Neoplasms

Digestive System Diseases

All Conditions

Gland and Hormone Related Diseases

Rare Diseases

Behaviors and Mental Disorders

Esophageal Neoplasms

Carcinoma

Pancreatic Neoplasms

Stomach Neoplasms

Carcinoma, Ductal

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Head and Neck Neoplasms

Esophageal Diseases

Stomach Diseases

Esophageal Cancer

Pancreatic Cancer

Quality of Life

Bile Duct Cancer

Stomach Cancer

Intrahepatic Cholangiocarcinoma

Dermatologic Agents

All Drugs and Chemicals

Micronutrients

Zinc Sulfate

Zinc

Trace Elements

Astringents

Patients receive zinc PO TID for months 1 and 2 only of the first 4 months on therapy.

Patients receive zinc PO TID for months 3 and 4 only of the first 4 months on therapy.

Olatunji B. Alese, MD

This randomized study examines how well zinc works in improving quality of life in patients with gastrointestinal cancer that cannot be removed by surgery who are receiving chemotherapy. Zinc may help to improve patient's quality of life by preventing zinc deficiency.

PRIMARY OBJECTIVE:

I. Assess the effects on quality of life (QOL) when supplementing zinc in upper gastrointestinal (GI) cancer patients while they are receiving chemotherapy.

SECONDARY OBJECTIVES:

I. Correlate hypoalbuminemia with serum zinc deficiency.

II. Correlate zinc deficiency with neutropenia.

OUTLINE: Patients are randomized into 1 of 2 groups.

GROUP I: Patients receive zinc orally (PO) thrice daily (TID) for months 1 and 2 only of the first 4 months on therapy.

GROUP II: Patients receive zinc orally (PO) TID for months 3 and 4 only of the first 4 months on therapy.

Effects on Quality of Life With Zinc Supplementation in Patients With Gastrointestinal Cancer

Effects on QOL When Zinc is Supplemented in Patients With Upper GI Cancer on Chemotherapy

Plan may be reevaluated at the time of publication.

Quality of life (QOL) will be evaluated through patient subjective responses to the QOL survey.

Zinc levels will be monitored monthly with blood tests. Low zinc will be defined as under 60 mcg.

Albumin levels will be monitored monthly with blood tests. Low albumin will be defined as under 3.5 gm/dl.

National Cancer Institute (NCI)

National Institutes of Health (NIH)

Emory University

Principal Investigator

Symptoms and General Pathology

Recurrence

Adenocarcinoma

Disease Attributes

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Olaparib

Immunoglobulins

Ramucirumab

Lexatumumab

Poly(ADP-ribose) Polymerase Inhibitors

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunologic Factors

Enzyme Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive olaparib PO BID on days 1-14 of each cycle and ramucirumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Michael Cecchini

This phase I/II trial studies the side effects and best dose of olaparib when given together with ramucirumab and how well they work in treating patients with gastric or gastroesophageal junction cancer that has spread to other places in the body (metastatic), has come back (recurrent), or cannot be removed by surgery (unresectable). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as ramucirumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving olaparib and ramucirumab may work better in treating patients with gastric or gastroesophageal junction cancer compared to ramucirumab and paclitaxel (a chemotherapy drug) or ramucirumab alone.

PRIMARY OBJECTIVES:

I. To determine the safe dose of olaparib with ramucirumab, but not to exceed olaparib dose of 300 mg twice daily (tablet formulation). (Phase I) II. To determine the efficacy of olaparib plus ramucirumab as measured by the objective response rates (ORR) stratified by BROCA-HR biomarker status. (Phase II).

SECONDARY OBJECTIVES:

I. To estimate median progression-free survival (PFS) stratified by BROCA-HR biomarker status.

II. To estimate median overall survival (OS) stratified by BROCA-HR biomarker status.

III. To measure the prevalence of the BROCA-HR biomarker in our study population.

IV. To determine toxicity of olaparib and ramucirumab combination.

EXPLORATORY OBJECTIVES:

I. To assess the correlation between the signature 3 status, and mutations in BROCA-HR panel.

II. To evaluate the association between findings from BROCA-HR panel with response to therapy.

III. To evaluate the association between findings from BROCA-HR panel and signature 3 results with response to therapy.

IV. To determine results of immunoassay for poly-ADP-ribosylated (PAR) substrates in tumor tissue.

V. To create a PDX model to study deoxyribonucleic acid (DNA) repair in gastric tumors treated with PARP inhibitors (PARPi) from both pre-treatment biopsy and repeat biopsy after 16 weeks of treatment.

VI. Development of a novel genomic assay for BRCAness. VII. Defining T cell receptor diversity of gastric cancer patients +/- BRCAness.

VIII. Biobank additional tumor tissue for future genomic analysis. IX. Biobank peripheral blood for future genomic analysis and assessment of circulating tumor DNA.

OUTLINE: This is a phase I, dose-escalation study of olaparib followed by a phase II study.

Patients receive olaparib orally (PO) twice daily (BID) on days 1-14 of each cycle and ramucirumab intravenously (IV) over 60 minutes on day 1 of each cycle. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and then every 6 weeks thereafter.

Olaparib and Ramucirumab in Treating Patients With Metastatic or Locally Recurrent Gastric or Gastroesophageal Junction Cancer That Cannot Be Removed by Surgery

A Phase 1/2 Study of Olaparib in Combination With Ramucirumab in Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma (10017760)

The association of BROCA HR assay with Signature 3 will be assessed using a series of contingency table analyses. The association of the presence of an individual mutation from the BROCA HR panel with the signature 3 (yes/no) using Fisher's exact test. Using a Cochran Mantel Haenzel test the relationship across all three measures will be examined. Finally, the relationship of each of these measures with response will be examined. To do this multiple logistic regression models can be fit with the response (complete response/partial response vs stable disease/partial disease) considered as the outcome variable and the assay measures can be used predictors.

