Clinical Trials /

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

NCT04192981

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 19-359
  • NCT ID: NCT04192981

Conditions

  • Brain Metastases
  • Leptomeningeal Metastasis

Interventions

DrugSynonymsArms
GDC-0084Concurrent GDC-0084 with Radiation

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Concurrent GDC-0084 with RadiationExperimentalGDC-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.
  • GDC-0084

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:maximum tolerated dose (MTD)
Time Frame:1 year
Safety Issue:
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).

Secondary Outcome Measures

Measure:local recurrence rate
Time Frame:1 year
Safety Issue:
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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • GDC-0084
  • Radiation
  • PIK3CA Mutations
  • 19-359

Last Updated

February 12, 2020