GDC-0084 With Radiation Therapy for People With PIK3CA-Mutated Solid Tumor Brain Metastases or Leptomeningeal Metastases
Primary Purpose
Brain Metastases, Leptomeningeal Metastasis
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GDC-0084
whole brain radiation therapy radiation
Sponsored by
About this trial
This is an interventional treatment trial for Brain Metastases focused on measuring GDC-0084, Radiation, PIK3CA Mutations, 19-359
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed solid tumor malignancies harboring PIK3CA mutations which include mutations in any of the following genes: PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3C2G, PIK3C3, INPP4A, INPP4B, INPPL1, INPP5D, PTEN, AKT1, AKT2, AKT3, and MTOR.
- Brain metastases and/or leptomeningeal metastases involving the brain demonstrated by MR imaging of the brain. For patients with brain metastases, measurable lesion by RANO-BM is required28. Patients with spine leptomeningeal metastases are eligible for the study if they have leptomeningeal metastases of the brain demonstrated by MRI imaging of the brain.
- KPS ≥ 70
- Age ≥ 18 years
- Able to provide informed consent.
- If a patient is on corticosteroid, he/she must be on a stable daily dose of < 4mg dexamethasone or equivalent. Patient does not need to be given corticosteroid as prophylaxis if not clinically indicated.
- No limit to prior therapies with the last systemic therapy ≥ 1 week from initiation of protocol therapy. Systemic therapy can resume after completion of protocol DLT assessment period.
- Patients with prior SRS are eligible, provided that there are new, non-irradiated brain lesions or leptomeningeal metastases. Patients must be ≥ 3 months post prior cranial radiation therapy.
- Patients with seizure history related to brain metastases or leptomeningeal metastases controlled on antiepileptic medications are eligible.
- Patient at reproductive potential must agree to practice an effective contraceptive method
- Patient must be able to swallow and retain oral medication
- Adequate organ function as assessed by laboratory tests.
Adequate bone marrow function
- Hemoglobin ≥ 8g/dL
- Absolute neutrophil count ≥1,000/mm^3
- Platelet count ≥ 100,000/mm^3
Adequate liver function
- Bilirubin ≤1.5 times upper limit normal (ULN)
- AST and ALT ≤ 2.5 times ULN
- Alkaline phosphatase ≤ 2 times ULN
- Adequate renal function ° BUN and Creatinine ≤ 1.5 times ULN
Exclusion Criteria:
- Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects tissue tolerances
- Patients with brain metastases eligible for single fraction stereotactic radiation therapy
- Serious medical co-morbidities precluding radiotherapy
- Insulin-treated diabetes; subjects with diabetes or impaired glucose tolerance that is not treated with insulin may be enrolled
- QT interval ≥ 450 msec on EKG
- Cardiac dysfunction defined as: myocardial infarction within 6 months of study entry, NYHA Class II/III/IV heart failure, unstable angina or unstable cardiac arrhythmias
- Known hypersensitivity or intolerance to GDC-0084 or to any other inhibitor of the PI3K/ Akt/ mTOR pathway
- Past medical history of interstitial lung disease, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active interstitial lung disease
- Subject receiving any medications or substances that are moderate and/or potent enzyme inducers or inhibitors which may have an effect on the metabolism of GDC-0084.
- Pregnant or lactating women.
Sites / Locations
- BAPTIST ALLIANCE - MCI (Data Collection Only)Recruiting
- Memorial Sloan Kettering Basking Ridge (Consent only)Recruiting
- Memorial Sloan Kettering Monmouth (All protocol activities)Recruiting
- Memorial Sloan Kettering Bergen (Consent only)Recruiting
- Memorial Sloan Kettering Commack (Consent only)Recruiting
- Memorial Sloan Kettering Westchester (All protocol activities)Recruiting
- Memorial Sloan Kettering Cancer Center (All protocol activities)Recruiting
- Memorial Sloan Kettering Nassau (Consent only)Recruiting
- University of Washington (Data Collection AND Data Analysis)Recruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Concurrent GDC-0084 with Radiation
Arm Description
GDC-0084 in 3 + 3 dose-escalation in 3 cohorts: 45, 60, 75 mg daily, with a potential de-escalation cohort to 30mg, to determine MTD in combination with whole brain radiation therapy radiation therapy to 30Gy in 10 fractions. Once MTD is determined, 12 additional patients will be treated with GDC-0084 at MTD in combination with whole brain radiation therapy.
