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

Head and Neck Neoplasms

Esophageal Diseases

Stomach Cancer

Esophageal Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Irinotecan

Immunoglobulins

Ramucirumab

Topoisomerase I Inhibitors

Enzyme Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive ramucirumab IV over 30 minutes and MM-398 IV over 90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Liposomal Irinotecan

Quality-of-Life Assessment

Questionnaire Administration

Afsaneh Barzi, MD

This phase I/II trial studies the side effects and best dose of MM-398 and ramucirumab in treating patients with gastric cancer or gastroesophageal junction adenocarcinoma. MM-398 contains a chemotherapy drug called irinotecan, which in its active form interrupts cell reproduction. MM-398 builds irinotecan into a container called a liposome which may be able to release the medicine slowly over time to reduce side effects and increase its ability to kill tumor cells. 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 MM-398 and ramucirumab together may work better in treating patients with gastric cancer or gastroesophageal junction adenocarcinoma.

PRIMARY OBJECTIVES:

I. Phase I portion is to determine the recommended phase II dose (RP2D) of liposomal irinotecan (MM-398) when given in combination with ramucirumab at 8 mg/kg every 2 weeks in patients with gastric and gastroesophageal adenocarcinoma (GEAC) who had failed or are intolerant of platinum-based therapy.

II. Phase II portion is to assess the preliminary efficacy and tolerability of MM-398 in combination with ramucirumab in patients with GEAC who had failed or are intolerant of platinum based therapy.

SECONDARY OBJECTIVES:

I. To estimate the best overall response rate through up to three cycles of therapy among patients with measurable disease at study entry.

II. To assess the incidence and severity of toxicity of the combination.

EXPLORATORY OBJECTIVES:

I. Descriptive of quality of life domains using Patient-Reported Outcomes Measurement Information System (PROMIS) global health instrument (PRO).

II. Descriptive of altered genes on liquid biopsies. III. To assess the effect of the anti-angiogenic ramucirumab on distribution of MM-398 via magnetic resonance imaging (MRI) with and without ferumoxytol.

OUTLINE: This is a phase I, dose escalation study of MM-398followed by a phase II study.

Patients receive ramucirumab intravenously (IV) over 30 minutes and MM-398 IV over 90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 6 months.

MM-398 and Ramucirumab in Treating Patients With Gastric Cancer or Gastroesophageal Junction Adenocarcinoma

Phase I/II Study of MM-398 in Combination With Ramucirumab After Platinum Failure in Gastric Cancer

DLT is defined as follows: For hematological toxicity: Drug-related grade 4 neutropenia for more than 5 days without fever or infection; Grade 4 neutropenia of any duration accompanied by fever or infection, Grade 4 thrombocytopenia. For non-hematological toxicity: All grade 3-4 that represents a 2 grade increase over baseline, excluding: Untreated or inadequately treated nausea, vomiting, diarrhea lasting shorter than 24 hours; Alopecia; Grade 3 fatigue that returns to grade 2 or less within 7 days; Grade 3 laboratory abnormalities that are not considered clinically significant and that return to grade 2 or less within 72 hours.

PFS will be calculated from treatment start date to date of disease progression or date of death due to any cause, or to the time of last follow-up, whichever occurs first.

BOR will be evaluated from start of treatment until progression/recurrence.

Analyses of safety/toxicity will be performed for all patients having received at least one dose of study drug.

National Cancer Institute (NCI)

Ipsen

University of Southern California

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
MM-398 and Ramucirumab in Treating Patients With Gastric Cancer or Gastroesophageal Junction Adenocarcinoma	NCT03739801	Locally Advance... Metastatic Gast... Metastatic Unre... Unresectable Ga... Gastric Adenoca... Gastroesophagea...	Liposomal Irino... Quality-of-Life... Questionnaire A... Ramucirumab	18 Years -	University of Southern California
MM-398 and Ramucirumab in Treating Patients With Gastric Cancer or Gastroesophageal Junction Adenocarcinoma	NCT03739801	Locally Advance... Metastatic Gast... Metastatic Unre... Unresectable Ga... Gastric Adenoca... Gastroesophagea...	Liposomal Irino... Quality-of-Life... Questionnaire A... Ramucirumab	18 Years -	University of Southern California

Spots Global Cancer Trial Database for metastatic unresectable gastric adenocarcinoma