NCT01611857

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
49

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jul 2012

Typical duration for phase_1

Geographic Reach
1 country

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 1, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

June 5, 2012

Completed
26 days until next milestone

Study Start

First participant enrolled

July 1, 2012

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2015

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2015

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

November 23, 2016

Completed
Last Updated

November 23, 2016

Status Verified

October 1, 2016

Enrollment Period

3 years

First QC Date

June 1, 2012

Results QC Date

August 9, 2016

Last Update Submit

October 3, 2016

Conditions

Malignant Solid TumourGastroesophageal Cancer

Keywords

Advanced solid tumorsFirst-Line Metastatic GE cancerc-Met InhibitorTivantinibFOLFOX

Outcome Measures

Primary Outcomes (1)

  • The Incidence of Dose Limiting Toxicities (DLT) in Phase I Dose Escalation

    Using a standard 3+3 design participants were enrolled in dose-escalating cohorts to determine the maximum tolerated dose (MTD) of tivantinib when given with FOLFOX (5-FU 400 mg/m\^2, continuous IV 5-FU 2400 mg/m\^2 over 46 hours, leucovorin 400 mg/m\^2 IV, and oxaliplatin 85 mg/m\^2). MTD is defined as the highest dose level at which no more than 1 of 6 patients experiences a DLT, assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.

    14 Days (1 cycle)

Secondary Outcomes (3)

  • Progression Free Survival in Phase II Dose Expansion

    every 8 weeks until treatment discontinuation, projected 18 months and then every 3 months thereafter up to 5 years from start of treatment.

  • Overall Survival in Phase II Dose Expansion

    every 8 weeks until treatment discontinuation, an expected average of 18 months, then every 12 weeks thereafter up to 5 years from start of treatment.

  • Time to Progression in Phase II Dose Expansion

    every 8 weeks until progressive disease, expected 18 months.

Study Arms (1)

Maximum Tolerated Dose

EXPERIMENTAL

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.

Drug: TivantinibDrug: FOLFOX

Interventions

TivantinibDRUG

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.

Also known as: ARQ 197
Maximum Tolerated Dose
FOLFOXDRUG

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.

Also known as: 5-FU, Leucovorin, Oxaliplatin, Levoleucovorin, 5-Fluorouracil
Maximum Tolerated Dose

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +5 more criteria

You may not qualify if:

  • 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.
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

Florida Cancer Specialists-South

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialists-Sarasota

Sarasota, Florida, 34232, United States

Location

Florida Cancer Specialists-North

St. Petersburg, Florida, 33705, United States

Location

Oklahoma University

Oklahoma City, Oklahoma, 73104, United States

Location

South Carolina Oncology Associates

Columbia, South Carolina, 29210, United States

Location

Tennessee Oncology - Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

MeSH Terms

Interventions

ARQ 197Folfox protocolFluorouracilLeucovorinOxaliplatinLevoleucovorin

Intervention Hierarchy (Ancestors)

UracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingCoenzymesEnzymes and CoenzymesCoordination ComplexesOrganic Chemicals

Results Point of Contact

Title
Charles H. Davis
Organization
Sarah Cannon Research Institute
charles.davis2@scri-innovations.com
615-524-4341

Study Officials

  • Johanna C Bendell, M.D.

    SCRI Development Innovations, LLC

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

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

June 1, 2012

First Posted

June 5, 2012

Study Start

July 1, 2012

Primary Completion

July 1, 2015

Study Completion

August 1, 2015

Last Updated

November 23, 2016

Results First Posted

November 23, 2016

Record last verified: 2016-10

Locations

US(9)