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A Study of GDC-0810 Single Agent or in Combination With Palbociclib and/or a Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

Primary Purpose

Breast Cancer

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

GDC-0810

LHRH Agonist

Palbociclib

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

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

Inclusion Criteria:

Phase 1a portion

Histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of either locally recurrent disease not amenable to resection or radiation therapy with curative intent, or metastatic disease, both progressing after at least 6 months of hormonal therapy for estrogen receptor (ER) positive breast cancer
ER-positive, human epidermal growth factor 2 (HER2) negative
At least 2 months must have elapsed from the use of tamoxifen
At least 6 months must have elapsed from the use of fulvestrant
At least 2 weeks must have elapsed from the use of any other anticancer hormonal therapy
At least 3 weeks must have elapsed from the use of any chemotherapy
Postmenopausal status
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
Adequate organ function

Phase Ib portion

All above inclusion criteria, except:
Postmenopausal status, pre- and peri-menopausal participants will also be included
ECOG performance status less than 2
At least 2 months must have elapsed from the use of tamoxifen not applicable
At least 6 months must have elapsed from the use of fulvestrant not applicable

and plus:

Documented sensitivity to prior hormonal therapy
Cohort C1 (palbociclib combination cohorts): no prior treatment with cyclin-dependent kinase (CDK) 4/6 inhibitor

Phase IIa portion

All above inclusion criteria for Phase Ia, except:
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
At least 6 months must have elapsed from the use of fulvestrant not applicable

and plus:

Cohort A only: confirmed estrogen receptor alpha (ESR1) mutation and presence of measurable disease as per RECIST v1.1 or evaluable bone disease
Cohort A1 only: no prior fulvestrant allowed; at least 2 months must have elapsed from the use of tamoxifen
Cohort A2 only: prior fulvestrant allowed
Cohort B only: disease progression following no more than 1 prior treatment with an aromatase inhibitor in the advanced/metastatic setting
Cohort B1 only: no prior fulvestrant allowed
Cohort B2 only: prior fulvestrant allowed

Exclusion Criteria:

Phase 1a portion

Untreated or symptomatic central nervous system (CNS) metastases
Endometrial disorders
More than 2 prior chemotherapy in the advanced/metastatic setting (prior adjuvant chemotherapy is allowed so long as it occurred greater than or equal to 12 months prior to enrollment)
Current treatment with any systemic anticancer therapies for advanced disease
Any significant cardiac dysfunction within 12 months prior to enrollment
Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or upper gastrointestinal surgery including gastric resection
Known human immunodeficiency virus (HIV) infection
Known clinically significant history of liver disease
Major surgery within 4 weeks prior to enrollment
Radiation therapy within 2 weeks prior to enrollment

Phase Ib portion - all above exclusion criteria, plus:

Cohort C1 (palbociclib combination cohorts): history of venous thromboembolic event requiring therapeutic anticoagulation; vaginal bleeding within 2 months prior to enrollment

Phase IIa portion - all above exclusion criteria, plus:

Cohort A1, A2, and Cohort B2 only: more than 1 prior chemotherapy in the advanced/metastatic setting
Cohort B1 only: prior chemotherapy in the advanced/metastatic setting

Sites / Locations

Ucsd Medical Center
Massachusetts General Hospital.
Dana Farber Cancer Institute
Washington University
Mount SInai Medical Center
Memorial Sloan Kettering Cancer Center
Vanderbilt University Medical Center
Seattle Cancer Care Alliance
Seoul National University Hospital
Severance Hospital, Yonsei University Health System
VU MEDISCH CENTRUM; Dept. of Medical Oncology
Hospital Universitari Vall d'Hebron
Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
Hospital Clinico Universitario de Valencia

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm Type

Experimental

Arm Label

Phase Ia - Cohort 1

Phase Ia - Cohort 2

Phase Ia - Cohort 3

Phase Ia - Cohort 4

Phase Ia - Cohort 5

Phase Ia - Cohort 6

Phase Ia - Cohort 7

Phase Ia - Cohort 8

Phase Ia - Cohort 9

Phase IIa - Cohort A1

Phase IIa - Cohort A2

Phase IIa - Cohort B1

Phase IIa - Cohort B2

Phase Ib - Cohort C1

Phase Ib - Cohort D1

Arm Description

100 mg GDC-0810 once daily (QD) in fasting state.

