ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    GDC-0077
Previous Study | Return to List | Next Study

To Evaluate the Safety, Tolerability, and Pharmacokinetics of GDC-0077 Single Agent in Participants With Solid Tumors and in Combination With Endocrine and Targeted Therapies in Participants With Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03006172
Recruitment Status : Recruiting
First Posted : December 30, 2016
Last Update Posted : December 14, 2017
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Brief Summary:
This is an open-label, multicenter, Phase I study designed to evaluate the safety, tolerability, and pharmacokinetics of GDC-0077 administered orally as a single agent in participants with locally advanced or metastatic Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA)-mutant solid tumors, including breast cancer, and in combination with standard-of-care endocrine and targeted therapies for the treatment of locally advanced or metastatic PIK3CA-mutant hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Participants will be enrolled in two stages: a dose-escalation stage (Stage I) and an expansion stage (Stage II). Participants will be assigned to one of four regimens: GDC-0077 as a single agent (Arm A), GDC-0077 in combination with palbociclib and letrozole (Arm B), GDC-0077 in combination with letrozole (Arm C), or GDC-0077 in combination with fulvestrant (Arm D).

Condition or disease Intervention/treatment Phase
Breast Cancer Solid Tumor Drug: GDC-0077 Drug: Fulvestrant Drug: Letrozole Drug: Palbociclib Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 156 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0077 as a Single Agent in Patients With Locally Advanced or Metastatic PIK3CA-Mutant Solid Tumors and in Combination With Endocrine and Targeted Therapies in Patients With Locally Advanced or Metastatic PIK3CA-Mutant Hormone-Receptor Positive Breast Cancer
Actual Study Start Date : November 30, 2016
Estimated Primary Completion Date : February 29, 2020
Estimated Study Completion Date : February 29, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Stage I Arm A: GDC-0077 Single Agent
Participants will receive GDC-0077 in escalating dose levels with starting dose of 6 milligrams (mg). Participants will receive single dose of GDC-0077 on Day 1 of Cycle 1 followed by once daily from Day 8 of Cycle 1. (Cycle length: 35 days for Cycle 1 and 28 days for all other cycles). Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
Drug: GDC-0077
Participants will receive oral GDC-0077 once daily. For dose escalation, the dose will be increased by up to 100% of the preceding dose level for each successive cohort, until a safety threshold is met.
Other Name: RO7113755
Experimental: Stage I Arm B: GDC-0077 + Palbociclib + Letrozole
Participants will receive GDC-0077 in escalating dose levels (starting dose 3 mg) on Days 1-28, palbociclib on Days 1−21, and letrozole on Days 1−28 of each 28-day cycle. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
Drug: GDC-0077
Participants will receive oral GDC-0077 once daily. For dose escalation, the dose will be increased by up to 100% of the preceding dose level for each successive cohort, until a safety threshold is met.
Other Name: RO7113755
Drug: Letrozole
Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1−28 of each cycle.
Drug: Palbociclib
Participants will receive once daily oral doses of palbociclib 125 mg on Days 1−21 of each cycle.
Experimental: Stage I Arm C: GDC-0077 + Letrozole
Participants will receive GDC-0077 in escalating dose levels along with letrozole on Days 1−28 of each 28-day cycle. The starting dose of GDC-0077 will not exceed the starting dose in Stage I Arm A. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
Drug: GDC-0077
Participants will receive oral GDC-0077 once daily. For dose escalation, the dose will be increased by up to 100% of the preceding dose level for each successive cohort, until a safety threshold is met.
Other Name: RO7113755
Drug: Letrozole
Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1−28 of each cycle.
Experimental: Stage II Arm B: GDC-0077 + Palbociclib + Letrozole
Participants will receive GDC-0077 on Days 1-28 in combination with palbociclib on Days 1-21 and letrozole on Days 1-28 of each 28-day cycle. Dose of GDC-0077 will be decided based on the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
Drug: GDC-0077
Participants will receive oral GDC-0077 once daily. For dose escalation, the dose will be increased by up to 100% of the preceding dose level for each successive cohort, until a safety threshold is met.
Other Name: RO7113755
Drug: Letrozole
Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1−28 of each cycle.
Drug: Palbociclib
Participants will receive once daily oral doses of palbociclib 125 mg on Days 1−21 of each cycle.
Experimental: Stage II Arm C: GDC-0077 + Letrozole
Participants will receive GDC-0077 in combination with letrozole on Days 1-28 of each 28-day cycle. Dose of GDC-0077 will be decided based on the results of Stage I Arm C. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
Drug: GDC-0077
Participants will receive oral GDC-0077 once daily. For dose escalation, the dose will be increased by up to 100% of the preceding dose level for each successive cohort, until a safety threshold is met.
Other Name: RO7113755
Drug: Letrozole
Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1−28 of each cycle.
Experimental: Stage II Arm D: GDC-0077 + Fulvestrant
Participants will receive GDC-0077 on Days 1-28 in combination with fulvestrant on Day 1 and 15 of Cycle 1 and then on Day 1 from Cycle 2 (cycle length: 28 days). Dose of GDC-0077 will be decided based on the results of Stage I Arm C. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
Drug: GDC-0077
Participants will receive oral GDC-0077 once daily. For dose escalation, the dose will be increased by up to 100% of the preceding dose level for each successive cohort, until a safety threshold is met.
Other Name: RO7113755
Drug: Fulvestrant
Participants will receive fulvestrant 500 mg, administered intramuscularly on Days 1 and 15 of Cycle 1. For subsequent cycles, participants will receive fulvestrant intramuscularly on Day 1 of each cycle.



