- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03775525
Study Evaluating GZ17-6.02 in Patients With Advanced Solid Tumors or in Combination With Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer (GEN602)
A Phase I/Ib, 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
Study Overview
Status
Conditions
- Sarcoma
- Lymphoma
- Breast Cancer
- Gastric Cancer
- Pancreatic Cancer
- Solid Tumor
- Cutaneous T-cell Lymphoma
- Advanced Cancer
- Head and Neck Squamous Cell Carcinoma
- Colo-rectal Cancer
- Cutaneous T Cell Lymphoma
- Prostate Cancer Metastatic
- Basal Cell Carcinoma
- Solid Carcinoma
- Solid Carcinoma of Stomach
- Cancer of Stomach
- Cutaneous Squamous Cell Carcinoma
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
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Arizona
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Scottsdale, Arizona, United States, 85258
- HonorHealth Research Institute
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California
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Los Angeles, California, United States, 90048
- Cedars-Sinai Medical Center
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Louisiana
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New Orleans, Louisiana, United States, 70121
- Ochsner Clinic Foundation
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Texas
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Dallas, Texas, United States, 75246
- Baylor Charles A. Sammons Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
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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.
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Super enhancer Inhibition
antimetabolite
Other Names:
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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.
|
Super enhancer Inhibition
antimetabolite
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
maximum tolerated dose (MTD)
Time Frame: 18 months
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As assessed by CTCAE v4.03
|
18 months
|
Recommended dose of GZ17-6.02 for future phase II clinical studies
Time Frame: 18 months
|
18 months
|
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Dose-limiting toxicity
Time Frame: 18 months
|
18 months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Antitumor effect
Time Frame: 18 months
|
18 months
|
Area Under Concentration Curve
Time Frame: 18 months
|
18 months
|
Maximum Plasma Concentration (Cmax)
Time Frame: 18 months
|
18 months
|
Time to Maximum Plasma Concentration (Tmax)
Time Frame: 18 months
|
18 months
|
Terminal Phase Half-Life (t1/2)
Time Frame: 18 months
|
18 months
|
Total Body Clearance (CL/F)
Time Frame: 18 months
|
18 months
|
Apparent Volume of Distribution (Vd/F)
Time Frame: 18 months
|
18 months
|
Collaborators and Investigators
Collaborators
Investigators
- Study Director: Kathryn Gazarik, Translational Drug Development
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Skin Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Stomach Diseases
- Breast Diseases
- Head and Neck Neoplasms
- Neoplasms, Squamous Cell
- Neoplasms, Basal Cell
- Lymphoma
- Stomach Neoplasms
- Breast Neoplasms
- Carcinoma
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Lymphoma, T-Cell
- Lymphoma, T-Cell, Peripheral
- Lymphoma, T-Cell, Cutaneous
- Carcinoma, Basal Cell
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Capecitabine
Other Study ID Numbers
- GEN-602-CT-101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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