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Tivantinib With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Locally Advanced Kidney Cancer That Cannot be Removed by Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01688973
First received: September 14, 2012
Last updated: November 25, 2014
Last verified: November 2014
  Purpose

This randomized phase II trial studies how well tivantinib with or without erlotinib hydrochloride works in treating patients with metastatic or locally advanced kidney cancer that cannot be removed by surgery. Tivantinib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Childhood Renal Cell Carcinoma
Recurrent Renal Cell Carcinoma
Stage III Renal Cell Cancer
Stage IV Renal Cell Cancer
Type 1 Papillary Renal Cell Carcinoma
Type 2 Papillary Renal Cell Carcinoma
Drug: Tivantinib
Drug: Erlotinib Hydrochloride
Other: Laboratory Biomarker Analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Parallel (Randomized) Phase II Evaluation of ARQ 197 and ARQ 197 in Combination With Erlotinib in Papillary Renal Cell Carcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Response rate (confirmed complete response or partial response), determined according to Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Frequency and severity of toxicities, graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Summarized by arm by examining the frequency and severity of toxicities, the frequency and extent of required dose modifications, and the frequency and cause of patient withdrawal for reasons other than progression.

  • PFS [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Role of c-MET [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Explored through the use of Cox regression, categorical analysis (responders/non-responders versus high expressors, etc.), and graphical presentations.

  • Role of EGFR [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Explored through the use of Cox regression, categorical analysis (responders/non-responders versus high expressors, etc.), and graphical presentations.


Estimated Enrollment: 78
Study Start Date: August 2012
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (tivantinib)
Patients receive tivantinib PO BID on days 1-28.
Drug: Tivantinib
Given PO
Other Names:
  • ARQ 197
  • ARQ-197
  • c-Met Inhibitor ARQ 197
Other: Laboratory Biomarker Analysis
Correlative studies
Experimental: Arm II (tivantinib and erlotinib hydrochloride)
Patients receive tivantinib PO BID and erlotinib hydrochloride PO QD on days 1-28.
Drug: Tivantinib
Given PO
Other Names:
  • ARQ 197
  • ARQ-197
  • c-Met Inhibitor ARQ 197
Drug: Erlotinib Hydrochloride
Given PO
Other Name: Cp-358,774
Other: Laboratory Biomarker Analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the response rate (confirmed complete and partial response) of patients with locally advanced or metastatic papillary renal cell carcinoma treated with either ARQ 197 (tivantinib) or ARQ 197 combined with erlotinib (erlotinib hydrochloride).

SECONDARY OBJECTIVES:

I. To assess the progression free survival (PFS) of patients with locally advanced or metastatic papillary renal cell carcinoma treated with either ARQ 197 or ARQ 197 combined with erlotinib.

II. To assess the safety and tolerability of ARQ 197 therapy and ARQ 197 combined with erlotinib.

III. To descriptively assess the role of prior treatment on outcome.

TERTIARY OBJECTIVES:

I. To bank tissue specimens for future use and once funding is obtained to evaluate the expression of tissue correlative biomarkers such as hepatocyte growth factor receptor (c-MET) and epidermal growth factor receptor (EGFR), and to perform exploratory correlation with clinical outcomes.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive tivantinib orally (PO) twice daily (BID) on days 1-28.

ARM II: Patients receive tivantinib PO BID and erlotinib hydrochloride PO once daily (QD) on days 1-28.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for up to 2 years.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed papillary histology renal cell carcinoma which is metastatic, or locally advanced and unresectable; mixed histologies will be allowed provided that they contain >= 50% of the papillary component
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension; x-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; x-rays, scans or physical examinations for non-measurable disease must have been completed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment form
  • Patients with metastatic disease who have a resectable primary tumor and are deemed a surgical candidate may have undergone resection; at least 28 days must have elapsed since surgery and patient must have recovered from any adverse effects of surgery
  • Patients with a history of brain metastases who are asymptomatic and have not received steroid therapy in the 14 days prior to registration are eligible; anti-seizure medications are allowed provided they are non-enzyme inducing (e.g. topiramate, levetiracetam, gabapentin)
  • Patients may have received up to one prior systemic therapy for advanced or metastatic renal cell carcinoma; patients must not have received a MET inhibitor or erlotinib as prior therapy; at least 21 days must have elapsed since completion of prior systemic therapy, 42 days for nitrosoureas or mitomycin C; patients must have recovered from all associated toxicities at the time of registration
  • Patients may have received prior radiation therapy, but must have measurable disease outside the radiation port; at least 21 days must have elapsed since completion of prior radiation therapy; patients must have recovered from all associated toxicities at the time of registration
  • Patients must not be receiving or planning to receive any other investigational agents
  • Patients must have a complete physical examination and medical history within 28 days prior to registration
  • Patients must have a Zubrod performance status of 0-2
  • White blood cell (WBC) >= 2,000/mcL
  • Absolute neutrophil count (ANC) >= 1,000/mcL
  • Platelet count >= 75,000/mcL
  • Serum bilirubin =< 1.5 x institutional upper limits of normal (ULN)
  • Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) and serum glutamic pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) must be =< 1.5 x the institutional ULN unless the liver is involved with the tumor, in which case serum transaminase (SGOT/SGPT) must be =< 5 x the institutional ULN
  • Serum creatinine must be =< 2 x the institutional ULN
  • Sodium, potassium and calcium must be obtained within 14 days prior to registration
  • Patients with a known history of the following corneal diseases are not eligible: dry eye syndrome, Sjogren's syndrome, keratoconjunctivitis sicca, exposure keratopathy, Fuchs' dystrophy or other active disorders of cornea
  • Patients known to be human immunodeficiency virus (HIV)-positive and receiving combination anti-retroviral therapy are not eligible
  • Patients must be able to take oral medications; patients must not have gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease; patients with intractable nausea or vomiting are not eligible
  • Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
  • Patients must be offered the opportunity to participate in specimen banking for future translational medicine studies
  • All patients must be informed of the investigational nature of this study and must sign and give written informed consent
  • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01688973

  Show 216 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Przemyslaw Twardowski Southwest Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01688973     History of Changes
Other Study ID Numbers: NCI-2012-01641, NCI-2012-01641, SWOG-S1107, S1107, S1107, U10CA032102, U10CA180888
Study First Received: September 14, 2012
Last Updated: November 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Adenocarcinoma
Kidney Diseases
Kidney Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Erlotinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on November 27, 2014