Breast CancerPhase 1/2NCT01823835
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
A Phase 1/2 study testing GDC-0810, LHRH Agonist and Palbociclib in people with Breast Cancer, run by Genentech, Inc. at 14 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- GDC-0810, LHRH Agonist and Palbociclib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 152 participants
- Where
- 14 sitesin 4 countries
- Study dates
- 29 Dec 2014to 13 Mar 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
14 sites in 4 countries.
14 sites in 4 countries
United States8 sites
Massachusetts General Hospital.
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Mount SInai Medical Center
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Ucsd Medical Center
San Diego, California, 92103-8465
Seattle Cancer Care Alliance
Seattle, Washington, 98109
Washington University
St Louis, Missouri, 63128
Spain3 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
Madrid, 28050
Hospital Clinico Universitario de Valencia
Valencia, 46010
South Korea2 sites
Seoul National University Hospital
Seoul, 03080
Severance Hospital, Yonsei University Health System
Seoul, 03722
Netherlands1 site
VU MEDISCH CENTRUM; Dept. of Medical Oncology
Amsterdam, 1081 HV
About this study
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
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.
- Conditions
- Breast Cancer
- Being tested
- GDC-0810, LHRH Agonist, Palbociclib
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GDC-0810Drug
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).
LHRH AgonistDrug
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.
PalbociclibDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Phase Ia - Cohort 1 | Experimental | 100 mg GDC-0810 once daily (QD) in fasting state. Receives: Drug: GDC-0810 |
| Phase Ia - Cohort 2 | Experimental | 200 mg GDC-0810 QD in fasting state. Receives: Drug: GDC-0810 |
| Phase Ia - Cohort 3 | Experimental | 400 mg GDC-0810 QD in fasting state. Receives: Drug: GDC-0810 |
| Phase Ia - Cohort 4 | Experimental | 600 mg GDC-0810 QD in fasting state. Receives: Drug: GDC-0810 |
| Phase Ia - Cohort 5 | Experimental | 600 mg GDC-0810 QD in non-fasting state. Receives: Drug: GDC-0810 |
| Phase Ia - Cohort 6 | Experimental | 300 mg GDC-0810 twice daily (BID) in fasting state. Receives: Drug: GDC-0810 |
| Phase Ia - Cohort 7 | Experimental | 800 mg GDC-0810 QD in fasting state. Receives: Drug: GDC-0810 |
| Phase Ia - Cohort 8 | Experimental | 800 mg GDC-0810 QD in non-fasting state. Receives: Drug: GDC-0810 |
| Phase Ia - Cohort 9 | Experimental | 400 mg GDC-0810 BID in fasting state. Receives: Drug: GDC-0810 |
| Phase IIa - Cohort A1 | Experimental | 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). Receives: Drug: GDC-0810 |
| Phase IIa - Cohort A2 | Experimental | 600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and confirmed ER-a (ESR1) mutation of the LBD. Receives: Drug: GDC-0810 |
| Phase IIa - Cohort B1 | Experimental | 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). Receives: Drug: GDC-0810 |
| Phase IIa - Cohort B2 | Experimental | 600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and progressed following ≤1 prior therapy with an AI. Receives: Drug: GDC-0810 |
| Phase Ib - Cohort C1 | Experimental | 400 mg GDC-0810 + 125 mg Palbociclib QD. Receives: Drug: GDC-0810; Drug: Palbociclib |
| Phase Ib - Cohort D1 | Experimental | ≤600 mg GDC-0810 QD + LHRH agonist once monthly. Receives: Drug: GDC-0810; Drug: LHRH Agonist |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Day -7 through the first cycle (28 days) of treatment (35 days total)
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.
Measured: Day -7 through the first cycle (28 days) of treatment (35 days total)
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.
Measured: Screening and every 8 weeks from Cycle 1 Day 1 until Cycle 12, thereafter every 3 months until disease progression (up to 3 years)
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.
Measured: Screening and every 8 weeks from Cycle 1 Day 1 until Cycle 12, thereafter every 3 months until disease progression (up to 3 years)
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.
Measured: first cycle (Days 1 to 28 of a 28-day schedule)
Secondary outcomes (21)
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.
Measured: up to 3 years
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours postdose
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.
Measured: Day -7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose
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
Measured: Day -7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8
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.
Measured: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8
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.
Measured: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8
Phase Ib: t/2 of Palbociclib in Combination With GDC-0810 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.
Measured: Cohort C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8
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.
Measured: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1
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.
Measured: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1
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.
Measured: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1
Phase Ib: t/2 of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib
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.
Measured: Cohort D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2013 (estimated)
- Study start29 Dec 2014
- Primary completion13 Mar 2020
- Study completion13 Mar 2020
Why it stopped: The Sponsor decided to halt the development of GDC-0810, but not due to any safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 152 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01823835
- Sponsor's protocol ID
- GO29642
- Other IDs
- 2014-004852-77, 2014
- Status last verified
- May 2021
- First submitted
- 25 Mar 2013
- Last updated
- 18 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 36401732
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01823835
- Acronym / sponsor ID
- GO29642
- Conditions
- Breast Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The Sponsor decided to halt the development of GDC-0810, but not due to any safety concerns.