200 mg GDC-0810 QD in fasting state.

400 mg GDC-0810 QD in fasting state.

600 mg GDC-0810 QD in fasting state.

600 mg GDC-0810 QD in non-fasting state.

300 mg GDC-0810 twice daily (BID) in fasting state.

800 mg GDC-0810 QD in fasting state.

800 mg GDC-0810 QD in non-fasting state.

400 mg GDC-0810 BID in fasting state.

600 mg GDC-0810 QD. Additionally, participants in this arm did not receive any prior treatment with fulvestrant and had confirmed ER-a (ESR1) mutation of the ligand binding domain (LBD).

600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and confirmed ER-a (ESR1) mutation of the LBD.

600 mg GDC-0810 QD. Additionally, participants in this arm did not receive any prior treatment with fulvestrant and had progressed following ≤1 prior therapy with an aromatase inhibitor (AI).

600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and progressed following ≤1 prior therapy with an AI.

400 mg GDC-0810 + 125 mg Palbociclib QD.

≤600 mg GDC-0810 QD + LHRH agonist once monthly.

Outcomes

Primary Outcome Measures

Phase Ia: Maximum Tolerated Dose of GDC-0810 When Used as a Single Agent

Maximum Tolerated Dose (MTD) is determined based on the number of Dose Limiting Toxicities (DLTs) experienced by the participants. DLTs were defined as any of the following adverse events (AEs) that are deemed by the investigator or the Sponsor to be related to study drug (toxicities will be attributed to single agent GDC-0810 unless they are clearly related to disease progression or can clearly be attributed to a cause other than GDC-0810 administration): Any grade ≥ 3 non-hematologic toxicity (excluding alopecia) Any grade ≥ 3 hematologic toxicity of > 7 days' duration Any grade toxicity that leads to study drug interruption of > 7 days' duration

Phase Ia: RP2D of GDC-0810 When Used as a Single Agent

The recommended Phase II dose (RP2D) was based on the overall safety/tolerability and pharmacokinetic profile of GDC-0810.

Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1

Objective response (OR) is defined as a complete response (CR) or partial response (PR) as determined by investigator assessment according to RECIST v1.1. OR was based on criteria related to changes in size of target lesions. CR was the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Phase IIa: Percentage of Participants With Clinical Benefit Response of GDC-0810 According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Clinical Benefit Response (CBR) is defined as the percentage of participants achieving confirmed RECIST v1.1 defined CR, PR, and/or stable disease. CR was the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Stable disease was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.

Phase Ib: RP2D of GDC-0810 When Used in Combination With Palbociclib and/or LHRH

The RP2D of GDC-0810 When Used in Combination With Palbociclib and/or LHRH RP2D was not determined since the development of the GDC-0810 was discontinued before enrolling Cohort C2. The RP2D would have been based on the overall safety and PK/PD profile of GDC-0810 and palbociclib, and not necessarily the MTD.

Secondary Outcome Measures

All Phases: Percentage of Participants With Adverse Events (AEs)

An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.

Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Maximum Plasma Concentration (Cmax) has been calculated using PK samples collected after administration of a single dose (on Day -7) and also following once-daily multiple doses (at steady state on Day 29) of GDC-0810.

Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Time to Maximum Concentration (Tmax) has been calculated using PK samples collected after administration of a single dose (on Day -7) and also following once-daily multiple doses (at steady state on Day 29) of GDC-0810.

Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Area under the concentration-time curves from time 0 to 6 hours (AUC0-6) has been calculated using PK samples collected after administration of a single dose (on Day -7) and also following once-daily multiple doses (at steady state on Day 29) of GDC-0810.

Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Area under the concentration-time curves from time 0 to 24 hours (AUC0-24) has been calculated using PK samples collected after administration of a single dose (on Day -7) and also following once-daily multiple doses (at steady state on Day 29) of GDC-0810.

Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf)

Area under the concentration-time curve from time 0-infinity (AUC0-inf) has been calculated using PK samples collected after administration of a single dose (on Day -7) of GDC-0810.

Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent

Half-life (t1/2) was calculated after single dose administration and not at steady state.

Phase Ia: Apparent Clearance (Cl/F)

Apparent Clearance (CL/F) was estimated using PK samples collected following administration of a single dose (on Day -7) of GDC-0810

Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula

The corrected QT interval (QTc) was calculated using Fridericia's formula from electrocardiogram (ECG) data. Changes in ECG intervals from baseline were calculated. Triplicate ECG measurements were collected throughout the study. The averaged triplicate ECG measurements were used for analysis.

Phase Ib: Cmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Cmax has been calculated using PK samples collected after GDC-0810 administration.

Phase Ib: Tmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Tmax has been calculated using PK samples collected after GDC-0810 administration.

Phase Ib: AUC0-6 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

AUC0-6 has been calculated using PK samples collected after GDC-0810 administration.

Phase Ib: t/2 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Half-life (t1/2) can be estimated only when the PK sample collection following a dose is long enough to characterize the elimination phase. The PK samples in these cohorts were only collected up to 6 hours following the dose, hence, t1/2 could not be estimated.

Phase Ib: Cmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Cmax has been calculated using PK samples collected after GDC-0810 administration.

Phase Ib: Tmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Tmax has been calculated using PK samples collected after GDC-0810 administration.

Phase Ib: AUC0-6 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

AUC0-6 has been calculated using PK samples collected after GDC-0810 administration.

Phase Ib: t/2 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Phase Ib: Cmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Cmax has been calculated using PK samples collected after GDC-0810 administration.

Phase Ib: Tmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Tmax has been calculated using PK samples collected after GDC-0810 administration.

Phase Ib: AUC0-6 of LHRH Agonist in Combination With GDC-0810 and/or an Palbociclib

AUC0-6 has been calculated using PK samples collected after GDC-0810 administration.

Phase Ib: t/2 of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Full Information

NCT ID

NCT01823835

First Posted

March 25, 2013

Last Updated

May 25, 2021

Sponsor

Genentech, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01823835

Brief Title

A Study of GDC-0810 Single Agent or in Combination With Palbociclib and/or a Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

Official Title

An Open-Label, Phase Ia/Ib/IIa Study of GDC-0810 Single Agent or in Combination With Palbociclib and/or an LHRH Agonist in Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Terminated

Why Stopped

The Sponsor decided to halt the development of GDC-0810, but not due to any safety concerns.

Study Start Date

December 29, 2014 (Actual)

Primary Completion Date

March 13, 2020 (Actual)

Study Completion Date

March 13, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Genentech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This study is a multi-institution, Phase Ia/Ib/IIa open-label, dose-finding, safety, pharmacokinetics (PK), and proof-of-concept study of GDC-0810 as a single agent and in combination with palbociclib and/or LHRH agonist. The study is divided into 3 phases: Phase Ia, Phase Ib, and Phase IIa. During Phase Ia (dose escalation phase), GDC-0810 single agent will be administered orally on a continuous daily dosing regimen with a Day -7 lead-in period for single dose PK evaluation prior to the start of daily treatment. The incidence of dose-limiting toxicities (DLTs) will be evaluated from Day -7 through the first cycle (28 days) of treatment (35 days total). Depending on safety and tolerability, participants will be assigned sequentially to escalating doses of GDC-0810 using standard 3 + 3 design. During Phase Ib (dose escalation and expansion phase), participants will receive GDC-0810 with palbociclib and/or LHRH agonist to determine the recommended Phase II dose (RP2D) and assess the safety and tolerability of concomitant administration. During Phase IIa (dose expansion phase), participants previously treated with an aromatase inhibitor (AI) will be treated at the RP2D to further characterize the safety, PK, pharmacodynamics, and anti-tumor activity of GDC-0810.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

152 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase Ia - Cohort 1

Arm Type

Experimental

Arm Description

100 mg GDC-0810 once daily (QD) in fasting state.

