Clinical trial NCT04437953 (phase 2, status: withdrawn)
Conditions: thrombocytopenia, cancer, liver diseases
ICD codes: D69.6, D69.49, D69.59, P61.0, D75.82, D69.42, O36.8211, C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2, K76.9, K71.8, K70.9, K71.9, K75.9, P78.84, Q44.6
Drugs: avatrombopag
SMILES: OC(=O)C1CCN(CC1)C1=C(Cl)C=C(C=N1)C(=O)NC1=NC(C2=CC(Cl)=CS2)=C(S1)N1CCN(CC1)C1CCCCC1
Reason stopped: 
    lack of accrual
  
Eligibility criteria:

        Inclusion Criteria:

          -  Patients with history of locally advanced or metastatic solid tumor, with a plan to
             initiate cancer directed systemic therapy for adjuvant or palliative purposes.

          -  18 years of age or greater

          -  Known liver disease attributed to one of the following:

               1. Chronic HBV and/or chronic HCV with Cirrhosis

               2. Alcoholic Cirrhosis

               3. Nonalcoholic Fatty Liver Disease with Cirrhosis

               4. Primary Biliary Cholangitis

               5. Primary Sclerosing Cholangitis

               6. Autoimmune Hepatitis

               7. Hereditary Hemochromatosis

               8. Wilsons Disease

               9. Alpha-1 Antitrypsin Deficiency

              10. Congestive Hepatopathy

              11. Cirrhosis or known pre-existing liver dysfunction of unknown cause, or not
                  otherwise specified

          -  No specific Child-Pugh Score will be required for eligibility.

          -  Patients with liver involvement with primary or metastatic cancer are eligible, if the
             patient also has a diagnosis from list in eligibility

          -  Platelet count of < 80,000/mcL at time of enrollment, and no platelet count ≥
             80,000/mcL in the 4 weeks prior to enrollment. A platelet count ≥ 80,000/mcL in the
             prior 4 weeks within 72 hours of a platelet transfusion will not make a patient
             ineligible.

          -  No prior cancer directed therapy that is cytotoxic, marrow suppressive, or has
             thrombocytopenia as a known common side effect in the past 12 months.

             a. For purposes of this study, cytotoxic/marrow suppressive systemic cancer therapy
             drugs will include: i. Nucleoside Analogue, including gemcitabine and fluorouracil ii.
             Carboplatin or cisplatin iii. Anthracycline iv. Alkylating agent v. Other cancer
             directive therapies with thrombocytopenia as a known common toxicity even if not
             cytotoxic b. If a patient has received cytotoxic systemic cancer therapy at any time
             in the past, then patients will be evaluated for myelodysplastic syndrome and leukemia
             prior to enrollment

          -  ECOG Performance status ≤ 2.

        Exclusion Criteria:

          -  History of immune causes of thrombocytopenia (ITP).

          -  Presence of leukemia or myelodysplastic syndrome.

          -  Known bone metastases sufficient to result in at least one site of cortical bone
             destruction, osteolytic lesions, or osteoblastic lesions, on radiologic imaging.

          -  Patients who have previously received thrombopoietin mimetics such as romiplostim,
             eltrombopag, etc.

          -  Patients who require emergent systemic cancer therapy will be excluded.

          -  Patients who require emergent radiation therapy will be excluded.

             a. Note: Concomitant radiation therapy with systemic cancer therapy is permitted.

          -  Pancytopenia at enrollment (Hemoglobin <9 g/dL and/or Absolute Neutrophil Count <
             1500/mcL).

             a. G-CSF and Red Blood Cell transfusions to treat anemia and neutropenia and achieve
             adequate hemoglobin and ANC are permitted.

          -  Patients with serum sodium ≤130 mEq/L will be excluded.

          -  Patients with a known bleeding disorder or platelet dysfunction will be excluded

               1. Baseline Prothrombin Time (PT) that is greater than 2" above the upper limit of
                  normal.

               2. Activated Partial Thromboplastin Time (aPTT) that is greater than 3" above the
                  upper limit of normal.

          -  Patients with known genetic prothrombotic conditions (Factor V Leiden, Prothrombin
             20210A, Antithrombin deficiency or Protein C or S deficiency) or history of
             antiphospholipid syndrome.

          -  Patients on anticoagulation or NSAIDs within 7 days of enrollment will be excluded,
             with the exception of celecoxib.

          -  Patients with concurrent lymphoma will be excluded.

          -  Patients will be excluded if they have a known pre-existing portal vein thrombus,
             mesenteric thrombus, or splenic thrombus that is not in the context of tumor invasion.
             Pre-existing tumor-associated portal vein thrombus, mesenteric thrombus, or splenic
             thrombus are not excluded.

          -  Potential drug interactions: Moderate or strong inducers of cytochrome p450 (CYP)2C9
             or CYP3A4/5 and use of dual moderate inhibitors of CYP2C9 and CYP3A4/5 may interact
             with Avatrombopag. Patients will be ineligible if they are receiving any of the
             following drugs:

               1. Itraconazole, Fluconazole, Rifampin, Cyclosporine, Verapamil

               2. If patients had been previously receiving the above drugs, the last dose must
                  have been administered 7 or more days before initiation of the first dose of
                  Avatrombopag.

          -  Females who are pregnant or breastfeeding or planning to become pregnant or breastfeed
             during treatment and for an additional 30 days after treatment discontinuation or
             longer if required by prescribing information for systemic cancer therapy received
             during the study will be excluded.

          -  Patients unwilling to use highly effective contraception during the study period and
             for the duration required by prescribing information for systemic cancer therapy (ies)
             administered during the study.

               1. If a woman, before entry she must be: postmenopausal (for at least 12 months), or
                  surgically sterile (have had a total hysterectomy or bilateral oophorectomy,
                  tubal ligation, or otherwise be incapable of pregnancy), or practicing a highly
                  effective method of birth control, if sexually active, including hormonal
                  prescription oral contraceptives,contraceptive injections, contraceptive patch,
                  intrauterine device, double-barrier method for less effective methods of
                  contraception (eg,condoms, diaphragm, cervical cap, or sponge with spermicidal
                  foam, cream, or gel), or male partner sterilization, consistent with local
                  regulations regarding use of birth control methods for subjects participating in
                  clinical trials, for the duration of their participation in the study, or not
                  heterosexually active.

                  Note: subjects who are not heterosexually active at screening must agree to
                  utilize a highly effective method of birth control if they become heterosexually
                  active during their participation in the study.

               2. If a man, must agree to use an adequate contraception method as deemed
                  appropriate by the investigator (eg, vasectomy, condoms, partner using effective
                  contraception).