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

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: NCT04192981
Recruitment Status : Recruiting
First Posted : December 10, 2019
Last Update Posted : February 17, 2020
Sponsor:
Collaborator:
Kazia Therapeutics
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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.

Condition or disease Intervention/treatment Phase
Brain Metastases Leptomeningeal Metastasis Drug: GDC-0084 Radiation: whole brain radiation therapy radiation Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Single-arm, prospective trial
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 6, 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Arm Intervention/treatment
Experimental: Concurrent GDC-0084 with Radiation
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.
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




Primary Outcome Measures :
  1. maximum tolerated dose (MTD) [ Time Frame: 1 year ]

    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 :
  1. local recurrence rate [ Time Frame: 1 year ]
    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.



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.


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

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): NCT04192981


Contacts
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Contact: T. Jonathan Yang, MD, PhD 212-639-8157 yangt@mskcc.org
Contact: Eli Diamond, MD 212-610-0243

Locations
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United States, New Jersey
Memoral Sloan Kettering Basking Ridge (Consent only) Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: T. Jonathan Yang, MD, PhD    212-639-8157      
Memoral Sloan Kettering Monmouth (All protocol activities) Recruiting
Middletown, New Jersey, United States, 07748
Contact: T. Jonathan Yang, MD. PhD    212-639-8157      
Memorial Sloan Kettering Monmouth (All protocol activities) Recruiting
Middletown, New Jersey, United States, 07748
Contact: T. Jonathan Yang, MD, PhD    212-639-8157      
Memorial Sloan Kettering Bergen (Consent only) Recruiting
Montvale, New Jersey, United States, 07645
Contact: T. Jonathan Yang, MD, PhD    212-639-8157      
United States, New York
Memorial Sloan Kettering Commack (Consent only) Recruiting
Commack, New York, United States, 11725
Contact: T. Jonathan Yang, MD, PhD    212-639-8157      
Memoral Sloan Kettering Westchester (All protocol activities) Recruiting
Harrison, New York, United States, 10604
Contact: T. Jonathan Yang, MD, PhD    212-639-8157      
Memorial Sloan Kettering Cancer Center (All protocol activities) Recruiting
New York, New York, United States, 10065
Contact: T. Jonathan Yang, MD, PhD    212-639-8157      
Memorial Sloan Kettering Nassau (Consent only) Recruiting
Uniondale, New York, United States, 11553
Contact: T. Jonathan Yang, MD    212-639-8157      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Kazia Therapeutics
Investigators
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Principal Investigator: T. Jonathan Yang, MD, PhD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04192981    
Other Study ID Numbers: 19-359
First Posted: December 10, 2019    Key Record Dates
Last Update Posted: February 17, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
GDC-0084
Radiation
PIK3CA Mutations
19-359
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Meningeal Carcinomatosis
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Meningeal Neoplasms