Immunotherapy Combinations for Esophageal Cancer

Recruiting at 45 trial locations

Overseen By Reference Study ID Number: YO39609 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must not be taking: NSAIDs, Anticoagulants

Disqualifiers: Autoimmune disease, CNS metastases, others

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

Compensation: Varies

Number of Visits: 21

Duration: Up to 3-6 years

410 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that chronic therapy with certain anti-inflammatory or anti-platelet agents is not allowed, and treatment with anticoagulation agents like warfarin is excluded. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination for esophageal cancer?

Research shows that combining drugs like cisplatin and 5-fluorouracil (5-FU) can have a synergistic effect, meaning they work better together, in treating esophageal cancer. Additionally, immunotherapy drugs like nivolumab have been shown to improve survival rates in esophageal cancer patients when used with chemotherapy. ^{1 2 3 4 5}

Is the combination of immunotherapy and chemotherapy safe for esophageal cancer?

Studies have shown that combinations of drugs like 5-fluorouracil, cisplatin, paclitaxel, and oxaliplatin, often used with radiotherapy, have been evaluated for safety in esophageal cancer. While these treatments can be effective, they may also cause side effects, which vary among patients. It's important to discuss potential risks with your healthcare provider. ^{6 7 8 9 10}

How is the drug combination of 5-Fluorouracil, Atezolizumab, Cisplatin, Oxaliplatin, and Tiragolumab unique for esophageal cancer?

This drug combination is unique because it includes Atezolizumab and Tiragolumab, which are immunotherapy drugs that help the immune system fight cancer, alongside traditional chemotherapy drugs like 5-Fluorouracil, Cisplatin, and Oxaliplatin. This approach aims to enhance the body's natural defenses against cancer, potentially offering a new option for patients with esophageal cancer. ^{1 2 4 11 12}

What is the purpose of this trial?

This trial tests a combination of chemotherapy and immunotherapy in patients with advanced gastric and esophageal cancers. It aims to see if this combination is safe and effective, especially for those who haven't responded to other treatments or haven't been treated before. Combination therapies involving chemotherapy and immunotherapy have shown promising results in initial clinical trials for cancer treatment.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

Adults with advanced gastric or gastroesophageal junction cancer, or esophageal cancer who have not had certain treatments. They must be in good physical condition (ECOG 0-1), expect to live at least 3 months, and agree to use contraception. Excluded are those with uncontrolled hypertension, recent severe infections, significant heart disease, autoimmune diseases, HIV/HBV/HCV infection, CNS metastases risk factors for bleeding disorders.

Inclusion Criteria

For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm;

Measurable disease (at least one target lesion) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm

Exclusion Criteria

Positive EBV viral capsid antigen IgM test at screening

Positive test for human immunodeficiency virus (HIV) at screening

Active hepatitis B virus (HBV) or hepatitis C (HCV) infection

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive immunotherapy-based treatment combinations, including atezolizumab with various agents, depending on the cohort and arm

Up to 3-6 years

Visits every 21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 to 120 days after last dose

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if they progress on initial treatment

Long-term

Treatment Details

Interventions

• 5-Fluorouracil (5-FU)
• Atezolizumab
• Cisplatin
• Leucovorin
• Linagliptin
• Oxaliplatin
• Paclitaxel
• Ramucirumab
• Tiragolumab

Trial Overview The trial is testing combinations of immunotherapy and chemotherapy in patients with advanced gastric or esophageal cancers. It includes drugs like Atezolizumab and Tiragolumab alongside standard chemotherapies such as Cisplatin and Paclitaxel. Patients will be randomly assigned to different treatment groups.

Participant Groups

Group I: 2L-4: Atezo + Linagliptin (Gastric Cancer) Experimental Treatment 2 Interventions

Participants in the 2L-4 Gastric Cancer arm received atezolizumab in combination with linagliptin. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.

