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