Advanced Cancer, Basal Cell Carcinoma, Breast Cancer, Cancer of Stomach, Colo-rectal Cancer, Cutaneous Squamous Cell Carcinoma, Cutaneous T-cell Lymphoma, Cutaneous T Cell Lymphoma, Gastric Cancer, Head and Neck Squamous Cell Carcinoma, Lymphoma, Pancreatic Cancer, Prostate Cancer Metastatic, Sarcoma, Solid Carcinoma, Solid Carcinoma of Stomach, Solid Tumor
Conditions
Brief summary
This Phase I/Ib study is a Multicenter, Open-label, Dose-Escalation, Safety, Pharmacodynamic and Pharmacokinetic Study of GZ17-6.02 Monotherapy and in Combination with Capecitabine, Given Orally on a Daily Schedule in Patients with Advanced Solid Tumors or Lymphoma
Detailed description
This study will evaluate the safety, pharmacokinetics, and pharmacodynamic effects of a novel anti-cancer drug, GZ17-6.02 administered to patients with advanced solid tumors or lymphoma, which have progressed after receiving standard/approved therapy or where there is no approved therapy. This study will determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of GZ17-6.02 monotherapy and in combination with standard-of-care oncology treatments and to establish the dose of GZ17-6.02 recommended for future monotherapy and combination therapies phase II oncology clinical studies.
Interventions
DRUGGZ17-6.02
Super enhancer Inhibition
DRUGCapecitabine
antimetabolite
Sponsors
Translational Drug Development
Genzada Pharmaceuticals USA, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| maximum tolerated dose (MTD) | 18 months | As assessed by CTCAE v4.03 |
| Recommended dose of GZ17-6.02 for future phase II clinical studies | 18 months | — |
| Dose-limiting toxicity | 18 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to Maximum Plasma Concentration (Tmax) | 18 months |
| Terminal Phase Half-Life (t1/2) | 18 months |
| Antitumor effect | 18 months |
| Apparent Volume of Distribution (Vd/F) | 18 months |
| Total Body Clearance (CL/F) | 18 months |
| Area Under Concentration Curve | 18 months |
| Maximum Plasma Concentration (Cmax) | 18 months |
Countries
United States
Outcome results
None listed