Trial record 1 of 1 for:    ARQ 197 + Topotecan
Previous Study | Return to List | Next Study

Tivantinib and Topotecan Hydrochloride in Treating Patients With Advanced or Metastatic Solid Tumors or Recurrent Small Cell Lung Cancer

This study is currently recruiting participants.
Verified March 2013 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01654965
First received: July 30, 2012
Last updated: March 18, 2013
Last verified: March 2013
  Purpose

This phase I trial studies the side effects and best dose of tivantinib given together with topotecan hydrochloride in treating patients with advanced or metastatic solid tumors or recurrent small cell lung cancer. Tivantinib and topotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth


Condition Intervention Phase
Recurrent Small Cell Lung Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: tivantinib
Drug: topotecan hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
Other: pharmacogenomic studies
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of ARQ 197 in Combination With IV Topotecan in Advanced Solid Tumors With an Expansion Cohort in Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Toxicities, graded according to the NCI CTCAE version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
    The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by CTCAE), attribution, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.


Secondary Outcome Measures:
  • Tumor response as evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    All responses will be reported; because of the potential heterogeneity of the patients, no attempt will be made to summarize these. For patients with small cell lung cancer (SCLC) treated at the RP2D, the response rate will be estimated in 2 ways: (1) primary analysis will include all eligible patients who began treatment, and (2) a secondary analysis will include eligible patients who completed 2 courses or who came off treatment for disease progression prior to completing the second course.

  • Progression-free survival (PFS) [ Time Frame: The time from start of treatment until first evidence of disease progression or death due to any cause, assessed up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    PFS will be reported for all patients. For patients with SCLC, PFS summarized using standard descriptive statistics (Kaplan-Meier plots with point estimates and standard errors at 6, 12, and 18 months). Patients will be classified by their response to first-line platinum-based chemotherapy. For patients who had progression of their cancer 90 days after completion of platinum-based chemotherapy will be classified as having "platinum-refractory" disease; patients with progression 90 days after completion of platinum-based chemotherapy will be classified as having "platinum-sensitive" disease."

  • Overall survival (OS) [ Time Frame: The time from start of treatment until death due to any cause, assessed up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    OS will be reported for all patients. For patients with SCLC, OS will be summarized using standard descriptive statistics (Kaplan-Meier plots with point estimates and standard errors at 6, 12, and 18 months).


Estimated Enrollment: 34
Study Start Date: July 2012
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (tivantinib and topotecan hydrochloride)
Patients receive tivantinib PO BID on days 1-21 and topotecan hydrochloride IV over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: tivantinib
Given PO
Other Name: ARQ 197
Drug: topotecan hydrochloride
Given IV
Other Names:
  • hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • TOPO
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study

Detailed Description:

OBJECTIVES:

I. To establish the recommended phase 2 dose (RP2D) for the combination of ARQ 197 (tivantinib) and intravenous (IV) topotecan (topotecan hydrochloride).

II. To describe the toxicities of ARQ 197 and IV topotecan at each dose studied.

III. To characterize the pharmacokinetic behavior of ARQ 197 given concurrent use of IV topotecan.

IV. To obtain preliminary information regarding the effect of ARQ 197 and IV topotecan on met proto-oncogene (hepatocyte growth factor receptor) (c-Met) and focal adhesion kinase (FAK) phosphorylation in circulating tumor cells and in tumor biopsies.

V. To document all clinical responses to ARQ 197 with IV topotecan.

OUTLINE: This is a dose-escalation study of tivantinib and topotecan hydrochloride.

Patients receive tivantinib orally (PO) twice daily (BID) on days 1-21 and topotecan hydrochloride IV over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; for the expansion group, patients must have histologically or cytologically confirmed small cell lung cancer previously treated with one or more chemotherapy or chemoradiotherapy regimens, at least one of which must have been platinum-based
  • Karnofsky >= 60%
  • Life expectancy of greater than 12 weeks
  • Hemoglobin >= 9.0 g/dL
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 X institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal (=< 5 X institutional upper limit of normal if the rise can be attributed to liver metastases)
  • Serum creatinine =< 1.5 X institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ARQ 197 administration
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who are receiving any other investigational agents
  • Patients with untreated brain metastases should be excluded from this clinical trial; however patients with stable brain disease (off corticosteroids) at least 2 weeks after completion of appropriate therapy for their brain metastases are eligible; patients who require enzyme-inducing anti-convulsants (EIAC) should be switched to non-EIAC and be on a stable dose of the new agent for at least 2 weeks prior to treatment on this protocol
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ARQ 197 or topotecan
  • The metabolism and consequently overall pharmacokinetics of ARQ 197 could be altered by inhibitors and/or inducers or other substrates of cytochrome P450 2C19 (CYP2C19) and cytochrome P450 3A4 (CYP3A4); while inhibitors/inducers of these cytochrome P450 isoenzymes are not specifically excluded, investigators should be aware that ARQ 197 exposure may be altered by the concomitant administration of these drugs; caution should be applied when CYP2C19 inhibitors such as omeprazole, fluvoxamine, fluconazole, ticlopidine, rabeprazole, fluoxetine, and moclobemide, or strong CYP3A4 inhibitors such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, ciprofloxacin, telithromycin, troleandomycin (TAO), or voriconazole, are used as concomitant therapy; because the lists of these agents are changing, it is important to consult an updated list; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • History of congestive heart failure defined as class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); clinically significant bradycardia or other uncontrolled, cardiac arrhythmia defined as >= grade 3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, or uncontrolled hypertension; myocardial infarction occurring within 6 months prior to study entry (myocardial infarction occurring > 6 months prior to study entry is permitted)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ARQ 197
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Patients previously treated with topotecan are ineligible
  • Patients previously treated with ARQ 197 are ineligible
  • Patients unable to swallow ARQ 197 pills are ineligible
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01654965

Locations
United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Stephen V. Liu     323-865-3900     stephen.liu@usc.edu    
Principal Investigator: Stephen V. Liu            
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Barbara J. Gitlitz     323-865-3900     gitlitz@usc.edu    
Principal Investigator: Barbara J. Gitlitz            
UC Davis Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: David R. Gandara     916-734-3771     david.gandara@ucdmc.ucdavis.edu    
Principal Investigator: David R. Gandara            
United States, Pennsylvania
Penn State Milton S Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033-0850
Contact: Chandra P. Belani     717-531-1078     cbelani@psu.edu    
Principal Investigator: Chandra P. Belani            
University of Pittsburgh Cancer Institute Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Ahmad A. Tarhini     412-648-6507     tarhiniaa@upmc.edu    
Principal Investigator: Ahmad A. Tarhini            
Sponsors and Collaborators
Investigators
Principal Investigator: Stephen Liu City of Hope Medical Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01654965     History of Changes
Other Study ID Numbers: NCI-2012-01220, PHI-68, U01CA062505
Study First Received: July 30, 2012
Last Updated: March 18, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Topotecan
Lung Neoplasms
Small Cell Lung Carcinoma
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 19, 2013