Avatrombopag vs. Placebo for CIT in GI Malignancies

Inclusion Criteria: * A diagnosis of persistent chemotherapy-induced thrombocytopenia, as defined by a platelet count of \<85,000/µL on Day 1 of a chemotherapy cycle. * Age ≥18 years at the time of informed consent. Because no dosing or adverse event data are currently available on the use of avatrombopag for CIT in participants \<18 years of age, children are excluded from this study, but may be eligible for future pediatric trials. * Receiving cytotoxic chemotherapy for a gastrointestinal malignancy, including esophageal, gastric, small bowel, hepatobiliary (cholangiocarcinoma, gallbladder carcinoma, hepatocellular carcinoma), pancreatic, or colorectal cancer. Lymphomas are not eligible. Patients of any stage are eligible. * The chemotherapy regimen being used to treat the patient's gastrointestinal malignancy must be administered in 14, 21, or 28-day cycles and include at least one of the following agents: fluorouracil, capecitabine, floxuridine, trifluridine/tipiracil, gemcitabine, cisplatin, carboplatin, oxaliplatin, irinotecan, liposomal irinotecan, paclitaxel, nanoalbumin-bound paclitaxel, docetaxel, epirubicin, or doxorubicin. * A plan to continue the current chemotherapy regimen (the regimen that resulted in CIT) at the same dose and schedule for at least 1 more cycle if the platelet count is adequate (\>100,000/µL). * Participant has not received cytotoxic chemotherapy in the 13 days before study Day 1, except for infusional fluorouracil in regimens with a 14-day cycle length or oral cytotoxic chemotherapy agents. . * Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (see Appendix B) and a life expectancy of \>12 weeks at screening. * Participants must have adequate organ and marrow function as defined below. Use of standard-of-care G-CSF and/or red cell transfusions to achieve adequate ANC and hemoglobin levels is allowed. * Absolute neutrophil count (ANC) ≥500/µL * Hemoglobin ≥8 g/dL * AST (SGOT) and ALT (SGPT) ≤5 × institutional ULN * Total bilirubin ≤3 × institutional ULN * The effects of avatrombopag on the developing human fetus are unknown. For this reason, women of child-bearing potential and men (except for a vasectomized man with confirmed azoospermia) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for the 30 days after discontinuation of study drug. 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. * Participant is willing and able to comply with the study protocol. * Ability to understand and the willingness to sign a written informed consent document, unless the participant lacks capacity to provide consent, in which case a legally authorized representative (LAR) gives permission for the participant to participate. Exclusion Criteria: * Participant has a history of hematologic malignancy, including leukemia, lymphoma, myeloma, myelodysplastic syndrome, or a myeloproliferative neoplasm, with the exception of a non-clinically significant neoplasm in the judgement of the investigator (e.g., indolent B-cell neoplasm not requiring treatment, monoclonal gammopathy of undetermined significance, etc.). * Participant has known bone marrow invasion by tumor or multiple (greater than 1) bony metastatic lesions. Participants do not need to undergo screening with bone marrow biopsy or imaging to satisfy this criterion. * Participant has received prior irradiation directly to the pelvic bones of a dose of \>20 Gy. * Participants with a history of a prior major venous thromboembolic event, such as a deep vein thrombosis or pulmonary embolism, or symptomatic arterial thrombotic events such as a myocardial infarction, ischemic cerebral vascular accident or transient ischemic attack will be ineligible if they have not tolerated anticoagulation therapy. If patients remain on anticoagulation or have completed the prescribed course of anticoagulation, they will be eligible for enrollment. A venous thrombotic event associated with a central venous catheter or a superficial venous thrombosis will not make the patient ineligible. * Participant has spontaneous recovery of the platelet count to \>100,000/µL prior to randomization. * Participant has any known clinically significant acute or active bleeding (e.g. gastrointestinal or central nervous system) within 7 days prior to consent. * Participants who are receiving any other investigational agents or have received any other investigational agent within 30 days of study Day 1. * History of hypersensitivity reactions to avatrombopag or any of its excipients. * Participants with uncontrolled intercurrent illness, in the opinion of the investigator. * Participants with psychiatric illness/social situations that would limit compliance with study requirements, in the opinion of the investigator. * Pregnant women are excluded from this study because the effect of avatrombopag on the developing fetus are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with avatrombopag, breastfeeding should be discontinued if the mother is treated with avatrombopag. Pregnancy status will be assessed with a serum B-HCG pregnancy test in women of child-bearing potential (see Section 10 for timing). Women who are menopausal or perimenopausal will have follicle-stimulating hormone levels drawn to confirm menopausal status. * Participant has received a platelet transfusion within 3 days of study Day 1. * Participant is unable to take oral medication. * Participant has received a thrombopoietin receptor agonist (romiplostim, eltrombopag, avatrombopag, or lusutrombopag) for any reason within 14 days of study Day 1. * Participant has a history of active chronic platelet disorders or thrombocytopenia due to an etiology other than CIT, in the opinion of the investigator. * Any other medical condition or factor that, in the opinion of the investigator, is likely to interfere with completion of the study.