Arm Title

Phase Ia - Cohort 2

Arm Type

Experimental

Arm Description

200 mg GDC-0810 QD in fasting state.

Arm Title

Phase Ia - Cohort 3

Arm Type

Experimental

Arm Description

400 mg GDC-0810 QD in fasting state.

Arm Title

Phase Ia - Cohort 4

Arm Type

Experimental

Arm Description

600 mg GDC-0810 QD in fasting state.

Arm Title

Phase Ia - Cohort 5

Arm Type

Experimental

Arm Description

600 mg GDC-0810 QD in non-fasting state.

Arm Title

Phase Ia - Cohort 6

Arm Type

Experimental

Arm Description

300 mg GDC-0810 twice daily (BID) in fasting state.

Arm Title

Phase Ia - Cohort 7

Arm Type

Experimental

Arm Description

800 mg GDC-0810 QD in fasting state.

Arm Title

Phase Ia - Cohort 8

Arm Type

Experimental

Arm Description

800 mg GDC-0810 QD in non-fasting state.

Arm Title

Phase Ia - Cohort 9

Arm Type

Experimental

Arm Description

400 mg GDC-0810 BID in fasting state.

Arm Title

Phase IIa - Cohort A1

Arm Type

Experimental

Arm Description

600 mg GDC-0810 QD. Additionally, participants in this arm did not receive any prior treatment with fulvestrant and had confirmed ER-a (ESR1) mutation of the ligand binding domain (LBD).

Arm Title

Phase IIa - Cohort A2

Arm Type

Experimental

Arm Description

600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and confirmed ER-a (ESR1) mutation of the LBD.

Arm Title

Phase IIa - Cohort B1

Arm Type

Experimental

Arm Description

600 mg GDC-0810 QD. Additionally, participants in this arm did not receive any prior treatment with fulvestrant and had progressed following ≤1 prior therapy with an aromatase inhibitor (AI).

Arm Title

Phase IIa - Cohort B2

Arm Type

Experimental

Arm Description

600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and progressed following ≤1 prior therapy with an AI.

Arm Title

Phase Ib - Cohort C1

Arm Type

Experimental

Arm Description

400 mg GDC-0810 + 125 mg Palbociclib QD.

Arm Title

Phase Ib - Cohort D1

Arm Type

Experimental

Arm Description

≤600 mg GDC-0810 QD + LHRH agonist once monthly.

Intervention Type

Drug

Intervention Name(s)

GDC-0810

Intervention Description

GDC-0810 administered orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, GDC-0810 drug supply exhausted, or study termination (up to 3 years).

Intervention Type

Drug

Intervention Name(s)

LHRH Agonist

Intervention Description

LHRH agonist administered once monthly until disease progression, unacceptable toxicity, withdrawal of consent, GDC-0810 drug supply exhausted, or study termination (up to 3 years). Choice of LHRH agonist will be an institutional choice approved for use in breast cancer.

Intervention Type

Drug

Intervention Name(s)

Palbociclib

Intervention Description

Palbociclib administered orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, GDC-0810 drug supply exhausted, or study termination (up to 3 years).

Primary Outcome Measure Information:

Title

Phase Ia: Maximum Tolerated Dose of GDC-0810 When Used as a Single Agent

Description

Time Frame

Day -7 through the first cycle (28 days) of treatment (35 days total)

Title

Phase Ia: RP2D of GDC-0810 When Used as a Single Agent

Description

The recommended Phase II dose (RP2D) was based on the overall safety/tolerability and pharmacokinetic profile of GDC-0810.

