Combination Chemotherapy + Radiation for Esophageal Cancer

Recruiting at 2 trial locations

Overseen By Jennifer Wo, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a new combination of chemotherapy and radiation can treat gastroesophageal junction or esophagogastric cancer. It uses Liposomal Irinotecan (a form of chemotherapy) alongside standard treatments like FOLFOX, carboplatin, paclitaxel, and radiation. Researchers aim to determine if this combination is more effective and how it impacts the cancer. Individuals with confirmed advanced gastroesophageal cancer, who have not received prior treatment for this cancer and meet specific organ function criteria, may be suitable for the trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Studies have shown that the combination of FOLFOX and liposomal irinotecan (nal-IRI) is generally well-tolerated by patients. Research indicates that the FOLFOX regimen, a mix of chemotherapy drugs, usually has manageable side effects. One study found nal-IRI, when used with other drugs, to be safe for patients, with manageable side effects.

When used together, the FOLFOX/nal-IRI combination aims to improve cancer treatment without causing severe side effects. Data from previous patients suggest this combination is promising in terms of safety. While some side effects can occur, they are generally not severe enough to stop treatment.

Overall, evidence supports the safety of this treatment combination for human use, based on previous studies and patient experiences. However, discussing any concerns with a healthcare provider before joining a trial is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination treatment for esophageal cancer because it integrates a novel approach using FOLFOX with nal-IRI, along with chemoradiation, to enhance effectiveness. This regimen combines multiple chemotherapy drugs, including liposomal irinotecan, which may improve drug delivery and absorption compared to standard treatments. By incorporating proton or photon radiation therapy alongside weekly Paclitaxel and Carboplatin, this approach aims to maximize cancer cell destruction while minimizing damage to surrounding healthy tissues. This comprehensive strategy offers the potential for improved outcomes over traditional chemotherapy and radiation methods.

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

Research has shown that a treatment combining liposomal irinotecan with fluorouracil and leucovorin, known as nal-IRI/FL, yields promising results for certain cancers. In earlier studies, this treatment helped shrink tumors and slow disease progression. Another treatment using oxaliplatin with leucovorin and fluorouracil has demonstrated strong anti-cancer effects and is generally well-tolerated by patients. In this trial, participants will receive a combination of FOLFOX (a type of chemotherapy) with nal-IRI, which might be effective for cancers of the gastroesophageal junction or esophagogastric area. Although more research is needed to confirm these results, the current evidence is encouraging. ^{1 4 6 7 8}

Who Is on the Research Team?

Jennifer Wo, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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 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]

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]

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 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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11889194/

The efficacy and safety of FOLFOX therapy for advanced ... First-line FOLFOX treatment is suitable for patients with advanced ESCC. However, FOLFOX has shown limited efficacy as a later-line treatment.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12049620/

Real-world outcomes of fluorouracil-based second-line ... Our study aimed to evaluate the real-world efficacy and safety of 5-FU-based chemotherapy for BTC patients who had progressed after gemcitabine-based treatment.

3. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1638606/full

Liposomal irinotecan with fluorouracil and leucovorin as ... Introduction: The combination of liposomal irinotecan with fluorouracil and leucovorin (Nal-IRI/FL) has shown efficacy in phase II trials ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03861702

Liposomal Irinotecan in Combination With Oxaliplatin ... This is a phase II, single-arm, open-label, clinical study to investigate the efficacy and tolerability of a combination of liposomal irinotecan (nal-IRI) ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)54944-4/fulltext

Phase II trial of oxaliplatin, leucovorin and fluorouracil in ... Conclusions: The combination of oxaliplatin, leucovorin, and fluorouracil shows significant anti-tumor activity and a favorable toxicity profile in patients ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)00388-5/fulltext

P-190 NALIRIFOX (iposomal irinotecan + 5-fluorouracil/ ... NALIRIFOX regimen in NAPOLI 3 resulted in significantly improved OS compared to FOLFOX in a RW clinical practice setting, suggesting a clinically meaningful ...

7. thelancet.com thelancet.com/journals/langas/article/PIIS2468-1253(24)00119-5/fulltext

Nanoliposomal irinotecan and fluorouracil plus leucovorin ... Here, we report the results of a randomised phase 2 trial investigating the efficacy and safety of nanoliposomal irinotecan and fluorouracil ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419609063

First-line treatment of metastatic colorectal cancer with ... This simplified FOLFOXIRI combination can be delivered easily in outpatient settings, with manageable toxic effects, and has very promising antitumor activity.