Paxalisib (GDC-0084) In Recurrent Or Refractory PCNSL

NCT04906096 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 21-109
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Primary Central Nervous System Lymphoma; Non-Hodgkin Lymphoma of Extranodal Site

Keywords

Primary Central Nervous System Lymphoma; Non-Hodgkin Lymphoma of Extranodal Site

Outcome Measures

Primary Outcomes (1)

• Number of participants with Objective Response Rate (ORR)

  The Objective Response (ORR) is defined as a complete, unconfirmed complete or partial response as determined by the investigator assessment using IPCG criteria

  Up to 24 Months

Secondary Outcomes (4)

• Number of participants with Durable Objective Response Rate (ORR)

  Up to 24 Months

• Overall Survival

  Up to 24 Months

• Progression Free Survival (PFS)

  up to 24 Months

• Number of cumulative treatment-emergent adverse events (TEAEs)

  up to 24 Months

Study Arms (1)

PAXALISIB

EXPERIMENTAL

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.

Drug: PAXALISIB

Interventions

PAXALISIB DRUG

Each study treatment cycle lasts 28 days, up to 24 months. Oral, daily, dosage per protocol

Also known as: GDC-0084

PAXALISIB

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lakshmi Nayak, MD: lead
• Kazia Therapeutics Limited: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Interventions

GDC-0084

Study Officials

• Lakshmi Nayak, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lakshmi Nayak, MD

CONTACT

(617) 632-2166; Lakshmi_Nayak@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: May 28, 2021
• Study Start: June 1, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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 innovation@dfci.harvard.edu

Locations

US (2)