2023

MD, PhD

Findings from Research

In a phase II trial involving 24 patients with resectable esophageal carcinoma, the combination of neoadjuvant therapy using paclitaxel, carboplatin, 5-fluorouracil, and conformal radiotherapy resulted in a 57% pathologic complete response rate, indicating significant effectiveness in shrinking tumors before surgery.

The treatment showed a median overall survival of 31 months and a disease-free survival rate of 57% at 3 years, although some patients experienced significant side effects, including esophagitis and hypotension, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemoradiotherapy for esophageal cancer using weekly Paclitaxel and Carboplatin plus infusional 5-Fluorouracil. Gannett, DE., Wolf, RF., Takahashi, GW., et al.[2022]

A phase II trial involving 49 patients with localized esophageal cancer showed that a combined neoadjuvant therapy of paclitaxel, carboplatin, continuous low-dose 5-fluorouracil, and radiation therapy was feasible and had moderate toxicity, primarily causing leukopenia (65%) and esophagitis (31%).

The treatment demonstrated promising efficacy, with 46% of evaluable patients achieving pathologic complete remission and 30% having only microscopic residual disease, indicating that this regimen could be a viable option for patients before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative combined modality therapy with paclitaxel, carboplatin, prolonged infusion 5-fluorouracil, and radiation therapy in localized esophageal cancer: preliminary results of a Minnie Pearl Cancer Research Network phase II trial. Meluch, AA., Hainsworth, JD., Gray, JR., et al.[2015]

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 72 patients with locally advanced esophageal squamous cell carcinoma, those receiving intensity-modulated radiotherapy (IMRT) combined with chemotherapy (liposomal paclitaxel and cisplatin) had significantly better overall survival (29.7 months) and progression-free survival (14.0 months) compared to those receiving IMRT alone (12.9 months and 6.5 months, respectively).

The inclusion of chemotherapy was identified as an independent predictor of improved survival outcomes, and both treatment approaches were well-tolerated by patients, suggesting a promising combination for enhancing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent liposomal paclitaxel and cisplatin chemotherapy improved outcomes for locally advanced esophageal squamous cell carcinoma treated with intensity-modulated radiotherapy. Liu, S., Ren, SN., Ding, WX., et al.[2022]

Pre-operative chemotherapy with Paclitaxel-Carboplatin followed by adjuvant immunotherapy using Nivolumab has significantly improved the management of locally advanced esophageal cancer, which historically has a poor prognosis.

Current trials are exploring the effectiveness of immunotherapy for non-operable esophageal cancers, while strategies like dose escalation and combining pre-operative chemo-radiotherapy with trastuzumab have not shown benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[News in gastrointestinal radiotherapy: The esophageal cancer]. Quéro, L., Besnard, C., Guillerm, S., et al.[2022]

In a study of 28 patients with unresectable or recurrent esophageal squamous cell carcinoma (ESCC), the combination of S-1 and paclitaxel (S1/PTX) showed a response rate of 14.8%, with a median overall survival time of 306 days, indicating some clinical efficacy in this difficult-to-treat population.

While S1/PTX was generally well-tolerated, severe neutropenia occurred in 13 patients, highlighting the need for monitoring blood counts during treatment, although most non-hematological side effects were mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Trial of S-1 and Paclitaxel in Unresectable or Postoperative Recurrent Esophageal Squamous Cell Carcinoma Pretreated by Fluorouracil, Cisplatin, and Docetaxel Chemotherapy. Nakajima, Y., Kawada, K., Tokairin, Y., et al.[2019]

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]

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 57 patients with locally advanced esophageal cancer, concurrent chemoradiotherapy using carboplatin/paclitaxel resulted in significantly better overall survival (56.1% at 3 years) compared to cisplatin/irinotecan (19.7% at 3 years).

Both treatment regimens had similar levels of acute toxicities, indicating that carboplatin/paclitaxel is not only more effective but also well-tolerated in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin/Irinotecan versus carboplatin/paclitaxel as definitive chemoradiotherapy for locoregionally advanced esophageal cancer. Ruppert, BN., Watkins, JM., Shirai, K., et al.[2018]

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]

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 study of 364 patients with esophageal cancer, those treated with the carboplatin/paclitaxel regimen experienced less weight loss during treatment compared to those receiving cisplatin/5-fluorouracil, indicating a potentially better tolerability of the former regimen.

Carboplatin/paclitaxel also resulted in a higher rate of pathologic complete response (29.6%) compared to cisplatin/5-FU (21.8%), suggesting it may be more effective in achieving tumor response, although overall survival and progression-free survival rates were similar between the two regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin/5-Fluorouracil (5-FU) Versus Carboplatin/Paclitaxel Chemoradiotherapy as Definitive or Pre-Operative Treatment of Esophageal Cancer. Steber, C., Hughes, RT., McTyre, ER., et al.[2021]

Combined chemoradiotherapy remains the standard treatment for nonsurgical esophageal cancer, with pathologic complete responses observed in 20% to 40% of patients and a 5-year survival rate of 30% to 35%.

Newer targeted therapies are being developed to enhance treatment efficacy by combining them with traditional chemotherapy and radiation, although increasing radiation doses alone has not improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the treatment of esophageal cancer. Ilson, DH.[2019]

References

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

Neoadjuvant chemoradiotherapy for esophageal cancer using weekly Paclitaxel and Carboplatin plus infusional 5-Fluorouracil. [2022]

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

Preoperative combined modality therapy with paclitaxel, carboplatin, prolonged infusion 5-fluorouracil, and radiation therapy in localized esophageal cancer: preliminary results of a Minnie Pearl Cancer Research Network phase II trial. [2015]

3. 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]

4. China pubmed.ncbi.nlm.nih.gov

Concurrent liposomal paclitaxel and cisplatin chemotherapy improved outcomes for locally advanced esophageal squamous cell carcinoma treated with intensity-modulated radiotherapy. [2022]

5. France pubmed.ncbi.nlm.nih.gov

[News in gastrointestinal radiotherapy: The esophageal cancer]. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

A Pilot Trial of S-1 and Paclitaxel in Unresectable or Postoperative Recurrent Esophageal Squamous Cell Carcinoma Pretreated by Fluorouracil, Cisplatin, and Docetaxel Chemotherapy. [2019]

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

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

8. 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]

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

Cisplatin/Irinotecan versus carboplatin/paclitaxel as definitive chemoradiotherapy for locoregionally advanced esophageal cancer. [2018]

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]

11. 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]

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

Cisplatin/5-Fluorouracil (5-FU) Versus Carboplatin/Paclitaxel Chemoradiotherapy as Definitive or Pre-Operative Treatment of Esophageal Cancer. [2021]

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

New developments in the treatment of esophageal cancer. [2019]