Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

A Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of VT-464 in Patients With Advanced Breast Cancer

Protocol: OSU-15246

Full Title

A Phase I/II Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of VT-464 in Patients with Advanced Breast Cancer

Purpose

The goal of this clinical study is to determine the safety, tolerability, pharmacokinetics

and activity of VT-464, a lyase-selective inhibitor of CYP17, in patients with advanced

breast cancer.

Study Objective

This is a non-randomized, open-label, Phase 1/2 trial of VT-464 in patients with AR (+) TNBC

or ER (+)/HER2 normal unresectable locally advanced MBC. There will be a dose confirmation

Phase 1 portion of the study to establish the recommended Phase 2 dose. Phase 2 will be an

open-label, multi-center study and divided into parallel cohorts: AR (+) TNBC and ER (+) BC

patients at the RP2D confirmed/established in Phase 1.

Are you eligible?

Inclusion Criteria:

Inclusion Criteria:

1. Patients must have documented histological or cytological evidence of invasive cancer

of the breast. Measureable disease is not required.

2. Phase 1 patients must have TNBC or ER(+) HER2 normal breast cancer and Phase 2

patients must have AR(+) TNBC or ER(+) HER2 normal breast cancer

ER positive is defined as positive if ≥1% by IHC

ER/PgR(-) is defined as negative if 0% by IHC

HER2 normal is defined as IHC 0-1+ or IHC 2+(and FISH less than 2), or FISH less

than 2.0

AR(+) is defined as ≥1% by IHC. The assessment of AR expression may have been

performed any time in the past. Enrollment may be based on local pathology

findings with subsequent review of AR expression by central pathology to

determine if the patient will be considered evaluable for Phase 2. For patients

without known AR status in Phase 2, AR assessment will be performed as a

pre-screening test following the signing of a separate non-therapeutic informed

consent.

3. Female patients with ER(+)/HER2 normal tumors must be post-menopausal defined as

cessation of regular menses for at least 12 consecutive months with no alternative

pathological or physiological cause, and have a serum FSH level within the

laboratory's reference range for postmenopausal females that are ≥ 60 years old.

Ovarian suppression with a LHRH agonist or antagonists to achieve cessation of

regular menses is allowed on study. Male patients with ER(+)/HER2 normal tumors must

be undergoing gonadal suppression using LHRH agonists or antagonists prior to dosing

with VT-464 and continue with the LHRH agonist or antagonist for the duration of the

study.

4. Patients with ER(+)/HER2 normal tumors must have progression of disease following at

least 1 prior line of endocrine therapy. Progression of disease within 6 months of

adjuvant endocrine therapy will be considered a line of prior endocrine therapy.

Patients in the TNBC - Enzalutamide Treated Cohort (Cohort 2) must have received

prior enzalutamide for breast cancer.

5. Availability of a representative, formalin-fixed, paraffin-embedded, tumor specimen

that enables the definitive diagnosis of breast cancer with adequate viable tumor

cells in a tissue block (preferred) or ≥ 10 (20 preferred) freshly cut, unstained,

serial slides and the associated pathology report are required prior to enrollment

(All Phase 2 patients and Phase 1 patients to be considered part of the Phase 2

evaluable population).

6. Patients must ≥ 18 years of age

7. ECOG PS of 0 or 1

8. Patients must have adequate hematopoietic function as evidenced by:

WBC ≥ 3,000/μl

ANC ≥ 1,500/μl

Platelet count ≥ 100,000/μl

HGB ≥ 10 g/dl and not transfusion dependent

9. Patients must have adequate hepatic function as evidenced by:

AST/ALT levels ≤ 3X the ULN

Bilirubin levels of ≤ 2.0 mg/dl

10. Patients must have adequate renal function as evidenced by a serum creatinine of ≤

2.0 mg/dl.

11. Patients must have K+ >3.5 mEq/l.

12. Women of child-bearing potential must have a negative serum or urine pregnancy test

within 72 hours of Cycle 1 Day 1. Female patients who are not of childbearing

potential meet at least one of the following criteria:

Have undergone a documented hysterectomy and/or bilateral oophorectomy,

Have medically confirmed ovarian failure, or

Achieved post-menopausal status, defined as cessation of regular menses for at

least 12 consecutive months with no alternative pathological or physiological

cause, and have a serum FSH level within the laboratory's reference range for

postmenopausal females that are < 60 years old. Ovarian suppression with a LHRH

agonist to achieve cessation of regular menses is allowed on study.

