Navitoclax and Sorafenib Tosylate in Treating Patients With Relapsed or Refractory Solid Tumors

Overview

  • Study type

    Interventional
  • Study phase

    I
  • Study IDs

  • 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.
  • 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.

  • Site IRB
    • Scottsdale/Phoenix, Arizona: 14-007730
    • Jacksonville, Florida: 14-007730
    • Rochester, Minnesota: 14-007730
    NCT ID: NCT02143401
    Sponsor Protocol Number: MC1315

About this study

This phase I trial studies the side effects and the best dose of navitoclax when given together with sorafenib tosylate in treating patients with solid tumors that have returned (relapsed) or do not respond to treatment (refractory). Navitoclax and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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

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
  • HCC patients only: HCC confirmed by biopsy OR diagnosed by clinical and radiologic criteria; all of the following criteria must be met or a biopsy is required:
    • Known cirrhosis or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
    • Hypervascular liver masses > 2 cm, and either serum alpha-fetoprotein (AFP) > 400 ng/ml
    • AFP > three times normal and doubling in value in the antecedent 3 months
    • In the expansion cohort, prior treatment with sorafenib as first-line therapy allowed
  • Any number of the following prior therapies is allowed:
    • Chemotherapy >= 28 days prior to registration
    • Mitomycin C/nitrosoureas >= 42 days prior to registration
    • Immunotherapy >= 28 days prior to registration
    • Biologic therapy >= 28 days prior to registration
    • Radiation therapy >= 28 days prior to registration
    • Radiation to < 25% of bone marrow
  • HCC patients only: prior regional treatments for liver metastasis are permitted including:
    • Selective internal radiation therapy such as brachytherapy, CyberKnife, radiolabeled microsphere embolization, etc.
    • Hepatic artery chemoembolization
    • Hepatic artery embolization
    • Hepatic artery infusional chemotherapy
    • Radiofrequency ablation
    • NOTE: patients must be >= 4 weeks from treatment and show progressive disease in the liver after regional therapy or must have measurable disease outside the liver
  • HCC patients only: Child Pugh class A or B7 liver disease
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Life expectancy of > 3 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL (subjects may be treated with hematopoietic growth factors to achieve or maintain this level)
  • Hemoglobin >= 9.0 g/dL
  • International normalized ratio (INR) =< 1.4
  • Platelets >= 100,000/mm^3
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (patients with Gilbert's syndrome may have serum bilirubin > 1.5 x ULN) (NOTE: If patient has liver involvement by tumor, total bilirubin must be within normal range)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (NOTE: If patient has liver involvement by tumor, AST/ALT must be within normal range)
  • Serum creatinine =< 1.5 times the ULN
  • Able to swallow and retain oral medication
  • Negative serum pregnancy test =< 7 days prior to registration for women of childbearing potential
    • NOTE: women will be considered not of childbearing potential if they are surgically sterile (bilateral oophorectomy or hysterectomy) and/or post-menopausal (amenorrheic for at least 12 months)
  • Ability to understand and the willingness to sign a written informed consent document
  • Willing to provide tissue samples for correlative research purposes

Exclusion Criteria:

  • Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v 4.0) grade 2 or higher from previous anti-cancer therapy, except alopecia
  • Receiving any other investigational agents =< 28 days prior to registration
  • Known brain metastases (even if treated)
  • Known portal hypertension or history of variceal bleeding
  • Inadequately controlled hypertension (systolic blood pressure of > 150 mmHg or diastolic pressure > 90 mmHg on anti-hypertensive medications)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to navitoclax or sorafenib
  • Current use of anticoagulation; NOTE: use of low-dose anticoagulation medications (such as heparin) that are used to maintain the patency of a central intravenous catheter is allowed
  • Corrected QT (QTc) interval > 480 msec on baseline electrocardiogram (EKG)
  • Documented history of prolonged QTc interval =< 6 months prior to registration
  • Receiving any medications that prolong the QTc and have a known risk for Torsades de pointes; providers should use caution with drugs with possible increased risk for Torsades de pointes; NOTE: patient will be eligible if they can be taken off these medications prior to initiation of therapy and no less than 4 half-lives of the medication
  • Current use of certain concomitant medications due to mechanistic-based platelet toxicities from navitoclax: clopidogrel, ibuprofen, tirofiban and other anticoagulants, drugs or herbal supplements that effect platelet function; NOTE: antiplatelet use is prohibited during the use of navitoclax; subjects who have previously received aspirin therapy for thrombosis prevention may resume a low dose (i.e., maximum 100 mg QD) of aspirin if platelet counts are stable (>= 50,000/mm^3) through 6 weeks of navitoclax administration; all decisions regarding treatment with aspirin therapy will be determined by the principal investigator in conjunction with the medical monitor
  • Current use of strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors such as ketoconazole, itraconazole, voriconazole, posaconazole, nefazodone, and clarithromycin are prohibited; NOTE: moderate inhibitors of CYP3A4 should be used with caution; navitoclax is a moderate inhibitor of ytochrome P450 family 2 subfamily C (CYP2C)8 and a strong inhibitor of CYP2C9; caution should be exercised when dosing navitoclax concurrently with CYP2C8 and CYP2C9 substrates; common CYP2C8 substrates include paclitaxel, statins and repaglinide; CYP2C9 substrates include celecoxib, phenytoin and warfarin; when possible, investigators should switch to alternative medications or monitor the patients closely
  • Concurrent use of strong CYP3A4/5 inducers such as carbamazepine, phenytoin, rifampin, and St. John's wort are prohibited
  • 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
  • Any of the following:
    • Pregnant women
    • Nursing women
    • Women of childbearing potential who are unwilling to employ adequate contraception; NOTE: 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; women of child-bearing potential and men must agree to use adequate contraception using one of the methods listed below prior to study entry, for the duration of study participation, and up to 90 days following completion of therapy:
      • Total abstinence from sexual intercourse (minimum one complete menstrual cycle prior to study drug administration)
      • Vasectomized male subject or vasectomized partner of female subjects
      • Hormonal contraceptives (oral, parenteral, transdermal or vaginal ring) for at least 3 months prior to study drug administration; if the subject is currently using a hormonal contraceptive, she should also use a barrier method during this study and for 1 month after study completion
      • Intrauterine device (IUD)
      • Double-barrier method: male condom plus diaphragm or vaginal cap with spermicide (contraceptive sponge, jellies or creams)
      • Additionally, male subjects (including those who are vasectomized) whose partners are pregnant or might be pregnant must agree to use condoms for the duration of the study and for 90 days following completion of therapy
  • Human immunodeficiency virus (HIV)-positive patients on highly active antiretroviral therapy (HAART) are excluded
  • Underlying condition predisposing them to bleeding or currently exhibits signs of clinically significant bleeding
  • Recent history of non-chemotherapy-induced thrombocytopenic-associated bleeding =< 1 year prior to the registration
  • History of cardiovascular disease (e.g., myocardial infraction [MI], thrombotic or thromboembolic event in the last 6 months)

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

Brian Costello, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Brian Costello, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Brian Costello, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015