Time Frame

Day -7 through the first cycle (28 days) of treatment (35 days total)

Title

Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1

Description

Time Frame

Screening and every 8 weeks from Cycle 1 Day 1 until Cycle 12, thereafter every 3 months until disease progression (up to 3 years)

Title

Phase IIa: Percentage of Participants With Clinical Benefit Response of GDC-0810 According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Description

Time Frame

Screening and every 8 weeks from Cycle 1 Day 1 until Cycle 12, thereafter every 3 months until disease progression (up to 3 years)

Title

Phase Ib: RP2D of GDC-0810 When Used in Combination With Palbociclib and/or LHRH

Description

Time Frame

first cycle (Days 1 to 28 of a 28-day schedule)

Secondary Outcome Measure Information:

Title

All Phases: Percentage of Participants With Adverse Events (AEs)

Description

Time Frame

up to 3 years

Title

Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Description

Time Frame

Single Dose: Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose; Multiple Doses: Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, hours postdose

Title

Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Description

Time Frame

Single Dose: Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose; Multiple Doses: Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, hours postdose

Title

Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Description

Time Frame

Single Dose: Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6 hours postdose; Multiple Doses: Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6 hours postdose

Title

Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Description

Time Frame

Single Dose: Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours postdose; Multiple Doses: Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours postdose

Title

Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf)

Description

Area under the concentration-time curve from time 0-infinity (AUC0-inf) has been calculated using PK samples collected after administration of a single dose (on Day -7) of GDC-0810.

Time Frame

Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours postdose

Title

Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent

Description

Half-life (t1/2) was calculated after single dose administration and not at steady state.

Time Frame

Day -7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose

Title

Phase Ia: Apparent Clearance (Cl/F)

Description

Apparent Clearance (CL/F) was estimated using PK samples collected following administration of a single dose (on Day -7) of GDC-0810

Time Frame

Day -7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose

Title

Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula

Description

Time Frame

Screening; on Cycle 2 Day 1 predose and at 1, 2, 3, 4, and 6 hours postdose; Cycle 3 Day 1 predose, and at 1, 3, and 6 hours post dose

Title

Phase Ib: Cmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Description

Cmax has been calculated using PK samples collected after GDC-0810 administration.

Time Frame

C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8; D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Title

Phase Ib: Tmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Description

Tmax has been calculated using PK samples collected after GDC-0810 administration.

Time Frame

C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8; D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Title

Phase Ib: AUC0-6 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Description

AUC0-6 has been calculated using PK samples collected after GDC-0810 administration.

Time Frame

C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8; D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Title

Phase Ib: t/2 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Description

Time Frame

C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8; D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Title

Phase Ib: Cmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Description

Cmax has been calculated using PK samples collected after GDC-0810 administration.

Time Frame

Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8

Title

Phase Ib: Tmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Description

Tmax has been calculated using PK samples collected after GDC-0810 administration.

Time Frame

Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8

Title

Phase Ib: AUC0-6 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Description

AUC0-6 has been calculated using PK samples collected after GDC-0810 administration.

Time Frame

Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8

Title

Phase Ib: t/2 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Description

Time Frame

Cohort C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8

Title

Phase Ib: Cmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Description

Cmax has been calculated using PK samples collected after GDC-0810 administration.

Time Frame

Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Title

Phase Ib: Tmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Description

Tmax has been calculated using PK samples collected after GDC-0810 administration.

Time Frame

Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Title

Phase Ib: AUC0-6 of LHRH Agonist in Combination With GDC-0810 and/or an Palbociclib

Description

AUC0-6 has been calculated using PK samples collected after GDC-0810 administration.