13. Women of child-bearing potential and men who have partners of child-bearing potential

must agree to use two highly effective methods of contraception throughout the study

and for at least 30 days after the last dose of VT-464 for women and 90 days after

the last dose of VT-464 for men. Men must also agree to not donate sperm through 90

days following the last dose of VT-464. For men, one form must be a male condom.

Exclusion Criteria:

Inclusion Criteria:

1. Patients must have documented histological or cytological evidence of invasive cancer

of the breast. Measureable disease is not required.

2. Phase 1 patients must have TNBC or ER(+) HER2 normal breast cancer and Phase 2

patients must have AR(+) TNBC or ER(+) HER2 normal breast cancer

ER positive is defined as positive if ≥1% by IHC

ER/PgR(-) is defined as negative if 0% by IHC

HER2 normal is defined as IHC 0-1+ or IHC 2+(and FISH less than 2), or FISH less

than 2.0

AR(+) is defined as ≥1% by IHC. The assessment of AR expression may have been

performed any time in the past. Enrollment may be based on local pathology

findings with subsequent review of AR expression by central pathology to

determine if the patient will be considered evaluable for Phase 2. For patients

without known AR status in Phase 2, AR assessment will be performed as a

pre-screening test following the signing of a separate non-therapeutic informed

consent.

3. Female patients with ER(+)/HER2 normal tumors must be post-menopausal defined as

cessation of regular menses for at least 12 consecutive months with no alternative

pathological or physiological cause, and have a serum FSH level within the

laboratory's reference range for postmenopausal females that are ≥ 60 years old.

Ovarian suppression with a LHRH agonist or antagonists to achieve cessation of

regular menses is allowed on study. Male patients with ER(+)/HER2 normal tumors must

be undergoing gonadal suppression using LHRH agonists or antagonists prior to dosing

with VT-464 and continue with the LHRH agonist or antagonist for the duration of the

study.

4. Patients with ER(+)/HER2 normal tumors must have progression of disease following at

least 1 prior line of endocrine therapy. Progression of disease within 6 months of

adjuvant endocrine therapy will be considered a line of prior endocrine therapy.

Patients in the TNBC - Enzalutamide Treated Cohort (Cohort 2) must have received

prior enzalutamide for breast cancer.

5. Availability of a representative, formalin-fixed, paraffin-embedded, tumor specimen

that enables the definitive diagnosis of breast cancer with adequate viable tumor

cells in a tissue block (preferred) or ≥ 10 (20 preferred) freshly cut, unstained,

serial slides and the associated pathology report are required prior to enrollment

(All Phase 2 patients and Phase 1 patients to be considered part of the Phase 2

evaluable population).

6. Patients must ≥ 18 years of age

7. ECOG PS of 0 or 1

8. Patients must have adequate hematopoietic function as evidenced by:

WBC ≥ 3,000/μl

ANC ≥ 1,500/μl

Platelet count ≥ 100,000/μl

HGB ≥ 10 g/dl and not transfusion dependent

9. Patients must have adequate hepatic function as evidenced by:

AST/ALT levels ≤ 3X the ULN

Bilirubin levels of ≤ 2.0 mg/dl

10. Patients must have adequate renal function as evidenced by a serum creatinine of ≤

2.0 mg/dl.

11. Patients must have K+ >3.5 mEq/l.

12. Women of child-bearing potential must have a negative serum or urine pregnancy test

within 72 hours of Cycle 1 Day 1. Female patients who are not of childbearing

potential meet at least one of the following criteria:

Have undergone a documented hysterectomy and/or bilateral oophorectomy,

Have medically confirmed ovarian failure, or

Achieved post-menopausal status, defined as cessation of regular menses for at

least 12 consecutive months with no alternative pathological or physiological

cause, and have a serum FSH level within the laboratory's reference range for

postmenopausal females that are < 60 years old. Ovarian suppression with a LHRH

agonist to achieve cessation of regular menses is allowed on study.

13. Women of child-bearing potential and men who have partners of child-bearing potential

must agree to use two highly effective methods of contraception throughout the study

and for at least 30 days after the last dose of VT-464 for women and 90 days after

the last dose of VT-464 for men. Men must also agree to not donate sperm through 90

days following the last dose of VT-464. For men, one form must be a male condom.

Breast Cancer