Group II: 2L-3: Atezo + BL-8040 (Gastric Cancer) Experimental Treatment 2 Interventions

Participants in the 2L-3 Gastric Cancer arm received atezolizumab in combination with BL-8040. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.

Group III: 2L-2: Atezo + PEGPH20 (Gastric Cancer) Experimental Treatment 2 Interventions

Participants in the 2L-2 Gastric Cancer arm received atezolizumab in combination with PEGylated recombinant human hyaluronidase (PEGPH20). Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.

Group IV: 2L-1: Atezo + Cobi (Gastric Cancer) Experimental Treatment 2 Interventions

Participants in the 2L-1 Gastric Cancer arm received atezolizumab in combination with cobimetinib. Enrollment completed as of October 2019.

Group V: 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer) Experimental Treatment 5 Interventions

Participants in the 1L-A Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab plus cobimetinib. No longer enrolling participants as of June 2018.

Group VI: 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer) Experimental Treatment 5 Interventions

Participants in the 1L-A2 Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab during cycles 1 and 2 followed by atezolizumab plus cobimetinib during cycles 3 and beyond. No longer enrolling participants as of June 2018.

Group VII: 1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort) Experimental Treatment 2 Interventions

Participants in the 1L-3 Esophageal Cancer arm will receive atezolizumab + tiragolumab treatment. Participants from the cisplatin + 5-FU esophageal cancer cohort arm may be permitted to enroll in this arm if they progress after receiving chemotherapy.

Group VIII: 1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort) Experimental Treatment 3 Interventions

Participants in the 1L-2 Esophageal Cancer arm will receive atezolizumab in combination with chemotherapy.

Group IX: 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort) Experimental Treatment 4 Interventions

Participants in the 1L-1 Esophageal Cancer arm will receive atezolizumab in combination with tiragolumab and chemotherapy.

Group X: 2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer) Active Control 2 Interventions

Participants in the 2L Gastric Cancer Control arm received ramucirumab plus paclitaxel. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.

Group XI: 1L-Control: mFOLFOX6 (Gastric Cancer) Active Control 3 Interventions

Participants in the 1L Gastric Cancer Control arm will receive modified FOLFOX6 (mFOLFOX6) treatment consisting of 5-fluorouracil (5-FU), leucovorin (folinic acid), and oxaliplatin. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria. No longer enrolling participants as of June 2018.

Group XII: 1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort) Active Control 2 Interventions

Participants in the 1L-Control Eophageal Cancer arm will receive chemotherapy.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

BioLineRx, Ltd.

Industry Sponsor

Trials

24

Recruited

2,200+

Halozyme Therapeutics

Industry Sponsor

Trials

47

Recruited

3,400+

Findings from Research

Nimotuzumab (h-R3) showed a weak inhibitory effect on the proliferation of human esophageal squamous cell carcinoma (ESCC) EC1 cells, with a maximum inhibition rate of only 10.10% after 48 hours, indicating limited efficacy as a standalone treatment.

Combining h-R3 with chemotherapeutic agents like cisplatin or fluorouracil did not significantly enhance the inhibition of cell growth or increase apoptosis rates compared to the chemotherapeutic agents alone, suggesting that h-R3 may not provide additional benefits in treating ESCC in vitro.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nimotuzumab with cisplatin or fluorouracil on human esophageal squamous cell carcinoma EC1 cells. Ji, YH., Yang, XY., Wu, JQ., et al.[2019]

The combination of nivolumab (an anti-PD-1 antibody) with irinotecan and a fluoropyrimidine showed a disease control rate of 73.3% in 15 patients with advanced unresectable gastroesophageal cancers, indicating potential efficacy in this challenging patient population.

The treatment was generally feasible, with a median progression-free survival of 7 months and overall survival of 13.3 months, although 33% of patients experienced dose delays or adjustments primarily due to fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in Combination with Irinotecan and 5-Fluorouracil (FOLFIRI) for Refractory Advanced Gastroesophageal Cancer. Rogers, JE., Xiao, L., Trail, A., et al.[2023]

Nivolumab and pembrolizumab, both PD-1 inhibitors, have shown significant improvements in overall survival (OS) for patients with esophageal carcinoma, particularly in combination with chemotherapy or ipilimumab, based on multiple landmark trials.

