Chemoradiotherapy + Surgery for Esophageal Cancer

(NEEDS Trial)

Recruiting at 14 trial locations

Overseen By Magnus Nilsson, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Karolinska University Hospital

Disqualifiers: Metastatic cancer, Unresectable tumor, Organ impairment, 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)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 6

Duration: 5-8 weeks

1020 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for esophageal cancer, specifically squamous cell carcinoma (SCC) that can be surgically removed. It aims to determine whether patients fare better with a combination of chemoradiotherapy (including drugs like Carboplatin and Cisplatin) and surgery, or with chemoradiotherapy alone, followed by surgery if cancer returns. The study will evaluate survival rates, quality of life, and eating ability one year after treatment. Suitable candidates for this trial have been diagnosed with locally advanced SCC of the esophagus that can be surgically treated. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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 to get a clear answer based on your specific situation.

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

Research shows that the treatments in this trial are generally well-tolerated, though they can cause some side effects.

For Carboplatin, studies indicate that when combined with Paclitaxel, most side effects are manageable. However, a significant number of patients, about 71% to 78%, may experience serious side effects.

Cisplatin, another drug in the trial, has shown varying results in response and survival rates. It is generally effective and tolerable, but severe reactions can occur, especially when combined with other drugs.

Oxaliplatin, although not approved in the U.S. for esophageal cancer, has been studied with other drugs. It has shown effectiveness, but reports indicate significant side effects that can increase over time.

These findings suggest potential benefits, but participants should be aware of the possibility of significant side effects with these treatments. Discuss any concerns with the trial team or a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial for esophageal cancer because it explores different combinations of chemoradiotherapy and surgery, offering tailored approaches based on patient response. Unlike the standard of care, which typically involves neoadjuvant chemoradiotherapy followed by surgery, this trial includes an experimental arm where surgery is reserved for cases with lingering or returning cancer after initial treatment. This approach not only reduces the need for immediate surgery but also tests a variety of chemotherapy regimens, like the FOLFOX regimen, which might offer more effective cancer control with potentially fewer side effects. By comparing these strategies, researchers hope to discover more flexible and effective treatment plans for patients.

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

In this trial, participants will join different treatment arms to evaluate the effectiveness of various chemoradiotherapy regimens for esophageal cancer. Research has shown that using carboplatin and paclitaxel together, as in the control arm, can significantly improve survival rates, with a 5-year survival rate of 31.4%. In the experimental arm, cisplatin is used, and studies have shown an average survival time of 22 months, with some patients living without the disease for over three years. Oxaliplatin, another drug in the experimental arm, has demonstrated that more than 80% of patients experience a noticeable reduction in cancer size. Overall, these treatments have shown promising results for managing advanced squamous cell carcinoma, a type of esophageal cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Magnus Nilsson, MD, PhD

Principal Investigator

Karolinska University Hospital

Florian Lordick, MD, PhD

Principal Investigator

Leipzig University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with a specific type of esophageal cancer (SCC) that hasn't spread beyond the local area. They must be in good physical condition, have organs functioning well, and women must not be pregnant or breastfeeding. Participants should use effective birth control and commit to following the study's procedures.

Inclusion Criteria

Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment

My esophagus cancer is confirmed and in an advanced stage but hasn't spread to distant organs.

Exclusion Criteria

I have been cancer-free for at least 5 years from a previous cancer.

My cancer has spread to distant parts of my body.

My throat cancer cannot be removed without taking out my voice box.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant chemoradiotherapy followed by esophagectomy or definitive chemoradiotherapy with surveillance and salvage esophagectomy as needed

5-8 weeks

Weekly visits for chemotherapy administration

Follow-up

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

5 years

Regular visits at 6, 12, 24, 36, and 60 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Esophagectomy
• Neoadjuvant radiotherapy
• Oxaliplatin

Trial Overview The NEEDS trial compares two approaches: one group receives chemotherapy plus radiotherapy before surgery, while another gets the same treatments but only has surgery if necessary later on. The focus is on survival rates, quality of life, and eating ability after treatment.

How Is the Trial Designed?

