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Study Evaluating GZ17-6.02 in Patients With Advanced Solid Tumors or in Combination With Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer (GEN602)

Primary Purpose

Advanced Cancer, Gastric Cancer, Breast Cancer

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GZ17-6.02
Capecitabine
Sponsored by
Genzada Pharmaceuticals USA, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • HonorHealth Research Institute
  • Cedars-Sinai Medical Center
  • Ochsner Clinic Foundation
  • Baylor Charles A. Sammons Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Experimental: monotherapy

Experimental: Combination with Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer

Experimental: Combination with Capecitabine in Metastatic Colorectal Cancer

Arm Description

GZ17-6.02 given orally on a daily x 28 day schedule. This will be a dose escalation study.

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.

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.

Outcomes

Primary Outcome Measures

maximum tolerated dose (MTD)
As assessed by CTCAE v4.03
Recommended dose of GZ17-6.02 for future phase II clinical studies
Dose-limiting toxicity

Secondary Outcome Measures

Antitumor effect
Area Under Concentration Curve
Maximum Plasma Concentration (Cmax)
Time to Maximum Plasma Concentration (Tmax)
Terminal Phase Half-Life (t1/2)
Total Body Clearance (CL/F)
Apparent Volume of Distribution (Vd/F)

Full Information

First Posted
December 6, 2018
Last Updated
December 22, 2022
Sponsor
Genzada Pharmaceuticals USA, Inc.
Collaborators
Translational Drug Development
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1. Study Identification

Unique Protocol Identification Number
NCT03775525
Brief Title
Study Evaluating GZ17-6.02 in Patients With Advanced Solid Tumors or in Combination With Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer
Acronym
GEN602
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 1, 2019 (Actual)
Primary Completion Date
May 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzada Pharmaceuticals USA, Inc.
Collaborators
Translational Drug Development

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Cancer, Gastric Cancer, Breast Cancer, Pancreatic Cancer, Prostate Cancer Metastatic, Colo-rectal Cancer, Solid Tumor, Solid Carcinoma, Solid Carcinoma of Stomach, Cancer of Stomach, Lymphoma, Sarcoma, Cutaneous T Cell Lymphoma, Head and Neck Squamous Cell Carcinoma, Basal Cell Carcinoma, Cutaneous T-cell Lymphoma, Cutaneous Squamous Cell Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
127 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental: monotherapy
Arm Type
Experimental
Arm Description
GZ17-6.02 given orally on a daily x 28 day schedule. This will be a dose escalation study.
Arm Title
Experimental: Combination with Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer
Arm Type
Experimental
Arm Description
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.
Arm Title
Experimental: Combination with Capecitabine in Metastatic Colorectal Cancer
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
GZ17-6.02
Intervention Description
Super enhancer Inhibition
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
antimetabolite
Primary Outcome Measure Information:
Title
maximum tolerated dose (MTD)
Description
As assessed by CTCAE v4.03
Time Frame
18 months
Title
Recommended dose of GZ17-6.02 for future phase II clinical studies
Time Frame
18 months
Title
Dose-limiting toxicity
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Antitumor effect
Time Frame
18 months
Title
Area Under Concentration Curve
Time Frame
18 months
Title
Maximum Plasma Concentration (Cmax)
Time Frame
18 months
Title
Time to Maximum Plasma Concentration (Tmax)
Time Frame
18 months
Title
Terminal Phase Half-Life (t1/2)
Time Frame
18 months
Title
Total Body Clearance (CL/F)
Time Frame
18 months
Title
Apparent Volume of Distribution (Vd/F)
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kathryn Gazarik
Organizational Affiliation
Translational Drug Development
Official's Role
Study Director
Facility Information:
Facility Name
HonorHealth Research Institute
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Ochsner Clinic Foundation
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Baylor Charles A. Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35276694
Citation
Booth L, West C, Von Hoff D, Dent P. Mechanisms of GZ17-6.02 resistance. Anticancer Drugs. 2022 Jun 1;33(5):415-423. doi: 10.1097/CAD.0000000000001203.
Results Reference
derived

Learn more about this trial

Study Evaluating GZ17-6.02 in Patients With Advanced Solid Tumors or in Combination With Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer

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