Outcomes
Primary Outcome Measures
maximum tolerated dose (MTD)
Four dose levels will be examined and the maximum tolerated dose (MTD) will be identified.
The standard 3+3 dose-escalation scheme for this study is as follows. Patients will be accrued to the study in cohorts of 3. For any given dose an initial cohort of 3 patients will be treated at that dose.The dose level will be escalated if none of the 3 exhibits any dose limiting toxicity (DLT).
Secondary Outcome Measures
local recurrence rate
For patients with brain metastases, response determination will be determined using Response Assessment in Neuro-Oncology Brain Metastases criteria28. For patients with leptomeningeal metastases, response assessment will be determined by investigator based on MRI.
Full Information
NCT ID
NCT04192981
First Posted
December 6, 2019
Last Updated
July 20, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Kazia Therapeutics
1. Study Identification
Unique Protocol Identification Number
NCT04192981
Brief Title
GDC-0084 With Radiation Therapy for People With PIK3CA-Mutated Solid Tumor Brain Metastases or Leptomeningeal Metastases
Official Title
A Phase I Study With Expansion Cohort of Concurrent GDC-0084 With Radiation Therapy for Patients With Solid Tumor Brain Metastases or Leptomeningeal Metastases Harboring PI3K Pathway Mutations
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 6, 2019 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Kazia Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study will test the safety of the study drug, GDC-0084, in combination with radiation therapy in people who have solid tumor brain metastases or leptomeningeal metastases. All participants will have cancer with a PIK3CA mutation. The researchers will test increasing doses of GDC-0084 to find the highest dose that causes few or mild side effects in participants. The study will also try to find out if the combination of the study drug with radiation is effective against participants' cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Metastases, Leptomeningeal Metastasis
Keywords
GDC-0084, Radiation, PIK3CA Mutations, 19-359
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Single-arm, prospective trial
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Concurrent GDC-0084 with Radiation
Arm Type
Experimental
Arm Description
GDC-0084 in 3 + 3 dose-escalation in 3 cohorts: 45, 60, 75 mg daily, with a potential de-escalation cohort to 30mg, to determine MTD in combination with whole brain radiation therapy radiation therapy to 30Gy in 10 fractions. Once MTD is determined, 12 additional patients will be treated with GDC-0084 at MTD in combination with whole brain radiation therapy.
Intervention Type
Drug
Intervention Name(s)
GDC-0084
Intervention Description
GDC-0084 in 3 + 3 dose-escalation in 3 cohorts: 45, 60, 75 mg daily
Intervention Type
Radiation
Intervention Name(s)
whole brain radiation therapy radiation
Intervention Description
30Gy in 10 fractions
Primary Outcome Measure Information:
Title
maximum tolerated dose (MTD)
Description
Four dose levels will be examined and the maximum tolerated dose (MTD) will be identified.
The standard 3+3 dose-escalation scheme for this study is as follows. Patients will be accrued to the study in cohorts of 3. For any given dose an initial cohort of 3 patients will be treated at that dose.The dose level will be escalated if none of the 3 exhibits any dose limiting toxicity (DLT).
Time Frame
1 year
Secondary Outcome Measure Information:
Title
local recurrence rate
Description
For patients with brain metastases, response determination will be determined using Response Assessment in Neuro-Oncology Brain Metastases criteria28. For patients with leptomeningeal metastases, response assessment will be determined by investigator based on MRI.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed solid tumor malignancies harboring PIK3CA mutations which include mutations in any of the following genes: PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3C2G, PIK3C3, INPP4A, INPP4B, INPPL1, INPP5D, PTEN, AKT1, AKT2, AKT3, and MTOR.
