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Paxalisib (GDC-0084) In Recurrent Or Refractory PCNSL

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. Identifier: NCT04906096
Recruitment Status : Recruiting
First Posted : May 28, 2021
Last Update Posted : July 12, 2022
Kazia Therapeutics Limited
Information provided by (Responsible Party):
Lakshmi Nayak, Dana-Farber Cancer Institute

Brief Summary:
This research study is studying a drug called Paxalisib (GDC-0084) as a possible treatment for primary central nervous system lymphoma (PCNSL)

Condition or disease Intervention/treatment Phase
Primary Central Nervous System Lymphoma Non-Hodgkin Lymphoma of Extranodal Site Drug: PAXALISIB Phase 2

Detailed Description:

This is an open-label, phase 2 study to determine the efficacy of Paxalisib (GDC-0084) in 25 patients with recurrent or refractory primary central nervous system lymphoma (R/R PCNSL.

  • The name of the study drug involved in this study is Paxalisib (GDC-0084).
  • The research study procedures include: screening for eligibility and study treatment including evaluations and follow up visits.
  • It is expected that about 25 participants will take part in this research study for up to 24 months as long as there is no serious side effects and disease progression.

This research study is a Phase 2 clinical trial. Phase 2 clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied. The U.S. Food and Drug Administration (FDA) has not approved Paxalisib for this specific disease but it has been approved for other uses.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Paxalisib (GDC-0084) in Recurrent or Refractory Primary Central Nervous System Lymphoma (PCNSL)
Actual Study Start Date : June 1, 2021
Estimated Primary Completion Date : May 1, 2023
Estimated Study Completion Date : May 1, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: PAXALISIB

The research study procedures include: screening for eligibility and study treatment including evaluations and follow up visits.

  • Paxalisib (GDC-0084)
  • Each study treatment cycle lasts 28 days, up to 24 months.
Each study treatment cycle lasts 28 days, up to 24 months. Oral, daily, dosage per protocol
Other Name: GDC-0084

Primary Outcome Measures :
  1. Number of participants with Objective Response Rate (ORR) [ Time Frame: Up to 24 Months ]
    The Objective Response (ORR) is defined as a complete, unconfirmed complete or partial response as determined by the investigator assessment using IPCG criteria

Secondary Outcome Measures :
  1. Number of participants with Durable Objective Response Rate (ORR) [ Time Frame: Up to 24 Months ]
    Durable ORR will be defined as confirmed objective responses (CR, uCR and PR) by IPCG criteria that are durable for ≥ 6 months

  2. Overall Survival [ Time Frame: Up to 24 Months ]
    defined from the date of the 1st dose of paxalisib to the date of death or last follow-up. If a participant is still alive, she/he will be censored on the date of last followup.

  3. Progression Free Survival (PFS) [ Time Frame: up to 24 Months ]
    defined from the date of 1st dose of paxalisib to the date of progression based on IPCG criteria or death, if progression does not occur. All progressors will be included regardless of whether progression occurs while the participant was taking the study drug or previously discontinued the study drug

  4. Number of cumulative treatment-emergent adverse events (TEAEs) [ Time Frame: up to 24 Months ]
    Incidence of TEAEs, grade 3-5 TEAEs, SAEs (serious adverse events) and TEAEs leading to discontinuation of study treatment.

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

Inclusion Criteria:

  • Participants must be able to understand and willing to sign a written informed consent document.
  • Participant must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
  • Participant must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study.
  • Participants must be at least 18 years old on day of signing informed consent.
  • Participants must have a Karnofsky Performance Status (KPS) ≥ 70
  • Participants must have histologically confirmed R/R primary DLBCL CNS lymphoma (from brain biopsy, CSF or vitreous biopsy).
  • Participants should have evidence of refractory or recurrent disease on MRI with measurable or evaluable enhancing disease.
  • Participants must have recovered to ≤ grade 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy; exception, participants with ≤ grade 2 neuropathy may be eligible.
  • Participant with dexamethasone requirement of ≤ 8mg/day or bioequivalent with corticosteroid usage at a stable or decreasing dose 2 weeks prior to screening.
  • Participants must be able to undergo MRI.
  • Participants must demonstrate adequate as defined below (all screening labs should be performed within 14 days of treatment initiation):

    • Hematology

      • White Blood Count (WBC) ≥ 2 K/µL
      • Platelet count ≥ 100 K/µL
      • Absolute Neutrophil Count ≥ 1.5 K/µL
      • Hemoglobin > 9.0 g/dL or ≥ 5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks)
    • Biochemistry