Primary Outcome Measures :
  1. Stage 1: Percentage of Participants With Dose Limiting Toxicities [ Time Frame: Day 1 up to Day 28 (for Stage 1 Arm A: Day 1 up to Day 35) ]
  2. Recommended Phase II Dose of GDC-0077 [ Time Frame: Day 1 up to Day 28 (for Stage 1 Arm A: Day 1 up to Day 35) ]
  3. Percentage of Participants With Adverse Events and Serious Adverse Events [ Time Frame: Day 1 up to 3.5 years ]

Secondary Outcome Measures :
  1. Area Under the Concentration Time-Curve (AUC) from Time Zero to Infinity (AUCinf) of GDC-0077 [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to end of study (EOS; up to approximately 3.5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  2. AUC from Time Zero to Dosing Interval (AUC0-tau) of GDC-0077 [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 3.5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  3. Half-Life of GDC-0077 [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 3.5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  4. Maximum Plasma Concentration (Cmax) of GDC-0077 [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 3.5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  5. Minimum Plasma Concentration (Cmin) of GDC-0077 [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 3.5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  6. Time to Cmax (tmax) of GDC-0077 [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 3.5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  7. Apparent Clearance (CL/F) of GDC-0077 [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 3.5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  8. Accumulation Ratio (AR) of GDC-0077 at Steady-State [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 3.5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  9. AUC of Palbociclib [ Time Frame: Predose (0-2 hours before GDC-0077) dosing) on Cycle 1 Day 1 up to Cycle 6; Cycle length=28 days ]
  10. Cmax of Palbociclib [ Time Frame: Predose (0-2 hours before GDC-0077) dosing) on Cycle 1 Day 1 up to Cycle 6; Cycle length=28 days ]
  11. AUC of Letrozole [ Time Frame: Predose (0-2 hours before GDC-0077 dosing) on Cycle 1 Day 1 up to EOS (up to approximately 3.5 years); Cycle length=28 days ]
  12. Cmax of Letrozole [ Time Frame: Predose (0-2 hours before GDC-0077 dosing) on Cycle 1 Day 1 up to EOS (up to approximately 3.5 years); Cycle length=28 days ]
  13. AUC of Fulvestrant [ Time Frame: Cycle 1 Day 2 up to EOS (up to approximately 3.5 years); Cycle length=28 days. ]
  14. Cmax of Fulvestrant [ Time Frame: Cycle 1 Day 2 up to EOS (up to approximately 3.5 years); Cycle length=28 days. ]
  15. Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (v1.1) [ Time Frame: Baseline up to occurrence of complete response (CR) or partial response (PR) on 2 consecutive occasions >/=4 weeks apart (up to approximately 3.5 years) ]
  16. Duration of Response, as Assessed by RECIST v1.1 [ Time Frame: From first occurrence of a documented objective response (CR or PR) to disease progression or death from any cause, whichever occurs first (up to approximately 3.5 years) ]
  17. Percentage of Participants With Clinical Benefit as Assessed by RECIST v1.1 [ Time Frame: Baseline up to disease progression or death from any cause, whichever occurs first (up to approximately 3.5 years) ]
  18. Progression Free Survival (PFS) as Assessed by RECIST v1.1 [ Time Frame: Baseline up to disease progression or death from any cause, whichever occurs first (up to approximately 3.5 years) ]
  19. Change in Maximum Standard Uptake Value (SUV) of Tumor Regions of Interest (as assessed by [18] F-fluorodeoxyglucose-positron emission tomography) From Baseline to Approximately 2 Weeks of GDC-0077 Treatment [ Time Frame: Baseline, Week 2 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Evaluable or measurable disease per RECIST, Version 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy of greater than or equal to (≥) 12 weeks
  • Adequate hematologic and organ function, including blood counts, liver and kidney function

