Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Esophageal Neoplasms

Adenocarcinoma

Stomach Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Head and Neck Neoplasms

Esophageal Diseases

Esophageal Cancer

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Paclitaxel

Albumin-Bound Paclitaxel

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Ramucirumab

Lexatumumab

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Tubulin Modulators

Antimitotic Agents

Immunologic Factors

Immune Checkpoint Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive nivolumab IV over 30 minutes on day 1 of each cycle, ramucirumab IV over 30-60 minutes on days 1 and 15 of each cycle, and paclitaxel IV over 30 minutes on days 1, 8 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and MRI throughout the study. Patients may also optionally undergo blood sample collection on study.

Patients receive ramucirumab IV over 30-60 minutes on days 1 and 15 of each cycle and paclitaxel IV over 30 minutes on days 1, 8 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and MRI throughout the study. Patients may also optionally undergo blood sample collection on study.

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Questionnaire Administration

Site Public Contact

Bryan A. Faller

Deborah W. Wilbur

Anwaar Saeed

This phase II/III trial compares the addition of nivolumab to the usual treatment of paclitaxel and ramucirumab to paclitaxel and ramucirumab alone in treating patients with gastric or esophageal adenocarcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Adding nivolumab to ramucirumab and paclitaxel may work better to treat patients with advanced stomach or esophageal cancer.

PRIMARY OBJECTIVES:

I. To assess whether progression-free survival (PFS) is sufficiently improved in participants randomized to nivolumab + paclitaxel + ramucirumab compared to those randomized to paclitaxel + ramucirumab to warrant a phase III study with overall survival (OS) as the primary endpoint. (Phase II) II. To compare OS in participants randomized to nivolumab + paclitaxel + ramucirumab versus those randomized to paclitaxel + ramucirumab. (Phase III)

SECONDARY OBJECTIVES:

I. To compare PFS between those randomized to nivolumab + paclitaxel + ramucirumab versus those randomized to paclitaxel + ramucirumab. (Phase III) II. To compare OS between participants randomized to nivolumab + paclitaxel + ramucirumab compared to those randomized to paclitaxel + ramucirumab in the event that the trial is completed before the phase III portion.

III. To compare the overall response rate (ORR, including confirmed and unconfirmed, complete, and partial response, according to Response Evaluation Criteria in Solid Tumors \[RECIST 1.1\] criteria) between those randomized to nivolumab + paclitaxel + ramucirumab compared to those randomized to paclitaxel + ramucirumab among participants with measurable disease.

IV. To compare the overall disease control rate (DCR = ORR + stable disease) between those randomized to nivolumab + paclitaxel + ramucirumab compared to those randomized to paclitaxel + ramucirumab among participants with measurable disease.

V. To evaluate the safety and tolerability of each treatment regimen. VI. To compare health-related quality of life (QOL) by treatment arm at 8 weeks after randomization, measured using the Functional Assessment of Cancer Therapy - Gastric (FACT-Ga) Trial Outcome Index (TOI).

VII. To compare health-related QOL between treatment arms at 8 weeks after randomization using the FACT-Ga total score.

VIII. To compare longitudinal changes in health-related QOL between treatment arms using FACT-Ga TOI up to 24 weeks after randomization.

IX. To compare patient-reported symptoms using selected Patient-Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) items including gastrointestinal as well as constitutional symptoms of fatigue, anorexia, and weight loss between treatment arms.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 of each cycle, ramucirumab IV over 30-60 minutes on days 1 and 15 of each cycle, and paclitaxel IV over 30 minutes on days 1, 8 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan and magnetic resonance imaging (MRI) throughout the study. Patients may also optionally undergo blood sample collection on study.

ARM 2: Patients receive ramucirumab IV over 30-60 minutes on days 1 and 15 of each cycle and paclitaxel IV over 30 minutes on days 1, 8 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and MRI throughout the study. Patients may also optionally undergo blood sample collection on study.

After completion of study treatment, patients are followed up at 30, 60, 90 days and then every 6 months for up to 3 years.

Adding Nivolumab to Usual Treatment for People With Advanced Stomach or Esophageal Cancer, PARAMUNE Trial

Randomized Phase II/III Trial of 2nd Line Nivolumab + Paclitaxel + Ramucirumab Versus Paclitaxel + Ramucirumab in Patients With PD-L1 CPS &gt;/= 1 Advanced Gastric and Esophageal Adenocarcinoma (PARAMMUNE)

"NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."

The hazard ratio of DFS and the corresponding 95% confidence intervals will be estimated for subgroups defined by sex, race, and ethnicity, respectively.

The distribution of PFS will be estimated using the method of Kaplan-Meier and compared using a 1-sided stratified log-rank test.

The distribution of OS will be estimated using the method of Kaplan-Meier and compared using a 1-sided stratified log-rank test.

Will be compared across arms in participants with measurable disease via Fisher's exact test.

DCR = ORR + stable disease per Response Evaluation Criteria in Solid Tumors 1.1. Will be compared across arms in participants with measurable disease via Fisher's exact test.

