Tivantinib in Treating Younger Patients With Relapsed or Refractory Solid Tumors

NCT01725191 | Completed Phase 1

• 4 other identifiers: NCI-2012-02163COG-ADVL1111ADVL1111U01CA097452
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 20

Brief Summary

This phase I trial studies the side effects and best dose of tivantinib in treating younger patients with solid tumors that have returned after a period of improvement or have not responded to treatment. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Childhood Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• MTD defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  28 days

• Pharmacokinetic (PK) parameters of tivantinib

  The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

  Pre-dose, 1, 2, 4, 6 and 8-12 hours day 1 of course 1; pre-dose day 1 of course 2

Secondary Outcomes (1)

• Disease response assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria

  Up to 30 days after completion of study treatment

Other Outcomes (2)

• CYP450 polymorphisms

  Baseline

• Tumor c-met expression

  Baseline

Study Arms (1)

Treatment (tivantinib)

EXPERIMENTAL

Patients receive tivantinib PO BID on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Tivantinib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (tivantinib)

Pharmacological Study OTHER

Correlative studies

Treatment (tivantinib)

Tivantinib DRUG

Given PO

Also known as: ARQ 197, ARQ-197, c-Met Inhibitor ARQ 197

Treatment (tivantinib)

Eligibility Criteria

• Age: 13 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• PART A: Patients on dose levels -1 or 1 must have a body surface area (BSA) \>= 0.65 m\^2 at the time of study enrollment; patients on dose levels 2 or 3 must have a BSA \>= 0.45 m\^2 at the time of study enrollment
• PART B: There is no minimum body surface area requirement for patients in part B
• Patients with relapsed or refractory solid tumors including central nervous system (CNS) tumors are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
• Patients must have either measurable or evaluable disease
• Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age; note: neurologic deficits in patients with CNS tumors must have been stable or improving for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy:
• Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
• Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
• Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
• Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
• Radiation therapy (XRT): At least 14 days after local palliative XRT (small port); at least 150 days must have elapsed if prior total-body irradiation (TBI), craniospinal XRT or if \>= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
• Stem cell infusion without TBI: No evidence of active graft vs. host disease and at least 84 days must have elapsed after transplant or stem cell infusion
• Patients may not have received prior therapy with tivantinib

You may not qualify if:

• Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients must not be receiving any of the following for at least 24 hours prior to enrollment: omeprazole, esoprazole, lansoprazole, pantoprazole, rifampin, omeprazole, fluvoxamine, or moclobemide
• Patients must not be receiving any of the following for at least 24 hours prior to enrollment: atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, rifampicin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, or St. John's Wort
• Nasogastric or G tube administration is not allowed; patients in part A must be able to swallow capsules
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
• Patients with \>= grade 2 bradycardia or with a known history \>= grade 2 cardiac arrhythmia are not eligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (20)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Childrens Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, 30322, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

MeSH Terms

Interventions

ARQ 197

Study Officials

• James Geller

  COG Phase I Consortium

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 8, 2012
• First Posted: November 12, 2012
• Study Start: October 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: July 2, 2015

Record last verified: 2015-05

Locations

CA (1); US (19)