Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Stomach Neoplasms

Esophageal 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

Stomach Cancer

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

Jaffer A Ajani

This early phase I trial studies how well pembrolizumab works in treating patients with gastroesophageal adenocarcinoma that has spread to other places or cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVES:

I. To estimate the overall response rate (ORR) of intravenous administration of pembrolizumab by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in adult subjects with advanced (unresectable and/or metastatic) and previously treated gastroesophageal adenocarcinoma.

SECONDARY OBJECTIVES:

I. To evaluate the duration of response (DOR), disease control rate (DCR), time to progression (TTP), progression-free survival (PFS), and overall survival (OS) using RECIST 1.1 and immune-related (ir)RECIST criteria.

II. To perform exploratory biomarkers to study the correlation between immunological and molecular changes in tumor tissues and peripheral blood with clinical outcomes (DOR, DCR, TTP, PFS, and OS) using RECIST 1.1, and irRECIST rate of adverse events.

III. To determine the safety and tolerability of intravenous administration of pembrolizumab or pembrolizumab plus ramucirumab in adult subjects with advanced (unresectable and/or metastatic) and previously treated gastroesophageal adenocarcinoma.

EXPLORATORY OBJECTIVES:

I. To explore the association between PD-L1 expression by immunohistochemistry, shed PD-L1 levels, somatic gene expression profiling and antitumor efficacy of pembrolizumab based on RECIST 1.1 imaging criteria as well as overall survival.

II. To explore the relationship between genomic variation and response to the treatment administered.

III. Tissue and blood immune monitoring will be conducted through our immune platform group as detailed per the biomarker section based on 3 biopsies done at the following time points: 1) pre-treatment, 2) 6 weeks after therapy, and 3) and an optional biopsy upon progression.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 12 weeks thereafter.

Pembrolizumab in Treating Patients With Metastatic or Unresectable Gastroesophageal Adenocarcinoma

A Pilot Study of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastroesophageal Adenocarcinoma

Defined as the proportion of the subjects in the analysis population who have a complete response (CR) or partial response (PR). Responses are based on assessments by the blinded MD Anderson radiology per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Exact method based on binomial distribution (Clopper-Pearson method).

Based on assessments by MD Anderson radiology per RECIST 1.1. Summary statistics using Kaplan-Meier method, if sample size permits.

Defined as the percentage of subjects who have achieved CR, PR, or stable disease (SD) for at least 24 weeks based on assessments by MD Anderson radiology per RECIST 1.1. Exact method based on binomial distribution (Clopper-Pearson method).

Assessed per RECIST 1.1 based on assessments by MD Anderson radiology. Summary statistics using Kaplan-Meier method.

Summary statistics using Kaplan-Meier method.

Defined by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Adverse events will be assessed. Specific events will be collected and designated as events of clinical interest (ECIs).

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Lenvatinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receive pembrolizumab IV over 30 minutes on day 1 and lenvatinib PO QD, Treatment repeats every 42 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity.

Mariela Blum, MD

Mariela Blum

This early phase I trial studies the effect of pembrolizumab and lenvatinib in treating patients with gastroesophageal adenocarcinoma that has spread to other places in the body (advanced/metastatic) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and lenvatinib may kill more tumor cells.

PRIMARY OBJECTIVE:

I. To estimate the overall response rate (ORR) of pembrolizumab plus lenvatinib by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in adult subjects with previously treated advanced (unresectable and/or metastatic) gastroesophageal adenocarcinoma.

SECONDARY OBJECTIVES:

I. To evaluate the duration of response (DOR), disease control rate (DCR), time-to-progression (TTP), progression-free survival (PFS), using RECIST 1.1 and immune-related (i)RECIST criteria and overall survival (OS).

II. To determine the safety and tolerability of pembrolizumab plus lenvatinib in adult subjects with previously treated advanced (unresectable and/or metastatic) gastroesophageal adenocarcinoma.

EXPPLORATORY OBJECTIVES:

I. To perform exploratory biomarker analyses to study the correlation between immunological and molecular changes in tumor tissues and peripheral blood with clinical outcomes (DOR, DCR, TTP, PFS, and OS) using RESIST 1.1 and iRECIST.

II. To explore the association between PD-L1 expression by immunohistochemistry (IHC), shed PD-L1 levels, somatic gene expression profiling (18-gene T-cell inflamed GEP) and antitumor efficacy of pembrolizumab based on RECIST 1.1 imaging criteria as well as OS.

III. To explore the relationship between genomic variation and response to the treatment administered.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and lenvatinib orally (PO) once daily (QD). Treatment repeats every 42 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.

