Clinical trial NCT03323710 (phase 2, status: withdrawn)
Conditions: renal cell carcinoma
ICD codes: C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8
Drugs: propranolol, sunitinib
SMILES: COCCC1=CC=C(OCC(O)CNC(C)C)C=C1, CNC(=O)C1=C(SC2=CC=C3C(NN=C3\C=C\C3=CC=CC=N3)=C2)C=CC=C1
Reason stopped: 
    poor patient recruitment.
  
Eligibility criteria:

        Inclusion Criteria:

        Patients are eligible to be included in the study only if they meet all of the following
        criteria:

          1. Histological diagnosis of clear-cell renal cell carcinoma (RCC) or mixed-type RCC with
             more than 60% of clear-cell component.

          2. Diagnosis of stage IV RCC (primary metastatic or recurrence after surgical procedure).

          3. Prior nephrectomy (complete or partial).

          4. Presence of measurable disease per Response Evaluation Criteria in Solid Tumors
             version 1.1.

          5. Karnofsky performance status score of 80-100%.

          6. Favourable- or intermediate-risk according to Memorial Sloan Kettering Cancer Center
             criteria.

          7. Adequate organ function, including the following:

               1. hepatic: total bilirubin ≤ 2 times the upper limit of normal (excluding patients
                  with Gilbert syndrome), aspartate aminotransferase and alanine aminotransferase ≤
                  5 times the upper limit of normal,

               2. renal: serum creatinine ≤ 2 times the upper limit of normal,

               3. bone marrow: absolute neutrophil count ≥ 1500/mm3, platelets ≥ 100000/mm3,
                  hemoglobin ≥ 9.5 g/dl.

          8. Normal thyroid function (natural or with supplementation of thyroid hormones) defined
             as thyroid-stimulating hormone within limits of normal.

          9. Age eighteen years or older on the day of consent.

         10. Written informed consent prior to study entry.

        Exclusion Criteria:

        Patients will be excluded from the study if they meet any of the following criteria:

          1. Prior systemic pharmacotherapy of RCC.

          2. Treatment with propranolol within 6 months of study entry.

          3. Metastases in central nervous system (patients who had central nervous system
             metastases that were surgically resected and/or treated with radiotherapy in the past
             and now are without neurological symptoms, are allowed on protocol).

          4. Female patients who are pregnant or breast feeding or adults of reproductive potential
             who are not using effective birth control methods.

          5. Presence of other malignancies (patients with carcinoma in situ of the cervix or basal
             cell carcinoma of the skin are allowed on protocol).

          6. Presence of any severe and/or uncontrolled medical conditions or other conditions that
             could affect their participation in the study such as:

               1. heart failure of New York Heart Association Class III or IV, significant cardiac
                  arrhythmia or any other clinically significant cardiovascular disease,

               2. unstable angina pectoris, symptomatic congestive heart failure, myocardial
                  infarction within 6 months of entering the study,

               3. severely impaired respiration as defined as O2 saturation that is ≤ 90% at rest
                  on room air,

               4. uncontrolled diabetes as defined by fasting serum glucose > 1.5 times the upper
                  limit of normal,

               5. ejection fraction less than 40% (measured at echocardiography),

               6. significant liver disease such as cirrhosis, active hepatitis or chronic
                  persistent hepatitis,

               7. active (acute or chronic) infections requiring antimicrobial intervention.

          7. Concomitant treatment with:

               1. chronic, systemic corticosteroids or another immunosuppressive agent; topical or
                  inhaled corticosteroids are allowed,

               2. strong CYP3A4 inducers/inhibitors: carbamazepine, phenytoin, rifabutin, rifampin,
                  nafcillin, phenobarbital, St John's wort, itraconazole, ketoconazole,
                  erythromycin, clarithromycin, nefazodone.

          8. Known allergy/sensitivity to sunitinib and/or propranolol.

          9. Galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

         10. Immunization with attenuated live vaccines within 30 days of study entry.

         11. Human immunodeficiency virus sero-positivity at the study entry or in the past.

         12. Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of sunitinib and/or propranolol (e.g., ulcerative
             disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small
             bowel resection).

         13. Presence of active, bleeding diathesis.

         14. Major surgery (defined as requiring general anesthesia) and/or significant traumatic
             injury (requiring > 28 days to heal) within 28 days of the study entry; presence of
             side effects due to any surgery or probable requirement of major surgery during the
             course of the study.

         15. Present contraindications to propranolol, that include: bronchial asthma, prolonged
             fasting, acidosis, hypotension (systolic blood pressure less than 90 mmHg, diastolic
             blood pressure less than 60 mmHg), severe peripheral arterial circulatory disturbance,
             cardiogenic shock, bradycardia, Prinzmetal's angina, uncontrolled heart failure,
             second or third degree heart block, untreated phaeochromocytoma, sick sinus syndrome.

         16. Inability or unwillingness of subject or legal guardian/representative to give written
             informed consent.