A Phase II/III Study of Peri-Operative Nivolumab and Ipilimumab in Patients With Locoregional Esophageal and Gastroesophageal Junction Adenocarcinoma

Plain English Summary

Nivolumab and Ipilimumab in Treating Patients With Esophageal and Gastroesophageal Junction Adenocarcinoma Undergoing Surgery is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Clinical Stage II Esophageal Adenocarcinoma AJCC v8, Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage III Esophageal Adenocarcinoma AJCC v8, Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8, Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8, Esophageal Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma. Tests the effectiveness of nivolumab and ipilimumab in combination with standard chemotherapy and radiation therapy for esophageal and gastroesophageal cancer before surgery. For patients with clinical stage II to IV esophageal or gastroesophageal adenocarcinoma who are undergoing surgery. Participation involves blood tests, IV treatments, and scans. Patients will receive nivolumab and ipilimumab, chemotherapy, and radiation therapy. Alternative treatments include standard chemotherapy and radiation therapy alone. The trial aims to enroll 278 participants.

Official Summary

This phase II/III trial studies the usefulness of treatment with nivolumab and ipilimumab in addition to standard of care chemotherapy and radiation therapy in patients with esophageal and gastroesophageal junction adenocarcinoma who are undergoing surgery. Immunotherapy with antibodies, such as nivolumab and ipilimumab, may remove the brake on the body's immune system and may interfere with the ability of tumor cells to grow and spread. Chemotherapy and radiation therapy may reduce the tumor size and the amount of normal tissue that needs to be removed during surgery. A combined treatment with nivolumab and ipilimumab, chemotherapy, and radiation therapy might be more effective in patients with esophageal and gastroesophageal junction adenocarcinoma who are undergoing surgery.

Who Can Participate

Here is what you need to know about eligibility for this trial. Age >= 18 years Histologically confirmed esophageal or gastroesophageal adenocarcinoma ECOG performance status 0-1 No prior chemotherapy, radiation, or immunotherapy for this cancer This trial is studying Clinical Stage II Esophageal Adenocarcinoma AJCC v8, Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage III Esophageal Adenocarcinoma AJCC v8, Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8, Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8, Esophageal Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures the pathologic complete response and disease-free survival, which means patients will know if the treatment has successfully eliminated cancer cells and reduced the risk o The specific primary outcome measures are: Pathologic complete response (Step I) (Up to 5 weeks); Disease-free survival (DFS) (Step 2) (From the adjuvant treatment randomization assessed for up to 7 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill the treatment gap by exploring the combination of immunotherapy with standard treatments for esophageal and gastroesophageal cancer, potentially offering better outcomes. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Clinical Stage II Esophageal Adenocarcinoma AJCC v8, Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage III Esophageal Adenocarcinoma AJCC v8, Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8, Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8, Esophageal Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, where improved treatment options are needed.

Investor Insight

The large market size and competitive landscape indicate a high approval probability for this innovative treatment approach. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you meet the eligibility criteria and understand the potential benefits and risks. Participation involves regular blood tests, IV treatments, and scans. You will receive nivolumab and ipilimumab, chemotherapy, and radiation therapy. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 278 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo collection of blood sample
• DRUG: Carboplatin — Given IV
• PROCEDURE: Computed Tomography — Undergo CT scan
• BIOLOGICAL: Ipilimumab — Given IV
• BIOLOGICAL: Nivolumab — Given IV

Primary Outcomes

• Pathologic complete response (Step I) (Up to 5 weeks)
• Disease-free survival (DFS) (Step 2) (From the adjuvant treatment randomization assessed for up to 7 years)

Secondary Outcomes

• Incidence of adverse events (Up to 7 years)
• Overall survival (From the time of first randomization up to 7 years)
• DFS (From the time of first randomization up to 7 years)

Full Eligibility Criteria

Inclusion Criteria:

