GDC-0084 With Radiation Therapy for People With PIK3CA-Mutated Solid Tumor Brain Metastases or Leptomeningeal Metastases

Brain Metastases Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04192981
• Other study ID #: 19-359
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 6, 2019
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 21
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Leptomeningeal Metastasis
• Meningeal Carcinomatosis
• Neoplasm Metastasis
• Neoplasms, Second Primary

Intervention

Drug:
• GDC-0084
GDC-0084 in 3 + 3 dose-escalation in 3 cohorts: 45, 60, 75 mg daily

Radiation:
• whole brain radiation therapy radiation
30Gy in 10 fractions

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (Consent only)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Commack (Consent only)	Commack	New York
United States	Memorial Sloan Kettering Westchester (All protocol activities)	Harrison	New York
United States	BAPTIST ALLIANCE - MCI (Data Collection Only)	Miami	Florida
United States	Memorial Sloan Kettering Monmouth (All protocol activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Consent only)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center (All protocol activities)	New York	New York
United States	University of Washington (Data Collection AND Data Analysis)	Seattle	Washington
United States	Memorial Sloan Kettering Nassau (Consent only)	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Kazia Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	1 year
Secondary	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.	1 year

External Links

•   Memorial Sloan Kettering Cancer Center