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Patients with a pathologically confirmed diagnosis of advanced solid tumors or lymphoma |
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Tumor progression after receiving standard/approved therapies which may include chemotherapy, targeted agents, radio-immuno conjugates, check point inhibitors, where there is no approved therapy; or the patient is intolerant of standard of care or the patient declines standard of care treatment |
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One or more metastatic tumors measurable, or evaluable, per RECIST v1.1 Criteria for solid tumors and Lugano Criteria for lymphoma |
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Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 |
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Life expectancy of at least 3 months |
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Age 18 years |
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Signed, written IRB-approved informed consent |
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A negative pregnancy test (if female) |
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Acceptable liver function |
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Bilirubin ≤ 1.5 times upper limit of normal |
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AST (SGOT), ALT (SGPT) and Alkaline phosphatase ≤ 2.5 times upper limit of normal (if liver metastases are present, then ≤ 5 x ULN is allowed) |
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Acceptable renal function |
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Serum creatinine ≤ 1.5 times institutional ULN, OR calculated creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal |
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Acceptable hematologic status |
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Granulocyte ≥ 1500 cells/mm3 |
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Platelet count ≥ 100,000 (plt/mm3) |
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Hemoglobin ≥ 9 g/dL |
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Urinalysis |
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No clinically significant abnormalities |
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Acceptable coagulation status (for patients on warfarin or other anti-coagulants, a |
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PT/PTT considered by the PI as therapeutically appropriate will be allowed) |
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PT within ≤ 1.5 times normal limits |
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PTT within ≤ 1.5 times normal limits |
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For men and women of child-producing potential, the use of effective contraceptive |
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methods during the study |
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Fasting glucose ≤ 180 mg/dL |
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Albumin ≥ 3.0 g/dL within seven days of initiating protocol treatment |
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For patients in the GZ17-6.02 plus capecitabine Phase 1b Expansion Cohort 2 (metastatic |
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breast cancer) |
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Pathologically confirmed diagnosis of HER2-negative and Hormone Receptor (HR) |
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(estrogen receptor [ER] and/or progesterone receptor)-positive metastatic breast |
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cancer |
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Had ≤ 1 prior treatment (not including neoadjuvant or adjuvant treatment) |
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Are naïve to capecitabine but not necessarily to fluorouracil (5 FU) |
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Eligible for standard-of-care treatment with capecitabine monotherapy |
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Patients in Expansion Cohort 2 with bone-only metastatic disease must have one or more |
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lytic or a mixed lytic-blastic lesions that can be assessed by computed tomography |
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(CT) scan or magnetic resonance imaging (MRI) |
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For patients in GZ17-6.02 plus capecitabine Phase 1b Expansion Cohort 3 (metastatic |
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colorectal cancer) |
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Pathologically confirmed diagnosis of metastatic colorectal cancer |
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Had ≤ 2 prior treatments (not including neoadjuvant or adjuvant treatment) |
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Are naïve to capecitabine but not necessarily to 5 FU |
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Eligible for standard-of-care treatment with capecitabine monotherapy |
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Currently taking MAOIs
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Unwillingness or inability to comply with procedures required in this protocol
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Patients who are currently receiving any other investigational agent
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Primary Central Nervous System (CNS) malignancies
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Patients requiring steroids for neurological signs and symptom stabilization
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(All patients, unless otherwise specified)
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New York Heart Association Class III or IV, cardiac disease, myocardial infarction
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within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG
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Baseline QTc exceeding 450 msec in males, 470 msec in females (using the Fridericia's
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formula) and/or patients receiving class 1A or class III antiarrhythmic agents
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Known active, uncontrolled bacterial, viral, or fungal infections requiring systemic
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therapy
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Pregnant or nursing women
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NOTE: Women of child-bearing potential and men must agree to use adequate
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contraception (hormonal or barrier method of birth control; or abstinence) prior to
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study entry and for the duration of study participation. Should a woman become
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pregnant or suspect she is pregnant while participating in this study, she should
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inform her treating physician immediately
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Treatment with radiation therapy or surgery within 1 month prior to study entry
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Treatment with chemotherapy, targeted therapeutics (e.g. tyrosine kinase inhibitors
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therapeutic antibodies, etc), or investigational therapies within 1 month, or 5
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half-lives (whichever is shorter), prior to study entry (6 weeks for nitrosoureas or
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mitomycin C). For radiopharmaceuticals, within 1 month unless hematopoietic recovery
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has not returned to pretreatment baseline
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Known active infection with HIV, HTLV-1, hepatitis B, hepatitis C or other chronic
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viral infections that could interfere with the interpretation of study data
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Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other
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conditions) that could compromise protocol objectives in the opinion of the
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investigator and/or the sponsor
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Active CNS metastases requiring treatment or radiotherapy, or which have not been
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confirmed stable on radiographic imaging for ≥30 days prior to C1D1
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Patients who are unable to successfully discontinue all prohibited medications listed
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in Appendix 6
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Patients must not have received a transfusion (platelets or red blood cells) ≤ 2 weeks
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prior to initiating protocol therapy
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For patients in the GZ17-6.02 monotherapy Dose Escalation Cohort and patients in Expansion
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Cohort 1
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• Patients with cow's milk allergy or with galactosemia
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Phase 1b Expansion Cohort 2 (metastatic breast cancer) and Expansion Cohort 3 (metastatic
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colorectal cancer)
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Any history of coronary artery disease is exclusionary; New York Heart Association
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Class III or IV, cardiac disease, myocardial infarction within the past 6 months
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unstable arrhythmia, or evidence of ischemia on the ECG
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Any conditions or medications that are contraindicated with capecitabine dosing
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Dihydropyrimidine dehydrogenase (DPD) deficiency
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Known sensitivity to capecitabine or any of its components or to 5-FU
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Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other
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conditions) that could compromise protocol objectives in the opinion of the
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investigator and/or the sponsor
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o This includes prior gastrointestinal surgery that would interfere with the oral drug
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absorption
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Malignancy other than metastatic breast cancer (Expansion Cohort 2) or metastatic
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colorectal cancer (Expansion Cohort 3) that required therapy within the preceding 5
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years, other than adequately treated
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non-melanoma skin cancer or in situ cancer
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another cancer that has a very low risk of interfering with the safety or
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efficacy endpoints of the study, must be approved by the Sponsor medical team
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