Sorafenib Tosylate and Hypoxia-Activated Prodrug TH-302 in Treating Patients with Advanced Kidney Cancer or Liver Cancer that Cannot be Removed by Surgery

  • Study type:

    Interventional What is this?

    Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • Study phase:

    I/II What is this?

    During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

Study IDs

  • Site IRB:

    • Scottsdale/Phoenix, Arizona: 11-007034
    • Rochester, Minnesota: 11-007034
    • Jacksonville, Florida: 11-007034
  • NCT ID:

    NCT01497444
  • Sponsor Protocol Number:

    N1153

About this study

RATIONALE: Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth by blocking blood flow to the tumor. Drugs used in chemotherapy, such as hypoxia-activated prodrug TH-302, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib tosylate together with hypoxia-activated prodrug TH-302 may kill more tumor cells.

PURPOSE: This phase I/II trial studies the side effects and best dose of giving sorafenib tosylate together with hypoxia-activated prodrug TH-302 and to see how well they work in treating patients with advanced kidney cancer or liver cancer that cannot be removed by surgery.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

DISEASE CHARACTERISTICS:

  • Cytologically or histologically confirmed diagnosis of advanced hepatocellular carcinoma (HCC) or renal cell carcinoma; HCC patients should not be amenable to treatment with surgery or to orthotopic liver transplant (phase I)
  • Cytologically or histologically confirmed diagnosis of hepatocellular carcinoma that is locally advanced or metastatic and is not amenable to treatment with surgery or to orthotopic liver transplant (phase II)
  • Patients must have measurable disease
  • HCC patients only:
    • Advanced HCC after first-line (i.e., no prior systemic therapy) or second-line (with prior first-line sorafenib tosylate therapy only) treatment (phase I)
    • Advanced HCC after first-line treatment (i.e., no prior systemic therapy) (phase II)
    • Child Pugh class A or B7 liver disease
    • Prior chemoembolization, radioembolization, radiofrequency ablation (RFA), or other local ablative therapies are permissible if ≥ 6 weeks from procedure with evidence of progression or new metastatic disease, if applicable
  • No known central nervous system (CNS) or brain metastasis that is either symptomatic or untreated
    • Patients with neurological symptoms must undergo a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis
    • Patients with CNS metastases that have been treated and are stable without symptoms for ≥ 4 weeks after completion of treatment are eligible
  • HCC patients only: cancer potentially amenable to local modalities of therapy or surgical resection not allowed
  • No fibrolamellar histology HCC, mixed hepatocholangiocarcinoma, hepatic sarcomas, and other non-HCC primary liver tumors

PATIENT CHARACTERISTICS:

  • ECOG performance status 0 or 1
  • Life expectancy ≥ 3 months
  • Absolute neutrophil count ≥ 1,200/mm³
  • Peripheral platelet count ≥ 75,000/mm³
  • Hemoglobin > 8.5 g/dL
  • Total bilirubin ≤ 3.0 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN (if patient has HCC or liver metastases, then ≤ 5 times ULN) (phase I)
  • Creatinine ≤ 1.5 times ULN
  • International normalized ratio (INR) ≤ 1.5 times ULN
  • Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only
  • Willing to return to North Central Cancer Treatment Group (NCCTG) enrolling institution for follow-up
  • Ability to receive intravenous contrast for the purpose of imaging (phase II)
  • None of the following:
    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception for the duration of study participation; men and women should continue to use adequate birth control after the last administration of sorafenib tosylate and hypoxia-activated prodrug TH-302 (TH-302) under the guidance of their treating physician
  • No co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • No other active malignancy ≤ 3 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history or prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
  • No inadequately controlled hypertension (systolic blood pressure of > 150 mm Hg or diastolic pressure > 100 mm Hg on anti-hypertensive medications)
  • No New York Heart Association (NYHA) classification III or IV congestive heart failure
  • No known or suspected allergy or hypersensitivity to any component of TH-302, sorafenib tosylate, or any of the sorafenib tosylate excipients
  • No condition that severely impairs patient's ability to swallow whole pills
  • No QTc interval > 500 msec on baseline electrocardiogram (EKG)
  • No documented history of prolonged QTc interval ≤ 6 months prior to registration
  • No traumatic injury in the past 14 days

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Not receiving any other investigational agent
  • No major surgical procedures prior to registration or anticipation of need for elective or planned major surgical procedure during the course of the study
  • No treatment with radiation therapy or investigational therapy ≤ 28 days prior to registration
  • RCC patients only: No chemotherapy prior to study entry within 5 half-lives of the agent (as described in the package insert), or 4 weeks prior to registration (whichever is shorter) with resolution of side effects from therapy to ≤ grade 1
  • No medication that has documented data or is generally accepted as having increased risk of QT prolongation and/or Torsades de Pointes
  • Not receiving any medications or substances that are inducers or strong or moderate inhibitors of CYP3A4 ≤ 7 days prior to registration
  • Patients receiving anti-coagulation therapy are permitted as long as they have a stable INR ≤ 3.0

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Mitesh Borad, M.D.

Contact us for the latest status

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Mitesh Borad, M.D.

Contact us for the latest status

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Mitesh Borad, M.D.

Contact us for the latest status

Cancer Center Clinical Trials Referral Office

855-776-0015