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

NCT03739801 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: 3G-18-1NCI-2018-02028P30CA014089
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Locally Advanced Unresectable Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Metastatic Unresectable Gastric Adenocarcinoma; Unresectable Gastroesophageal Junction Adenocarcinoma; Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT) (Phase I)

  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.

  Up to 28 days

• Progression-free survival (PFS) (Phase II)

  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.

  Up to 6 months

Secondary Outcomes (2)

• Best overall response (BOR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria

  Up to 6 months

• Incidence of adverse events graded according to CTCAE version 4.0

  Up to 6 months

Study Arms (1)

Treatment (ramucirumab, liposomal irinotecan[MM-398])

EXPERIMENTAL

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.

Drug: Liposomal Irinotecan; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Biological: Ramucirumab

Interventions

Liposomal Irinotecan DRUG

Given IV

Also known as: Irinotecan Liposome, MM-398, nal-IRI, Nanoliposomal Irinotecan, Nanoparticle Liposome Formulation of Irinotecan, Onivyde, PEP02

Treatment (ramucirumab, liposomal irinotecan[MM-398])

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (ramucirumab, liposomal irinotecan[MM-398])

Questionnaire Administration OTHER

Ancillary studies

Treatment (ramucirumab, liposomal irinotecan[MM-398])

Ramucirumab BIOLOGICAL

Given IV

Also known as: anti-VEGFR-2 fully human monoclonal antibody IMC-1121B, Cyramza, IMC-1121B, LY3009806

Treatment (ramucirumab, liposomal irinotecan[MM-398])

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient has a histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma
• The patient has metastatic disease or locally advanced and unresectable disease that is evaluable, by radiological imaging per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). (MRI candidates must have measurable disease in liver.
• The patient has documented disease progression or intolerance of chemotherapy during first-line platinum-based chemotherapy for metastatic disease, or during or within 6 months after the last dose of neoadjuvant or adjuvant therapy
• Additional lines of therapy are permitted as long as patient had received a platinum and/or a fluoropyrimidine component. Exposure to antiangiogenic agent (either approved or experimental treatment) is permitted. Exposure to antineoplastic therapy in addition to platinums and/or fluoropyrimidines is acceptable if the agents were used in the first-line metastatic or neoadjuvant/adjuvant setting
• The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count \>= 1,000/microliter (mcL)
• Platelets \>= 75,000/mcL
• Total bilirubin \< 1.5 x institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SPGT\]) =\< 2.5 x institutional upper limit of normal for patients without liver metastasis and =\< 5 x institutional upper limit of normal for patients without liver metastasis
• Creatinine \< 1.5 x institutional upper limit of normal
• International normalized ratio (INR) \< 1.5 x ULN and partial thromboplastin time \< 5 seconds above upper liming of normal (ULN), unless the patient is receiving anticoagulation therapy. Patients on full-dose anticoagulation therapy must be on a stable dose of oral anticoagulation therapy or low molecular weight heparin for a minimum of 14 days. Patients receiving warfarin must have an INR \< 3.0 x ULN and have no bleeding within 14 days prior to the first dose of ramucirumab or pathological condition that carries a high risk of bleeding, such as tumors involving major vessels or known varices
• The patient has provided written informed consent prior to any study-specific procedures and is amenable to compliance with protocol schedules and testing
• The patient has an estimated life expectancy of \> 12 weeks in the judgment of the investigator
• The patient has resolution to grade 1 by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (National Cancer Institute \[NCI\] 2009), of all clinically significant toxic effects of previous anticancer therapy. Stable grade 2 neuropathy is permitted. Patients with nonserious and non-life threatening toxicities, such as alopecia, altered taste, or nail changes, can be considered
• The patient, if male, is sterile (including vasectomy confirmed by post-vasectomy semen analysis) or agrees to use a reliable method of birth control and to not donate sperm during the study and for at least 12 weeks following the last dose of study treatment

You may not qualify if:

• The patient has squamous cell or undifferentiated gastric cancer
• The patient received systemic therapy within 28 days prior to enrollment
• The patient received radiotherapy within 14 days prior to enrollment. Palliative radiotherapy during the study, if clinically indicated, can be considered after consultation with the principal investigator (PI). Any lesion requiring palliative radiotherapy or which has been previously irradiated cannot be considered for response assessment
• The patient has documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression. Screening of asymptomatic patients is not required.
• The patient has a significant bleeding disorder or vasculitis or had a grade \>= 3 bleeding episode within 12 weeks prior to enrollment
• The patient experienced any arterial thromboembolic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to enrollment.
• The patient has symptomatic congestive heart failure (CHF; New York Heart Association IIIV) or symptomatic or poorly controlled cardiac arrhythmia
• The patient has uncontrolled hypertension, as defined in CTCAE version 4.0, prior to initiating study treatment, despite antihypertensive intervention. CTCAE Version 4.0 defines uncontrolled hypertension as grade \> 2 hypertension; clinically, the patient continues to experience elevated blood pressure (systolic \> 160 mmHg and/or diastolic \> 100 mmHg) despite medications)
• The patient underwent major surgery within 28 days prior to initiation or central venous access device placement within 7 days prior to enrollment
• The patient plans to undergo elective major surgery during the course of the trial
• The patient has a history of gastrointestinal (GI) perforation or fistula within 6 months prior to enrollment
• The patient has a history of inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) \< 12 months prior to enrollment
• The patient has an acute or subacute bowel obstruction or history of chronic diarrhea that is considered clinically significant in the opinion of the investigator
• The patient has either of the following:
• Cirrhosis at a level of Child-Pugh B (or worse)

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator
• Ipsen: collaborator

Study Sites (1)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Interventions

irinotecan sucrosofate; Ramucirumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Afsaneh Barzi, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2018
• First Posted: November 14, 2018
• Study Start: April 6, 2020
• Primary Completion: April 6, 2022
• Study Completion: April 6, 2023
• Last Updated: March 27, 2020

Record last verified: 2020-03

Locations

US (1)