Will be assessed by National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) for Adverse Events version 5.0.

Will be defined as complete or partial response assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Will be estimated using the 95% confidence interval (CI) based on Wilson's method. A 5% 2-sided alpha will be used. The Wilcoxon rank sum test and Fisher's exact test will be applied to study the association between the response status and the continuous and categorical variables, respectively. The generalized non-linear model and logistic regression will be applied for multivariable data analysis. The adjusted p-value and 95% CI of the odds ratio will be reported.

Will be compared for duration of response survival with Kaplan-Meier estimates and log-rank tests. The Rothman CI will be reported. In addition, the possible risk factors will be compared for survival with log-rank test. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age and stage of disease of the PFS data. The adjusted p-values of the hazard ratios and the adjusted 95% confidence interval will be reported.

Will be compared for duration of response survival with Kaplan-Meier estimates and log-rank tests. The Rothman CI will be reported. In addition, the possible risk factors will be compared for survival with log-rank test. The adjusted p-values of the hazard ratios and the adjusted 95% confidence interval will be reported.

Will be assessed by NCI CTCAE version 5.0. Will be tabulated by type and grade and compared to established rates for ramucirumab monotherapy. Ninety-five percent confidence intervals will be calculated for each of these.

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Neoplasms, Second Primary

Neoplasms, Squamous Cell

Adavosertib

Patients undergo radiation therapy QD 5 days per week for 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive adavosertib PO QD for 2-5 days (depending on dose level) during weeks 1 and 3 of radiation therapy in the absence of disease progression or unacceptable toxicity.

Radiation Therapy

Eric D Miller

This phase I trial investigates the side effects and best dose of adavosertib and how well it works when given in combination with radiation therapy in treating patients with esophageal or gastroesophageal junction cancer for which no treatment is currently available (incurable). Adavosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving adavosertib together with radiation therapy kill more tumor cells than radiation therapy alone in treating patients with esophageal and gastroesophageal junction cancer.

PRIMARY OBJECTIVE:

I. To identify the maximally tolerated dose of adavosertib (AZD1775) to be used in combination with radiation therapy for patients with esophageal/gastroesophageal junction (GEJ) cancer that is metastatic or inoperable and not eligible for definitive chemoradiation.

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity. II. To evaluate the efficacy of AZD1775 when administered in combination with radiation therapy by assessing changes in Ogilvie dysphagia score following treatment, time to second intervention for dysphagia, and overall survival.

III. To identify biomarkers that are predictive for response to experimental therapy.

OUTLINE: This is a dose escalation study of adavosertib.

Patients undergo radiation therapy once daily (QD) 5 days per week for 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive adavosertib orally (PO) QD for 2-5 days (depending on dose level) during weeks 1 and 3 of radiation therapy in the absence of disease progression or unacceptable toxicity.

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

Testing the Addition of an Anti-cancer Drug, Adavosertib, to Radiation Therapy for Patients With Incurable Esophageal and Gastroesophageal Junction Cancers

A Phase 1 Trial Combining WEE1 Inhibitor Adavosertib (AZD1775) With Radiation Therapy for Metastatic or Inoperable and Ineligible for Definitive Chemoradiation Esophageal and Gastroesophageal Junction Cancer

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.

Will employ a BOIN design where the target toxicity rate for the MTD is 25% with 75% dose-elimination cut-off.

Frequency and severity of adverse events and tolerability of the regimen will be collected and summarized with descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

Will be calculated with 95% binomial confidence intervals.

Patient dysphagia will be evaluated using the Ogilvie dysphagia score, comparing pre-treatment to post-treatment scores

Survival will initially be analyzed using Kaplan-Meier methods, resulting in median survival times with 95% confidence interval (CI).

The scores will be summarized and compared using paired t-test or Wilcoxon signed-rank test. Patient dysphagia will be evaluated using the Ogilvie dysphagia score, comparing pre-treatment to post-treatment scores.

Will be described graphically or summary measures (e.g. mean and standard errors, or median and range) and compared between responders and non-responders using a two sample t-test or Wilcoxon test if the data is not normally distributed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effects on Quality of Life With Zinc Supplementation in Patients With Gastrointestinal Cancer	NCT03819088	Gastric Carcino... Liver and Intra... Unresectable Es... Unresectable Pa...	Zinc	-	Emory University
Olaparib and Ramucirumab in Treating Patients With Metastatic or Locally Recurrent Gastric or Gastroesophageal Junction Cancer That Cannot Be Removed by Surgery	NCT03008278	Metastatic Esop... Metastatic Gast... Metastatic Gast... Recurrent Esoph... Recurrent Gastr... Recurrent Gastr... Stage III Esoph... Stage III Gastr... Stage IV Esopha... Stage IV Gastri... Unresectable Es... Unresectable Ga... Unresectable Ga...	Olaparib Ramucirumab	18 Years -	National Cancer Institute (NCI)
Testing the Addition of an Anti-cancer Drug, Adavosertib, to Radiation Therapy for Patients With Incurable Esophageal and Gastroesophageal Junction Cancers	NCT04460937	Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Distal Esophagu... Gastric Cardia ... Metastatic Esop... Metastatic Esop... Metastatic Gast... Metastatic Mali... Metastatic Mali... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... 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... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Unresectable Es... Unresectable Es... Unresectable Es... Unresectable Ga...	Adavosertib Radiation Thera...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for unresectable esophageal carcinoma