Pembrolizumab and Lenvatinib for the Treatment of Advanced, Unresectable, or Metastatic Gastroesophageal Adenocarcinoma

A Pilot Study of Pembrolizumab and Lenvatinib Combination Therapy in Patients With Previously Treated Advanced Gastroesophageal Adenocarcinoma

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Paclitaxel

Albumin-Bound Paclitaxel

Trifluridine

Immunoglobulins

Ramucirumab

Lexatumumab

Immunoglobulins, Intravenous

Tubulin Modulators

Antimitotic Agents

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Antiviral Agents

Patients receive TAS-102 PO BID on days 1-5 and 8-12, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

Patients receive paclitaxel IV over 1-96 hours on days 1, 8, and 15, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

Quality-of-Life Assessment

Trifluridine and Tipiracil Hydrochloride

Darryl A. Outlaw

ACCRU Operations

Mohamad B. Sonbol

Syma Iqbal

Jason S. Starr

Arun Nagarajan

Pashtoon M. Kasi

Clinical Trial Information Program

Michael Gibson

Anthony J. Jaslowski

Mohamad B Sonbol

This phase II trial studies the effect of the combination of ramucirumab and trifluridine/tipiracil or paclitaxel in treating patients with previously treated gastric or gastroesophageal junction cancer that has spread to other places in the body (advanced). Ramucirumab may damage tumor cells by targeting new blood vessel formation. Trifluridine/tipiracil is a chemotherapy pill and that may damage tumor cells by damaging their deoxyribonucleic acid (DNA). Paclitaxel may block cell growth by stopping cell division which may kill tumor cells. Giving ramucirumab and trifluridine/tipiracil will not be worse than ramucirumab and paclitaxel in treating gastric or gastroesophageal junction cancer.

PRIMARY OBJECTIVE:

I. To compare, in a non-inferiority fashion, the progression-free survival (PFS) in patients with metastatic refractory gastric/gastroesophageal junction (GEJ) adenocarcinoma receiving the combination of ramucirumab with trifluridine and tipiracil hydrochloride (TAS-102) versus (vs.) paclitaxel and ramucirumab.

SECONDARY OBJECTIVES:

I. To assess overall survival (OS) in this patient population for each regimen. II. Assess changes in patient quality of life (QOL) as measured by the linear analogue self-assessment (LASA) questionnaire for each regimen.

III. To determine the safety of the combination of ramucirumab with TAS-102 in this patient population.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive TAS-102 orally (PO) twice daily (BID) on days 1-5 and 8-12, and ramucirumab intravenously (IV) over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive paclitaxel IV over 1-96 hours on days 1, 8, and 15, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30-35 days, then every 3 months for up to 3 years.

Ramucirumab and Trifluridine/Tipiracil or Paclitaxel for the Treatment of Patients With Previously Treated Advanced Gastric or Gastroesophageal Junction Cancer

Ramucirumab Plus Trifluridine/Tipiracil (TAS-102) for Patients With Previously Treated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: An Investigator-Initiated, Randomized Non-Inferiority Phase 2 Study

Progression free survival is defined as the time interval between randomization date and the date of disease progression or death (referred to as an "event"), whichever occurs first. Disease progression will be determined based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. The median progression free survival will be estimated using the Kaplan-Meier method for each arm, corresponding 95% confidence intervals, and hazard ratio comparing the treatment arm to the control arm will be reported.

Median OS will be estimated using the Kaplan-Meier method. Patients who do not experience death while on study will be censored at the last known date alive. The median OS and corresponding 95% confidence interval will be reported by arm.

Patient reported QOL outcomes will be collected using the Linear Analog Self-Assessment (LASA) Questionnaire. Data will be collected each cycle. Mean values of the first question (regarding overall QOL) at each cycle will be plotted, and stratified by arm.

Adverse events will be recorded using Common Terminology Criteria for Adverse Events version 5.0. The proportion of patients who experience a grade 3+ adverse event at least possibly related to treatment will be reported by arm.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pembrolizumab in Treating Patients With Metastatic or Unresectable Gastroesophageal Adenocarcinoma	NCT03395847	Advanced Gastro... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Gastroesophagea... Metastatic Gast... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Postneoadjuvant... Postneoadjuvant... Unresectable Ga...	Pembrolizumab	18 Years -	M.D. Anderson Cancer Center
Pembrolizumab and Lenvatinib for the Treatment of Advanced, Unresectable, or Metastatic Gastroesophageal Adenocarcinoma	NCT05041153	Advanced Gastri... Advanced Gastro... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Metastatic Gast... Metastatic Gast... 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... Unresectable Ga...	Lenvatinib Pembrolizumab	18 Years -	M.D. Anderson Cancer Center
Ramucirumab and Trifluridine/Tipiracil or Paclitaxel for the Treatment of Patients With Previously Treated Advanced Gastric or Gastroesophageal Junction Cancer	NCT04660760	Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Locally Advance... Locally Advance... Metastatic Gast... Metastatic Gast... 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...	Paclitaxel Quality-of-Life... Ramucirumab Trifluridine an...	18 Years -	Academic and Community Cancer Research United

Spots Global Cancer Trial Database for postneoadjuvant therapy stage iii gastric cancer ajcc v8