Tivantinib With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Locally Advanced Kidney Cancer That Cannot Be Removed by Surgery
Condition: 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
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Erlotinib Hydrochloride; Laboratory Biomarker Analysis; Tivantinib
Intervention description: 150 mg (1 tablet) by mouth on days 1-28, once daily, until disease progression; Correlative studies; 360 mg (3 tablets) by mouth, Twice daily (720 mg total daily dose) on days 1-28, until disease progression
Intervention MeSH terms: Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 55.0
Sex: All
Healthy volunteers: No

Summary:

      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.
    

Eligibility 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