Group I: Experimental arm (B) Experimental Treatment 5 Interventions

Definitive chemoradiotherapy followed by surveillance, and esophagectomy only in case of residual or recurrent locoregional cancer. Radiotherapy: Two alternative schemes: 1. 1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy. 2. 2.0 Gy fractions five days per week in 25 fractions to a total dose of 50 Gy. Chemotherapy: Three alternative regimens: 1\. Platin-Taxane Regimen: Carboplatin AUC 2 + Paclitaxel 50mg/m2 on day 1 weekly during the full course of radiotherapy. 2a. Platinum-Fluoropyrimidine Regimen: Cisplatin 75mg/m2 weeks 1 and 5 + 5-fluorouracil 1000 mg/m2/day by continuous infusion weeks 1 and 5. 2b. FOLFOX: Oxaliplatin 85 mg/m2, calcium folinate 200 mg/m2 and 5-fluorouracil 400 mg/m2 weeks 1, 3 and 5 + 5-fluorouracil 800 mg/m2 by continuous infusion weeks 1, 3 and 5.

Group II: Control arm (A) Active Control 3 Interventions

Neoadjuvant chemoradiotherapy followed by esophagectomy. Radiotherapy: 1.8 Gy fractions 5 days per week in 23 fractions to a total dose of 41.4 Gy. Chemotherapy: Carboplatin AUC 2 + Paclitaxel 50mg/m2 weekly x 5 (day 1, 8, 15, 22, 29), starting on the first day of radiotherapy. Esophagectomy: Within 8 weeks of termination of chemoradiotherapy,

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?

Karolinska University Hospital

Lead Sponsor

Trials

509

Recruited

1,319,000+

The Swedish Research Council

Collaborator

Trials

159

Recruited

4,805,000+

University of Leipzig

Collaborator

Trials

219

Recruited

1,288,000+

Published Research Related to This Trial

This randomized phase II trial is comparing the efficacy and toxicity of two chemoradiation regimens, OXCAP-RT and CarPac-RT, in patients with resectable oesophageal adenocarcinoma, with a primary focus on achieving a pathological complete response rate (pCR) after treatment.

The study involves 76 patients and aims to determine which regimen is more effective and safer, potentially leading to a future phase III trial against the current standard neo-adjuvant chemotherapy in the UK.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NEOSCOPE: a randomised Phase II study of induction chemotherapy followed by either oxaliplatin/capecitabine or paclitaxel/carboplatin based chemoradiation as pre-operative regimen for resectable oesophageal adenocarcinoma. Mukherjee, S., Hurt, CN., Gwynne, S., et al.[2023]

Preoperative chemotherapy or chemoradiation is beneficial for patients with operable esophageal cancer, particularly for those with more advanced stages of the disease.

Further research is needed to explore modern chemotherapy combinations and to develop methods for predicting patient outcomes from neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemotherapy or chemoradiotherapy for locally advanced esophageal cancer. Smithers, BM., Thomson, I.[2022]

Cis-platinum is a highly effective chemotherapy agent used for various cancers, including testicular, ovarian, and bladder cancers, but it can cause dose-limiting kidney toxicity.

Recent advancements have identified methods to mitigate these toxic effects, allowing for the safe use of higher doses (up to 200 mg/m2) that significantly improve outcomes in patients with poor prognostic testicular cancer compared to standard doses (100 mg/m2).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology and clinical applications of cis-platinum. Javadpour, N.[2019]

The combination of oxaliplatin, docetaxel, and capecitabine (ODC) with radiation therapy showed a high pathologic complete response (pCR) rate of 49% in patients with resectable esophageal cancer, indicating its efficacy as a preoperative treatment.

The treatment was found to be relatively safe, with no dose-limiting toxicities in the initial phase and manageable side effects, suggesting it can be administered effectively within 8 weeks before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of preoperative oxaliplatin, docetaxel, and capecitabine with concurrent radiation therapy in localized carcinoma of the esophagus or gastroesophageal junction. Spigel, DR., Greco, FA., Meluch, AA., et al.[2018]

In a study of 11 patients with advanced oesophageal cancer, carboplatin showed a partial response in 9% of patients and minor responses in 2 cases, indicating some level of antitumor activity.