- Enrolment
- 152 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- 29 Dec 2014 (actual)
- Primary completion
- 13 Mar 2020 (actual)
- Study completion
- 13 Mar 2020 (actual)
- First posted
- 4 Apr 2013 (estimated)
- Results
- Posted 18 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 15
| Arm | Type | Receives |
|---|---|---|
| Phase Ia - Cohort 1 | Experimental | Drug: GDC-0810100 mg GDC-0810 once daily (QD) in fasting state. |
| Phase Ia - Cohort 2 | Experimental | Drug: GDC-0810200 mg GDC-0810 QD in fasting state. |
| Phase Ia - Cohort 3 | Experimental | Drug: GDC-0810400 mg GDC-0810 QD in fasting state. |
| Phase Ia - Cohort 4 | Experimental | Drug: GDC-0810600 mg GDC-0810 QD in fasting state. |
| Phase Ia - Cohort 5 | Experimental | Drug: GDC-0810600 mg GDC-0810 QD in non-fasting state. |
| Phase Ia - Cohort 6 | Experimental | Drug: GDC-0810300 mg GDC-0810 twice daily (BID) in fasting state. |
| Phase Ia - Cohort 7 | Experimental | Drug: GDC-0810800 mg GDC-0810 QD in fasting state. |
| Phase Ia - Cohort 8 | Experimental | Drug: GDC-0810800 mg GDC-0810 QD in non-fasting state. |
| Phase Ia - Cohort 9 | Experimental | Drug: GDC-0810400 mg GDC-0810 BID in fasting state. |
| Phase IIa - Cohort A1 | Experimental | Drug: GDC-0810600 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). |
| Phase IIa - Cohort A2 | Experimental | Drug: GDC-0810600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and confirmed ER-a (ESR1) mutation of the LBD. |
| Phase IIa - Cohort B1 | Experimental | Drug: GDC-0810600 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). |
| Phase IIa - Cohort B2 | Experimental | Drug: GDC-0810600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and progressed following ≤1 prior therapy with an AI. |
| Phase Ib - Cohort C1 | Experimental | Drug: GDC-0810, Drug: Palbociclib400 mg GDC-0810 + 125 mg Palbociclib QD. |
| Phase Ib - Cohort D1 | Experimental | Drug: GDC-0810, Drug: LHRH Agonist≤600 mg GDC-0810 QD + LHRH agonist once monthly. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GDC-0810GDC-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). | Drug | Phase IIa - Cohort A1, Phase IIa - Cohort A2, Phase IIa - Cohort B1, Phase IIa - Cohort B2, 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 Ib - Cohort C1, Phase Ib - Cohort D1 |
| LHRH AgonistLHRH 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. | Drug | Phase Ib - Cohort D1 |
| PalbociclibPalbociclib administered orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, GDC-0810 drug supply exhausted, or study termination (up to 3 years). | Drug | Phase Ib - Cohort C1 |
Primary outcome
Phase Ia: Maximum Tolerated Dose of GDC-0810 When Used as a Single Agent
Time frame: Day -7 through the first cycle (28 days) of treatment (35 days total)
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
Time frame: Day -7 through the first cycle (28 days) of treatment (35 days total)
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
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)
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)
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)
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
Time frame: first cycle (Days 1 to 28 of a 28-day schedule)
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.
21 secondary outcomes
All Phases: Percentage of Participants With Adverse Events (AEs)
Time frame: up to 3 years
Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites
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
Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites
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
Phase Ia: Area Under the Concentration-time Curves at 6 Hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites
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
Phase Ia: Area Under the Concentration-time Curves at 24 Hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites
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
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf)
Time frame: Day-7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours postdose
Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent
Time frame: Day -7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose
Phase Ia: Apparent Clearance (Cl/F)
Time frame: Day -7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 hours postdose
Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula
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
Phase Ib: Cmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist
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
Phase Ib: Tmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist
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
Phase Ib: AUC0-6 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist
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
Phase Ib: t/2 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist
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
Phase Ib: Cmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist
Time frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8
Phase Ib: Tmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist
Time frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8
Phase Ib: AUC0-6 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist
Time frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8
Phase Ib: t/2 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist
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
Phase Ib: Cmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib
Time frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1
Phase Ib: Tmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib
Time frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1
Phase Ib: AUC0-6 of LHRH Agonist in Combination With GDC-0810 and/or an Palbociclib
Time frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1
Phase Ib: t/2 of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36401732Bardia 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
14 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing GDC-0810, LHRH Agonist and Palbociclib in people with Breast Cancer, run by Genentech, Inc. at 14 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 30 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Spain, South Korea, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ia: Maximum Tolerated Dose of GDC-0810 When Used as a Single Agent (time frame: Day -7 through the first cycle (28 days) of treatment (35 days total)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01823835, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2021.