Stage I Arm A (GDC-0077):

  • Locally advanced, recurrent, or metastatic, PIK3CA mutant, incurable solid tumor malignancy, including breast cancer

Stages I and II, Arm B:

  • Postmenopausal female participants with histologically documented locally advanced or metastatic PIK3CA-mutant HR+/HER2- breast cancer
  • Absolute neutrophil count ≥ 1500 per microliter

Stages I and II, Arm C or Stage II Arm D:

  • Postmenopausal female participants with locally advanced or metastatic PIK3CA-mutant HR+/HER2− breast cancer

Stages I and II:

  • All participants must provide tumor tissue from the primary or metastatic tumor site obtained from a prior or new biopsy or surgical procedure for detection of PIK3CA mutation by central laboratory test. Confirmation of adequate tissue is required prior to enrollment. For participants enrolled to biopsy cohorts or who consent to optional tumor biopsies, the pretreatment tumor biopsy may be used

Exclusion Criteria:

  • Inflammatory or metaplastic breast cancer
  • History of leptomeningeal disease
  • Type 1 or 2 diabetes requiring anti-hyperglycemic medication
  • Inability or unwillingness to swallow pills
  • Malabsorption syndrome or other condition that would interfere with enteral absorption
  • Known and untreated, or active central nervous system metastases
  • Uncontrolled pleural effusion or ascites
  • Serious infection requiring antibiotics
  • Concurrent ocular or intraocular condition that requires medical or surgical intervention to prevent or treat vision loss
  • Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis
  • Daily supplemental oxygen
  • History of or active inflammatory disease or active bowel inflammation
  • Symptomatic hypercalcemia requiring bisphosphonate or denosumab therapy
  • Significant traumatic injury or major surgical procedure within 4 weeks prior to starting study treatment
  • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  • Treatment with chemotherapy, immunotherapy, or biologic therapy as anti-cancer therapy within 3 weeks, or treatment with endocrine therapy or kinase inhibitors within 2 weeks, prior to starting study treatment, except for premenopausal participants with breast cancer who may continue Gonadotropin-releasing hormone agonist therapy
  • Radiation therapy as cancer therapy within 4 weeks, or palliative radiation to bony metastases within 2 weeks, prior to starting study treatment
  • History of other malignancy within 5 years, except for treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
  • History of or active ventricular dysrhythmias or congestive heart failure requiring medication or symptomatic coronary heart disease
  • Congenital long QT syndrome, prolonged QT interval, or family history of sudden unexplained death or long QT syndrome
  • Current treatment with medications known to prolong the QT interval

Stage I:

  • History of significant toxicity related to another phosphatidylinositol 3-kinase (PI3K) inhibitor or mammalian target of rapamycin (mTOR) inhibitor requiring treatment discontinuation
  • Stage I Arm A: Pregnancy, lactation, or intention to become pregnant or fathering a child during the study
  • Stage I Arm B: history of significant toxicity related to cyclin-dependent kinase (CDK)4/6 inhibitor, bone marrow transplant or extensive radiotherapy to ≥25 percent (%) of bone marrow

Stage II:

  • Prior treatment with >1 chemotherapy regimen for metastatic disease
  • Prior treatment with PI3K inhibitor
  • History of significant toxicity related to mTOR inhibitor requiring treatment discontinuation
  • Stage II Arm B: prior CDK4/6 inhibitor treatment, bone marrow transplant or extensive radiotherapy to ≥25% of bone marrow

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03006172


Contacts
Contact: Reference Study ID Number: GO39374 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
United States, Massachusetts
Massachusetts General Hospital. Recruiting
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Canada, Ontario
Philippe Bedard Clinic Toronto Recruiting
Toronto, Ontario, Canada, M5G 1L7
France
Institut Bergonie Not yet recruiting
Bordeaux, France, 33076
Institut Gustave Roussy Recruiting
Villejuif, France, 94805
Spain
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Hospital Clinico Universitario de Valencia Recruiting
Valencia, Spain, 46010
United Kingdom
Barts and the London NHS Trust. Recruiting
London, United Kingdom, EC1M 6BQ
Royal Marsden Hospital Not yet recruiting
London, United Kingdom, SW3 6JJ
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT03006172     History of Changes
Other Study ID Numbers: GO39374
2016-003022-17 ( EudraCT Number )
First Posted: December 30, 2016    Key Record Dates
Last Update Posted: December 14, 2017
Last Verified: December 2017

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Fulvestrant
Palbociclib
Estradiol
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Estrogens
Hormones
Protein Kinase Inhibitors