Avatrombopag for Thrombocytopenia in People With Cancer
Avatrombopag for Thrombocytopenia in People With Cancer
This study will test whether avatrombopag is an effective treatment for thrombocytopenia in
 people who have both cancer and a liver disease (such as cirrhosis, cholangitis, or
 hepatitis). Researchers will look at whether giving participants avatrombopag for 3 weeks can
 raise their platelet levels enough for them to begin chemotherapy. The study will also test
 whether avatrombopag can continue to be effective against thrombocytopenia while participants
 are on chemotherapy for 12 weeks or longer. In addition, researchers will determine how safe
 the study drug is in participants.
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).