GEN602: Study Evaluating GZ17-6.02 in Patients With Advanced Solid Tumors or in Combination With Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer
Study Details
Study Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Experimental: monotherapy GZ17-6.02 given orally on a daily x 28 day schedule. This will be a dose escalation study. |
Drug: GZ17-6.02
Super enhancer Inhibition
|
| Experimental: Experimental: Combination with Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer GZ17-6.02 given orally twice daily x 21 day schedule in combination with Capecitabine 825 mg/m2 orally twice daily for 14 days x 21 day schedule. |
Drug: GZ17-6.02
Super enhancer Inhibition
Drug: Capecitabine
antimetabolite
Other Names:
|
| Experimental: Experimental: Combination with Capecitabine in Metastatic Colorectal Cancer GZ17-6.02 given orally twice daily x 21 day schedule in combination with Capecitabine 850 mg/m2 orally twice daily for 14 days x 21 day schedule. |
Drug: GZ17-6.02
Super enhancer Inhibition
Drug: Capecitabine
antimetabolite
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Antitumor effect [18 months]
- Area Under Concentration Curve [18 months]
- Maximum Plasma Concentration (Cmax) [18 months]
- Time to Maximum Plasma Concentration (Tmax) [18 months]
- Terminal Phase Half-Life (t1/2) [18 months]
- Total Body Clearance (CL/F) [18 months]
- Apparent Volume of Distribution (Vd/F) [18 months]
Eligibility Criteria
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
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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
-
Life expectancy of at least 3 months
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Age 18 years
-
Signed, written IRB-approved informed consent
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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:
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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
-
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
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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 methods during the study
-
Fasting glucose ≤ 180 mg/dL
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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;
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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);
-
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 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);
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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):
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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
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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;
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Known active, uncontrolled bacterial, viral, or fungal infections requiring systemic 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 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.
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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, 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;
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Unwillingness or inability to comply with procedures required in this protocol;
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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;
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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.
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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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Active CNS metastases requiring treatment or radiotherapy, or which have not been confirmed stable on radiographic imaging for ≥30 days prior to C1D1;
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Patients requiring steroids for neurological signs and symptom stabilization.
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Patients who are unable to successfully discontinue all prohibited medications listed in Appendix 6;
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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.
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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 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.
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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;
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | HonorHealth Research Institute | Scottsdale | Arizona | United States | 85258 |
| 2 | Cedars-Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 3 | Ochsner Clinic Foundation | New Orleans | Louisiana | United States | 70121 |
| 4 | Baylor Charles A. Sammons Cancer Center | Dallas | Texas | United States | 75246 |
Sponsors and Collaborators
- Genzada Pharmaceuticals USA, Inc.
- Translational Drug Development
Investigators
- Study Director: Kathryn Gazarik, Translational Drug Development
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GEN-602-CT-101