Phase I/II Trial of Tivantinib With FOLFOX for the Treatment of Advanced Solid Tumors and Previously Untreated Metastatic Adenocarcinoma of the Distal Esophagus, Gastroesophageal Junction or Stomach

NCT ID: NCT01611857

Last Updated: 2016-11-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2015-08-31

Brief Summary

This study is a Phase I/II trial of Tivantinib plus FOLFOX for the treatment of patients with advanced solid tumors. In Phase I the Maximum Tolerated Dose (MTD) will be determined; in Phase II patients with first-line metastatic GE cancer will be treated at the MTD. It is hypothesized that the response rate (RR) will be improved from 45% to at least 65% under this regimen.

Detailed Description

This is a Phase I, open-label, non-randomized, dose-escalation study with a Phase II portion planned upon reaching the Maximum Tolerated Dose or recommended Phase II dose (RP2D). Phase I: The first cycle of the Phase I portion of the trial will be considered the Dose Limiting Toxicity evaluation period. Patients with advanced solid tumors will be treated with Tivantinib on Days 1 to 14 and with FOLFOX on Day 1. Following evaluation of the Dose Limiting Toxicities, doses will be escalated/reduced according to the protocol with 3 to 6 patients treated per dose level until the Maximum Tolerated Dose is determined.

Conditions

Malignant Solid Tumour; Gastroesophageal Cancer

Keywords

Advanced solid tumors; First-Line Metastatic GE cancer; c-Met Inhibitor; Tivantinib; FOLFOX

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Maximum Tolerated Dose

Phase I trial of Tivantinib plus FOLFOX for the treatment of patients with advanced solid tumors followed by a Phase II portion for patients with first-line metastatic GE cancer.

Group Type: EXPERIMENTAL

Tivantinib

Intervention Type: DRUG

Patients with advanced solid tumors will be treated with oral Tivantinib (120, 240, or 360 mg BID) daily for 14 days in cycles of 14 days.

FOLFOX

Intervention Type: DRUG

The FOLFOX treatment regimen is started on Day 1 of each cycle and consists of 5-Fluorouracil (5-FU) 400 mg/m\^2, 5-FU continuous IV 2400 mg/m\^2 over 46 hours, leucovorin 400 mg/m\^2 IV, and oxaliplatin 85 mg/m\^2.

Interventions

Tivantinib

Patients with advanced solid tumors will be treated with oral Tivantinib (120, 240, or 360 mg BID) daily for 14 days in cycles of 14 days.

Intervention Type: DRUG

FOLFOX

The FOLFOX treatment regimen is started on Day 1 of each cycle and consists of 5-Fluorouracil (5-FU) 400 mg/m\^2, 5-FU continuous IV 2400 mg/m\^2 over 46 hours, leucovorin 400 mg/m\^2 IV, and oxaliplatin 85 mg/m\^2.

Intervention Type: DRUG

Other Intervention Names

ARQ 197; 5-FU; Leucovorin; Oxaliplatin; Levoleucovorin; 5-Fluorouracil

Eligibility Criteria

Inclusion Criteria

• Life expectancy ≥12 weeks.
• Karnofsky performance status ≥70%
• Patients must have measurable disease per RECIST Version 1.1.
• Adequate hematologic function defined as:
• Absolute neutrophil count (ANC) ≥1500/μL
• Hemoglobin (Hgb) ≥9 g/dL (5.6 mmol/L)
• Platelets ≥100,000/uL
• Adequate liver function defined as:
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST <2.5 x the institutional upper limit of normal (ULN) or ≤5.0 x the institutional ULN in patients with liver metastases.
• Total bilirubin within normal limits (WNL) (or ≤1.5 x the institutional ULN in patients with liver metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin within normal limits in patients with well documented Gilbert Syndrome).
• Serum creatinine <1.5 X ULN or calculated 24-hour creatinine clearance >40 mL/min.
• Patients who are on coumadin should have an international normalized ratio (INR) value within the therapeutic range (i.e., 2 to 3 x ULN). Patients who are on stable, chronic doses of coumadin are eligible.

PHASE I ONLY

•Patients must have histologically confirmed solid tumor malignancy that is metastatic or unresectable and for which standard therapy would include FOLFOX or for which standard curative or palliative measures do not exist or are no longer effective.

PHASE II ONLY

• Histologic documentation of adenocarcinoma of the esophagus, GE junction, or stomach.
• Metastatic GE cancer as documented by radiologic study or surgical evidence of metastatic disease.
• No prior chemotherapy for metastatic disease. Previous combined modality therapy for locally advanced disease is allowed if completed ≥6 months prior to recurrence (acceptable chemotherapy drugs include 5-FU, capecitabine, cisplatin, carboplatin, paclitaxel, oxaliplatin, and docetaxel).
• Prior radiation therapy is allowed. At least 4 weeks must have elapsed from completion of the radiation therapy and all signs of toxicity must have resolved.
• Prior adjuvant chemotherapy is allowed if completed ≥6 months prior to the documentation of metastatic disease.

Exclusion Criteria

• Patients with known central nervous system (CNS) metastases may be enrolled, provided the metastases have undergone treatment, the patient is asymptomatic, and the patient does not require antiepileptic drugs or steroids as treatment for the CNS metastases.
• Patients with poorly controlled or clinically significant atherosclerotic vascular disease including New York Heart Association Grade 3 or greater congestive heart failure; unstable angina ; myocardial infarction, cardiovascular accident, transient ischemic accidents, angioplasty, cardiac or vascular stenting in the past 6 months; or ventricular arrhythmia requiring medication. Patients with previously diagnosed symptomatic bradycardia will be ineligible.
• Medical history of prolonged QT syndrome (>450 ms).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit safety or compliance with study requirements.
• History of hypersensitivity to active or inactive excipients of any component of treatment (5-FU, leucovorin, oxaliplatin, or Tivantinib), or known dipyrimidine dehydrogenase deficiency.
• Patients with evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) ≤6 months prior to Day 1 of treatment.
• Any known positive test for human immunodeficiency virus, hepatitis C virus or acute or chronic hepatitis B infection.
• Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
• Use of any non-approved or investigational agent ≤28 days or 5 half-lives prior to administration of the first dose of study drug, whichever is shorter.
• Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g. active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
• Inability to swallow whole capsules.

PHASE I ONLY

•Patients who have had radiation therapy, hormonal therapy, biologic therapy, investigational agents, or chemotherapy for cancer within 28 days or 5 half-lives of the chemotherapy or biologic/targeted agents, whichever is shorter, prior to Day 1 of the study.

PHASE II ONLY

•Past or current history of neoplasm other than the entry diagnosis with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other cancers cured by local therapy alone and a disease free survival ≥5 years.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: collaborator

SCRI Development Innovations, LLC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johanna C Bendell, M.D.

Role: STUDY_CHAIR

SCRI Development Innovations, LLC

Locations

Yale University School of Medicine

New Haven, Connecticut, United States

Florida Cancer Specialists-South

Fort Myers, Florida, United States

Florida Cancer Specialists-Sarasota

Sarasota, Florida, United States

Florida Cancer Specialists-North

St. Petersburg, Florida, United States

Oklahoma University

Oklahoma City, Oklahoma, United States

South Carolina Oncology Associates

Columbia, South Carolina, United States

Tennessee Oncology - Chattanooga

Chattanooga, Tennessee, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Center for Cancer and Blood Disorders

Fort Worth, Texas, United States

Countries

United States

Other Identifiers

SCRI GI 157

Identifier Type: -

Identifier Source: org_study_id