Time Frame

Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Title

Phase Ib: t/2 of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Description

Time Frame

Cohort D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Phase 1a portion Histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of either locally recurrent disease not amenable to resection or radiation therapy with curative intent, or metastatic disease, both progressing after at least 6 months of hormonal therapy for estrogen receptor (ER) positive breast cancer ER-positive, human epidermal growth factor 2 (HER2) negative At least 2 months must have elapsed from the use of tamoxifen At least 6 months must have elapsed from the use of fulvestrant At least 2 weeks must have elapsed from the use of any other anticancer hormonal therapy At least 3 weeks must have elapsed from the use of any chemotherapy Postmenopausal status Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 Adequate organ function Phase Ib portion All above inclusion criteria, except: Postmenopausal status, pre- and peri-menopausal participants will also be included ECOG performance status less than 2 At least 2 months must have elapsed from the use of tamoxifen not applicable At least 6 months must have elapsed from the use of fulvestrant not applicable and plus: Documented sensitivity to prior hormonal therapy Cohort C1 (palbociclib combination cohorts): no prior treatment with cyclin-dependent kinase (CDK) 4/6 inhibitor Phase IIa portion All above inclusion criteria for Phase Ia, except: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 At least 6 months must have elapsed from the use of fulvestrant not applicable and plus: Cohort A only: confirmed estrogen receptor alpha (ESR1) mutation and presence of measurable disease as per RECIST v1.1 or evaluable bone disease Cohort A1 only: no prior fulvestrant allowed; at least 2 months must have elapsed from the use of tamoxifen Cohort A2 only: prior fulvestrant allowed Cohort B only: disease progression following no more than 1 prior treatment with an aromatase inhibitor in the advanced/metastatic setting Cohort B1 only: no prior fulvestrant allowed Cohort B2 only: prior fulvestrant allowed Exclusion Criteria: Phase 1a portion Untreated or symptomatic central nervous system (CNS) metastases Endometrial disorders More than 2 prior chemotherapy in the advanced/metastatic setting (prior adjuvant chemotherapy is allowed so long as it occurred greater than or equal to 12 months prior to enrollment) Current treatment with any systemic anticancer therapies for advanced disease Any significant cardiac dysfunction within 12 months prior to enrollment Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or upper gastrointestinal surgery including gastric resection Known human immunodeficiency virus (HIV) infection Known clinically significant history of liver disease Major surgery within 4 weeks prior to enrollment Radiation therapy within 2 weeks prior to enrollment Phase Ib portion - all above exclusion criteria, plus: Cohort C1 (palbociclib combination cohorts): history of venous thromboembolic event requiring therapeutic anticoagulation; vaginal bleeding within 2 months prior to enrollment Phase IIa portion - all above exclusion criteria, plus: Cohort A1, A2, and Cohort B2 only: more than 1 prior chemotherapy in the advanced/metastatic setting Cohort B1 only: prior chemotherapy in the advanced/metastatic setting

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

Ucsd Medical Center

City

San Diego

State/Province

California

ZIP/Postal Code

92103-8465

Country

United States

Facility Name

Massachusetts General Hospital.

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Dana Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

Washington University

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63128

Country

United States

Facility Name

Mount SInai Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

Facility Name

Seattle Cancer Care Alliance

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

Facility Name

Seoul National University Hospital

City

Seoul

ZIP/Postal Code

03080

Country

Korea, Republic of

Facility Name

Severance Hospital, Yonsei University Health System

City

Seoul

ZIP/Postal Code

03722

Country

Korea, Republic of

Facility Name

VU MEDISCH CENTRUM; Dept. of Medical Oncology

City

Amsterdam

ZIP/Postal Code

1081 HV

Country

Netherlands

Facility Name

Hospital Universitari Vall d'Hebron

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

City

Madrid

ZIP/Postal Code

28050

Country

Spain

Facility Name

Hospital Clinico Universitario de Valencia

City

Valencia

ZIP/Postal Code

46010

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

36401732

Citation

Bardia A, Mayer I, Winer E, Linden HM, Ma CX, Parker BA, Bellet M, Arteaga CL, Cheeti S, Gates M, Chang CW, Fredrickson J, Spoerke JM, Moore HM, Giltnane J, Friedman LS, Chow Maneval E, Chan I, Jhaveri K. The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 -) advanced/metastatic breast cancer. Breast Cancer Res Treat. 2023 Jan;197(2):319-331. doi: 10.1007/s10549-022-06797-9. Epub 2022 Nov 19.

Results Reference

derived

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