In the second-line treatment setting, monotherapy with nivolumab, pembrolizumab, and other PD-1 inhibitors also demonstrated improved OS compared to traditional chemotherapy, highlighting the effectiveness of immunotherapy in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in Squamous Cell Cancer of the Esophagus. Thuss-Patience, P., Stein, A.[2022]

In a phase II study involving 50 patients with advanced oesophageal cancer, the addition of cetuximab to the standard treatment of 5-FU/cisplatin/docetaxel (TPF) and chemoradiotherapy resulted in a clinical complete response (cCR) rate of 12% and an overall response rate of 54%.

The median overall survival for patients who underwent complete surgical resection was significantly longer at 42.1 months compared to 24.9 months for those who did not have surgery, indicating that achieving a complete resection is crucial for improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients. Alsina, M., Rivera, F., Ramos, FJ., et al.[2019]

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 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 Phase II study involving 64 patients with locally advanced esophageal squamous cell carcinoma, the combination of the PD-L1 inhibitor socazolimab with nab-paclitaxel and cisplatin showed promising efficacy, achieving a major pathological response (MPR) rate of 69.0% compared to 62.1% in the control group, although this difference was not statistically significant.

The socazolimab combination therapy resulted in a significantly higher rate of complete tumor downstaging (ypT0) at 37.9% compared to 3.5% in the control group, indicating a potential benefit in tumor reduction without increasing surgical complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing a PD-L1 inhibitor plus chemotherapy to chemotherapy alone in neoadjuvant therapy for locally advanced ESCC: a randomized Phase II clinical trial : A randomized clinical trial of neoadjuvant therapy for ESCC. Li, Y., Zhou, A., Liu, S., et al.[2023]

In a study of 30 patients with resectable esophageal squamous cell carcinoma, a chemotherapy regimen combining 5-fluorouracil, cisplatin, and interferon-alpha showed promising results, with a median overall survival of 26.3 months.

The treatment led to a complete pathological response in 4 out of 23 patients who underwent esophagectomy, indicating significant effectiveness, although there was one toxic death due to esophageal perforation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of neoadjuvant cisplatin, 5-fluorouracil and interferon-alpha in operable squamous cell carcinoma of the esophagus. Bazarbashi, S., Abdelsalam, M., Amin, T., et al.[2013]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Nimotuzumab with cisplatin or fluorouracil on human esophageal squamous cell carcinoma EC1 cells. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Nivolumab in Combination with Irinotecan and 5-Fluorouracil (FOLFIRI) for Refractory Advanced Gastroesophageal Cancer. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Immunotherapy in Squamous Cell Cancer of the Esophagus. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

A pilot trial of combination cisplatin, 5-fluorouracil and interferon-alpha in the treatment of advanced esophageal carcinoma. [2017]

5. Greece pubmed.ncbi.nlm.nih.gov

Panitumumab in combination with modified docetaxel/cisplatin/5-fluorouracil as first-line treatment in gastric and gastroesophageal junction adenocarcinomas: a multicenter phase II study by the Hellenic Oncology Research Group. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer. [2018]

7. France pubmed.ncbi.nlm.nih.gov

A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients. [2019]

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

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

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Comparing a PD-L1 inhibitor plus chemotherapy to chemotherapy alone in neoadjuvant therapy for locally advanced ESCC: a randomized Phase II clinical trial : A randomized clinical trial of neoadjuvant therapy for ESCC. [2023]

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

A phase II trial of interferon alpha-2A, 5-fluorouracil, and cisplatin in patients with advanced esophageal carcinoma. [2019]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Phase II trial of neoadjuvant cisplatin, 5-fluorouracil and interferon-alpha in operable squamous cell carcinoma of the esophagus. [2013]