Brain metastases and/or leptomeningeal metastases involving the brain demonstrated by MR imaging of the brain. For patients with brain metastases, measurable lesion by RANO-BM is required28. Patients with spine leptomeningeal metastases are eligible for the study if they have leptomeningeal metastases of the brain demonstrated by MRI imaging of the brain.
KPS ≥ 70
Age ≥ 18 years
Able to provide informed consent.
If a patient is on corticosteroid, he/she must be on a stable daily dose of < 4mg dexamethasone or equivalent. Patient does not need to be given corticosteroid as prophylaxis if not clinically indicated.
No limit to prior therapies with the last systemic therapy ≥ 1 week from initiation of protocol therapy. Systemic therapy can resume after completion of protocol DLT assessment period.
Patients with prior SRS are eligible, provided that there are new, non-irradiated brain lesions or leptomeningeal metastases. Patients must be ≥ 3 months post prior cranial radiation therapy.
Patients with seizure history related to brain metastases or leptomeningeal metastases controlled on antiepileptic medications are eligible.
Patient at reproductive potential must agree to practice an effective contraceptive method
Patient must be able to swallow and retain oral medication
Adequate organ function as assessed by laboratory tests.
Adequate bone marrow function
Hemoglobin ≥ 8g/dL
Absolute neutrophil count ≥1,000/mm^3
Platelet count ≥ 100,000/mm^3
Adequate liver function
Bilirubin ≤1.5 times upper limit normal (ULN)
AST and ALT ≤ 2.5 times ULN
Alkaline phosphatase ≤ 2 times ULN
Adequate renal function ° BUN and Creatinine ≤ 1.5 times ULN
Exclusion Criteria:
Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects tissue tolerances
Patients with brain metastases eligible for single fraction stereotactic radiation therapy
Serious medical co-morbidities precluding radiotherapy
Insulin-treated diabetes; subjects with diabetes or impaired glucose tolerance that is not treated with insulin may be enrolled
QT interval ≥ 450 msec on EKG
Cardiac dysfunction defined as: myocardial infarction within 6 months of study entry, NYHA Class II/III/IV heart failure, unstable angina or unstable cardiac arrhythmias
Known hypersensitivity or intolerance to GDC-0084 or to any other inhibitor of the PI3K/ Akt/ mTOR pathway
Past medical history of interstitial lung disease, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active interstitial lung disease
Subject receiving any medications or substances that are moderate and/or potent enzyme inducers or inhibitors which may have an effect on the metabolism of GDC-0084.
Pregnant or lactating women.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Brandon Imber, MD, PhD
Phone
6312126346
Email
imberb@mskcc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Eli Diamond, MD
Phone
212-610-0243
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brandon Imber, MD, PhD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
BAPTIST ALLIANCE - MCI (Data Collection Only)
City
Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rupesh Kotecha, MD
Phone
786-596-2000
Facility Name
Memorial Sloan Kettering Basking Ridge (Consent only)
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brandon Imber, MD, PhD
Phone
631-212-6346
Facility Name
Memorial Sloan Kettering Monmouth (All protocol activities)
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brandon Imber, MD. PhD
Phone
631-212-6346
Facility Name
Memorial Sloan Kettering Bergen (Consent only)
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brandon Imber, MD, PhD
Phone
631-212-6346
Facility Name
Memorial Sloan Kettering Commack (Consent only)
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brandon Imber, MD, PhD
Phone
631-212-6346
Facility Name
Memorial Sloan Kettering Westchester (All protocol activities)
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brandon Imber, MD, PhD
Phone
631-212-6346
Facility Name
Memorial Sloan Kettering Cancer Center (All protocol activities)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brandon Imber, MD, PhD
Phone
631-212-6346
Facility Name
Memorial Sloan Kettering Nassau (Consent only)
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brandon Imber, MD
Phone
631-212-6346
Facility Name
University of Washington (Data Collection AND Data Analysis)
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jonathan Yang, MD
Phone
855-557-0555
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center
Learn more about this trial
GDC-0084 With Radiation Therapy for People With PIK3CA-Mutated Solid Tumor Brain Metastases or Leptomeningeal Metastases
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