Carboplatin was well tolerated, with only one case of reversible myelosuppression reported, and no nephrotoxicity or vomiting, suggesting it may be a safer alternative to cisplatin in chemotherapy regimens for oesophageal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in the treatment of oesophageal cancer. Mannell, A., Winters, Z.[2014]

In a study of 96 esophageal cancer patients treated with a neoadjuvant chemoradiotherapy regimen, there was a significant increase in postoperative complications such as pneumonia (51.0% vs. 27.1%), pleural effusion (24.0% vs. 12.5%), and arrhythmia (34.4% vs. 20.4%) compared to patients who underwent surgery alone.

Despite the higher rates of cardiopulmonary complications in the neoadjuvant CRT group, there were no differences in the length of hospital or intensive care unit stays, nor in short-term mortality, indicating that while neoadjuvant CRT may increase certain risks, it does not affect overall survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of neoadjuvant chemoradiotherapy on postoperative course after curative-intent transthoracic esophagectomy in esophageal cancer patients. Bosch, DJ., Muijs, CT., Mul, VE., et al.[2022]

In a safety analysis of 6 patients with locally advanced esophageal cancer, the combination of pemetrexed, carboplatin, and radiation followed by surgery showed a favorable safety profile, with only one patient experiencing a severe adverse event (grade 4 neutropenia).

The treatment resulted in promising outcomes, with one patient achieving a complete pathologic response and three showing partial responses, indicating potential efficacy that warrants further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed, Carboplatin, and Concomitant Radiation followed by Surgery for Locally Advanced Esophageal Cancer: Results of a Planned Interim Toxicity Analysis of North Central Cancer Treatment Group Study N044E. Katipamula, R., Jatoi, A., Foster, NR., et al.[2021]

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]

The CROSS trial is a multicenter, randomized phase III clinical trial involving 350 patients, designed to compare the effectiveness of neoadjuvant chemoradiotherapy followed by surgery against surgery alone for treating potentially curable esophageal cancer.

The trial aims to assess various outcomes, including median survival rates, quality of life, and the rate of complete R0 resections, to determine if the neoadjuvant treatment improves overall survival and locoregional control in patients with esophageal adenocarcinoma or squamous cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemoradiation followed by surgery versus surgery alone for patients with adenocarcinoma or squamous cell carcinoma of the esophagus (CROSS). van Heijl, M., van Lanschot, JJ., Koppert, LB., et al.[2022]

Neoadjuvant chemoradiotherapy with the paclitaxel plus platinum regimen significantly improves overall survival in patients with locoregional esophageal cancer compared to surgery alone, with a hazard ratio of 0.63 for the entire population.

In particular, this regimen is especially effective for patients with squamous cell carcinoma, showing a hazard ratio of 0.50, indicating a substantial reduction in the risk of death compared to surgery alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review and network meta-analysis: neoadjuvant chemoradiotherapy for locoregional esophageal cancer. Huang, TC., Hsu, CH., Lin, CC., et al.[2022]

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]

Neoadjuvant chemoradiotherapy (CTRT) is the standard treatment for locally advanced esophageal cancer, with the CROSS trial establishing the combination of radiotherapy with carboplatin and paclitaxel as the preferred regimen.

There is a need for further randomized trials to identify optimal chemotherapy and radiotherapy combinations, as well as to explore new multimodal strategies that include biological agents and immunotherapy for better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of different available chemotherapy regimens combined with radiotherapy for the neoadjuvant and definitive treatment of esophageal cancer. Tomasello, G., Ghidini, M., Barni, S., et al.[2018]

Esophageal cancer is rapidly increasing in the U.S. and is aggressive, with poor survival rates from traditional treatments like surgery or chemoradiation alone.

New trials at Memorial Sloan-Kettering Cancer Center are exploring the use of weekly paclitaxel/cisplatin and irinotecan/cisplatin, which may reduce gastrointestinal toxicity while maintaining efficacy, compared to traditional cisplatin/5-FU regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined modality therapy in esophageal cancer: the Memorial experience. Anderson, SE., Minsky, BD., Bains, M., et al.[2018]

Citations

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