* STEP 1 RANDOMIZATION: Patients must be age \>= 18 years
* STEP 1 RANDOMIZATION: Patients must have histologically confirmed T1N1-3M0 or T2-3N0-2M0 esophageal or gastroesophageal junctional adenocarcinoma (Siewert I and II)
* STEP 1 RANDOMIZATION: Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* STEP 1 RANDOMIZATION: Patents must be deemed a surgical candidate by a thoracic surgeon, surgical oncologist, or surgeon who is qualified to perform an esophagectomy
* STEP 1 RANDOMIZATION: Absolute neutrophil count \>= 1,500/mcL (within less than or equal to 14 days prior to randomization)
* STEP 1 RANDOMIZATION: Platelets \>= 100,000/mcL (within less than or equal to 14 days prior to randomization)
* STEP 1 RANDOMIZATION: Total bilirubin =\< institutional upper limit of normal (ULN) (within less than or equal to 14 days prior to randomization)
* STEP 1 RANDOMIZATION: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (within less than or equal to 14 days prior to randomization)
* STEP 1 RANDOMIZATION: Serum creatinine =\< 1.5 x institutional ULN (within less than or equal to 14 days prior to randomization)
* STEP 1 RANDOMIZATION: Hemoglobin (Hgb) \>= 9 g/dL (within less than or equal to 14 days prior to randomization)
* STEP 1 RANDOMIZATION: Leukocytes \>= 3,000/mm\^3 (within less than or equal to 14 days prior to randomization)
* STEP 1 RANDOMIZATION: Patients may not have received prior chemotherapy or radiation therapy for management for this malignancy
* STEP 1 RANDOMIZATION: Patients may not have received prior immunotherapy for management of this malignancy or for any other past malignancy
* STEP 1 RANDOMIZATION: Patients must have no contraindication to receiving either carboplatin or paclitaxel chemotherapy
* STEP 1 RANDOMIZATION: Patients must have no contraindication to receiving radiation therapy
* STEP 1 RANDOMIZATION: Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, must be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue disease, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome must be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies must be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
* STEP 1 RANDOMIZATION: Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
* STEP 1 RANDOMIZATION: Patient must NOT have previous or concurrent malignancy. Exceptions are made for patients who meet any of the following conditions:

  * Non-melanoma skin cancer, in situ cervical cancer, superficial bladder cancer, or breast cancer in situ OR
  * Prior malignancy completely excised or removed and patient has been continuously disease free for \> 5 years OR
  * Date of last evidence of disease
* STEP 1 RANDOMIZATION: Patients must not have a condition requiring systemic treatment with either corticosteroids (\> 10 mg/day prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses =\< 10 mg/day prednisone equivalents are permitted in the absence of active autoimmune disease
* STEP 1 RANDOMIZATION: Patients must have adequate cardiac function including electrocardiogram (EKG) and echocardiogram for any patient with a history of congestive heart failure (CHF) or at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs
* STEP 1 RANDOMIZATION: For patients with evidence of uncontrolled CHF, myocardial infarction (MI), cardiomyopathy, or myositis, require a cardiac evaluation and clearance including lab tests a

Trial Locations

• Anchorage Associates in Radiation Medicine, Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC, Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC, Anchorage, Alaska, United States
• Alaska Women's Cancer Care, Anchorage, Alaska, United States
• Anchorage Oncology Centre, Anchorage, Alaska, United States
• Katmai Oncology Group, Anchorage, Alaska, United States
• Providence Alaska Medical Center, Anchorage, Alaska, United States
• Cancer Center at Saint Joseph's, Phoenix, Arizona, United States
• Mercy Hospital Fort Smith, Fort Smith, Arkansas, United States
• CHI Saint Vincent Cancer Center Hot Springs, Hot Springs, Arkansas, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Esophageal Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma
• Esophageal Squamous Cell Carcinoma
• Gastric Cancer
• Pancreatic Cancer
• Liver Cancer
• Colorectal Cancer
• Lung Cancer
• Head and Neck Cancer
• Stomach Cancer

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