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

NCT ID: NCT03775525

Last Updated: 2022-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

127 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-01

Study Completion Date

2023-12-31

Brief Summary

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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

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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.

Conditions

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Experimental: monotherapy

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

Group Type EXPERIMENTAL

GZ17-6.02

Intervention Type DRUG

Super enhancer Inhibition

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.

Group Type EXPERIMENTAL

GZ17-6.02

Intervention Type DRUG

Super enhancer Inhibition

Capecitabine

Intervention Type DRUG

antimetabolite

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.

Group Type EXPERIMENTAL

GZ17-6.02

Intervention Type DRUG

Super enhancer Inhibition

Capecitabine

Intervention Type DRUG

antimetabolite

Interventions

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GZ17-6.02

Super enhancer Inhibition

Intervention Type DRUG

Capecitabine

antimetabolite

Intervention Type DRUG

Other Intervention Names

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Xeloda

Eligibility Criteria

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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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Translational Drug Development

OTHER

Sponsor Role collaborator

Genzada Pharmaceuticals USA, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kathryn Gazarik

Role: STUDY_DIRECTOR

Translational Drug Development

Locations

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HonorHealth Research Institute

Scottsdale, Arizona, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 35276694 (View on PubMed)

Other Identifiers

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GEN-602-CT-101

Identifier Type: -

Identifier Source: org_study_id