      • Serum creatinine ≤1.5 x institutional ULN OR Measured or calculated creatinine clearance ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN (Creatinine clearance should be calculated per institutional standard)
      • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤5 × ULN for participants with liver metastases)
      • Total bilirubin (TBILI) ≤ 1.5 x institutional ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level of < 3.0 x institutional ULN) OR Direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN)
  • Women of childbearing potential (WOCBP) must have a negative serum pregnancy within 72 hours prior to registration.
  • WOCBP who are sexually active must use highly effective methods of contraception during treatment and for 28 days after the last dose of paxalisib. For male subjects with a pregnant or non-pregnant WOCBP partner, contraception measures are required during treatment and for 28 days after the last dose of paxalisib.

The subject, in consultation with the investigator, will select the most appropriate method of contraception from the permitted list of contraception methods, and site personnel will instruct the subject in its consistent and correct use as needed.

In addition, the investigator will instruct the subject to notify the site immediately if pregnancy of the subject or their partner is known or suspected.

Highly effective methods of contraception are those that, alone or in combination, result in a failure rate of less than 1% per year when used consistently and correctly and include:

  • Established use of oral, injected, or implanted hormonal methods of contraception
  • Correctly placed intrauterine device (IUD) or intrauterine system (IUS)
  • Male condom or female condom used WITH a spermicide (i.e., foam, gel, film, cream)
  • Male sterilization with appropriately confirmed absence of sperm in the post-vasectomy ejaculate
  • Bilateral tubal ligation or bilateral salpingectomy

Exclusion Criteria:

  • Participants unable to undergo MRI brain.
  • Participants with active systemic disease.
  • Participants with uncontrolled intercurrent illness.
  • Participants with prior exposure to mTOR/PI3K inhibitors
  • Prior malignancy (or any other malignancy requiring active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, superficial bladder cancer or other cancer from which the subject has been disease free for ≥ 3 years.
  • Participants who have received prior systemic anti-cancer therapy including investigational agents or radiotherapy within 4 weeks OR 5 half-lives prior to dosing, whichever is shorter. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
  • Participants who have difficulty with or are unable to swallow oral medication or have significant gastrointestinal disease that would limit absorption of oral medication.
  • Known history of infection with HIV, prior history of PML or any active significant infection (eg, bacterial, viral, or fungal).
  • Known history of hypersensitivity or anaphylaxis to paxalisib including active product or excipient components.
  • Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer which may have an effect of the metabolism of paxalisib.
  • Participants with uncontrolled medical comorbidities per investigator discretion including but not limited to interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, pre-exisiting Crohn's disease or ulcerative colitis or pre-existing chronic condition resulting in baseline grade 2 or higher diarrhea.
  • Participants with type I diabetes mellitus, participants with uncontrolled type II diabetes mellitus,despite being on oral anti-diabetic medication. , participants with Type II diabetes mellitus that are well controlled on insulin . Uncontrolled diabetes is defined as HbA1c >9% in addition to fasting glucose>140mg/dL on at least 2 occasions within 14 days prior to registration
  • Participants with uncontrolled hypertension despite optimal medical management (per investigator's assessment).
  • Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative polymerase chain reaction (PCR) and must be willing to undergo DNA PCR testing during the study to be eligible. Those who are HBsAg positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result to be eligible. Those who are hepatitis C PCR positive will be excluded.
  • Breast feeding or pregnant
  • Concurrent participation in another therapeutic trial.

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 identifier (NCT number): NCT04906096

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Contact: Lakshmi Nayak, MD (617) 632-2166

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United States, Massachusetts
Brigham and Women's Hospital Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Lakshmi Nayak, MD         
Principal Investigator: Lakshmi Nayak, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Lakshmi Nayak, MD    617-632-2166   
Sponsors and Collaborators
Lakshmi Nayak
Kazia Therapeutics Limited
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Principal Investigator: Lakshmi Nayak, MD Dana-Farber Cancer Institute
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Responsible Party: Lakshmi Nayak, Sponsor Investigator, Dana-Farber Cancer Institute Identifier: NCT04906096    
Other Study ID Numbers: 21-109
First Posted: May 28, 2021    Key Record Dates
Last Update Posted: July 12, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on only as required by federal regulation or as a condition of awards and agreements supporting the research.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data can be shared no earlier than 1 year following the date of publication
Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at

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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 Lakshmi Nayak, Dana-Farber Cancer Institute:
Primary Central Nervous System Lymphoma
Non-Hodgkin Lymphoma of Extranodal Site
Additional relevant MeSH terms:
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Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action