National Cancer Institute (NCI)

Carcinoma, Squamous Cell

Neoplasms, Squamous Cell

Carboplatin

Patients receive OBP-301 by intratumoral injection on days -3, 12, and 26. Patients also receive carboplatin IV over 30 minutes and paclitaxel IV over 60 minutes on days 1, 8, 15, 22, and 29, and undergo radiation therapy on Monday through Friday beginning day 1 for 28 fractions over 5.5 weeks. All treatment continues in the absence of disease progression or unacceptable toxicity.

Radiation Therapy

Telomerase-specific Type 5 Adenovirus OBP-301

Terence M. Williams

Rutika Mehta

Eric D. Miller

Wayne L. Hofstetter

Geoffrey Y Ku

This phase I trial studies the side effects of OBP-301 when given together with carboplatin, paclitaxel, and radiation therapy in treating patients with esophageal or gastroesophageal cancer that invades local or regional structures. OBP-301 is a virus that has been designed to infect and destroy tumor cells (although there is a small risk that it can also infect normal cells). Chemotherapy drugs, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving OBP-301 with chemotherapy and radiation therapy may work better than standard chemotherapy and radiation therapy in treating patients with esophageal or gastroesophageal cancer.

PRIMARY OBJECTIVE:

I. To determine if the addition of OBP-301 to chemoradiation with carboplatin/paclitaxel is safe.

SECONDARY OBJECTIVES:

I. To assess toxicities associated with the addition of OBP-301 to chemoradiation.

II. To assess the number of clinical complete responses (cCR).

III. To assess the number of patients alive/without progression (progression-free survival \[PFS\]) and the number of patients alive (overall survival \[OS\]) at 1 and 2 years.

EXPLORATORY OBJECTIVE:

I. To report correlate outcomes - cCR, PFS and OS - with immune and virus-based correlative assays.

OUTLINE:

This study will evaluate an initial dose of OBP-301 and a de-escalated dose, if needed.

Patients receive OBP-301 by intratumoral injection via endoscopy on days -3, 12, and 26. Patients also receive carboplatin intravenously (IV) over 30 minutes and paclitaxel IV over 60 minutes on days 1, 8, 15, 22, and 29, and undergo radiation therapy on Monday through Friday beginning day 1 for 28 fractions over 5.5 weeks. All treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 and 6-8 weeks, then every 3 months for 2 years.

Testing the Addition of the Anti-cancer Viral Therapy Telomelysin™ to Chemoradiation for Patients With Advanced Esophageal Cancer and Are Not Candidates for Surgery

Phase I Trial With Expansion Cohort of OBP-301 (Telomelysin™) and Definitive Chemoradiation for Patients With Locally Advanced Esophageal and Gastroesophageal Cancer Who Are Not Candidates for Surgery

All adverse events will be graded according to Common Terminology Criteria for Adverse Events version 5.0

Assessed using Common Terminology Criteria for Adverse Events version 5.0. Counts of all adverse events (AEs) by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm and within the subset of AEs related to treatment. No formal statistical testing will be performed on these summary data.

If one of the OBP-301 regimens is declared to be safe, the number of cCRs will be reported. No formal statistical testing will be performed on these summary data.

If one of the OBP-301 regimens is declared to be safe, number of patients alive without progression will be reported. No formal statistical testing will be performed on these summary data.

If one of the OBP-301 regimens is declared to be safe, number of patients alive will be reported. No formal statistical testing will be performed on these summary data.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Adding Nivolumab to Usual Treatment for People With Advanced Stomach or Esophageal Cancer, PARAMUNE Trial	NCT06203600	Advanced Esopha... Advanced Gastri... Advanced Gastro... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Metastatic Esop... Metastatic Gast... Metastatic Gast... Unresectable Es... Unresectable Ga... Unresectable Ga...	Biospecimen Col... Computed Tomogr... Magnetic Resona... Nivolumab Paclitaxel Questionnaire A... Ramucirumab	18 Years -	National Cancer Institute (NCI)
Testing the Addition of the Anti-cancer Viral Therapy Telomelysin™ to Chemoradiation for Patients With Advanced Esophageal Cancer and Are Not Candidates for Surgery	NCT04391049	Advanced Esopha... Advanced Gastro... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Unresectable Ga... Squamous Cell C... Squamous Cell C...	Carboplatin Paclitaxel Radiation Thera... Telomerase-spec...	18 Years -	NRG Oncology
Testing the Addition of the Anti-cancer Viral Therapy Telomelysin™ to Chemoradiation for Patients With Advanced Esophageal Cancer and Are Not Candidates for Surgery	NCT04391049	Advanced Esopha... Advanced Gastro... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Unresectable Ga... Squamous Cell C... Squamous Cell C...	Carboplatin Paclitaxel Radiation Thera... Telomerase-spec...	18 Years -	NRG Oncology

Spots Global Cancer Trial Database for advanced esophageal adenocarcinoma