25 Participants Needed

Paxalisib for Central Nervous System Lymphoma

Recruiting at 1 trial location
LN
Overseen ByLakshmi Nayak, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 1 JurisdictionThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot take strong CYP3A4 inhibitors or inducers, as they may affect the study drug. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the drug Paxalisib for central nervous system lymphoma?

While there is no direct data on Paxalisib for central nervous system lymphoma, similar treatments like ibrutinib have shown encouraging results, with a 58% response rate in trials for similar conditions. Additionally, targeting pathways like PI3-kinase, which Paxalisib affects, is being actively explored in clinical trials for related lymphomas.12345

How is the drug Paxalisib unique in treating central nervous system lymphoma?

Paxalisib is unique because it targets the PI3-kinase pathway, which is involved in the growth and survival of cancer cells, offering a novel approach compared to traditional treatments like high-dose methotrexate and whole-brain radiation therapy that have significant side effects.24678

Research Team

Lakshmi Nayak, MD - Dana-Farber Cancer ...

Lakshmi Nayak

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults with confirmed recurrent or refractory primary DLBCL CNS lymphoma, who have measurable disease on MRI and are stable after previous treatments, can join. They must be able to undergo MRI scans, have good organ function, use effective contraception if applicable, and not require high doses of steroids. Excluded are those with other active cancers or infections like HIV/Hepatitis B/C, allergy to Paxalisib components, uncontrolled illnesses or hypertension.

Inclusion Criteria

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
My MRI shows my disease is not responding to treatment and can be measured.
See 7 more

Exclusion Criteria

Concurrent participation in another therapeutic trial
My high blood pressure is not controlled despite taking medication.
I cannot swallow pills or have a stomach condition that affects medication absorption.
See 13 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Paxalisib (GDC-0084) in 28-day cycles for up to 24 months

24 months
Monthly visits for treatment and evaluations

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Paxalisib
Trial Overview The trial is testing the effectiveness of a drug called Paxalisib (GDC-0084) for treating primary central nervous system lymphoma that has come back or hasn't responded to treatment. Participants will receive this oral medication under study conditions to see how well it works against their cancer.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: PAXALISIBExperimental Treatment1 Intervention
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.

Paxalisib is already approved in United States for the following indications:

🇺🇸
Approved in United States as Paxalisib for:
  • None approved; Orphan Drug Designation for glioblastoma, diffuse intrinsic pontine glioma, and atypical teratoid/rhabdoid tumors

Find a Clinic Near You

Who Is Running the Clinical Trial?

Lakshmi Nayak

Lead Sponsor

Trials
1
Recruited
30+

Lakshmi Nayak, MD

Lead Sponsor

Trials
1
Recruited
30+

Kazia Therapeutics Limited

Industry Sponsor

Trials
12
Recruited
1,600+

Findings from Research

In a study of 85 patients with primary central nervous system lymphoma (PCNSL) treated with the R-MPV regimen, the treatment showed a high tumor control rate with 5-year progression-free and overall survival rates of 61.6% and 69.9%, respectively.
The CD79B Y196 mutation was identified as a significant predictive marker for a favorable response to R-MPV, indicating that patients with this mutation had prolonged survival, while this association was not seen in patients treated with high-dose methotrexate.
CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in primary central nervous system lymphoma.Yamaguchi, J., Ohka, F., Lushun, C., et al.[2023]
Ibrutinib showed promising efficacy in treating relapsed/refractory primary and secondary central nervous system lymphomas, with an objective response rate of 58% and a complete response rate of 55% among 33 patients studied.
The treatment resulted in a median progression-free survival of 3.1 months for primary CNS lymphoma and 10.2 months for secondary CNS lymphoma, with only one case of invasive fungal infection reported, indicating a favorable safety profile despite concurrent steroid use.
Ibrutinib for central nervous system lymphoma: the Australasian Lymphoma Alliance/MD Anderson Cancer Center experience.Lewis, KL., Chin, CK., Manos, K., et al.[2021]
In a study of 100 patients with primary central nervous system lymphoma, the combination of high-dose methotrexate and rituxan resulted in a higher complete remission rate (66% vs. 58%) compared to traditional treatment with high-dose methotrexate and whole brain radiotherapy.
The targeted treatment group also experienced significantly longer median progression-free survival (28 months) compared to the traditional treatment group (11 months), indicating that the methotrexate and rituxan combination is not only effective but also has fewer adverse reactions, making it a safer option, especially for elderly patients.
[Curative Efficacy of High Dose MTX Combined with Rituxan for Treatment Primary CNS Lymphoma].Mou, K., Gu, WW., Gu, CH., et al.[2018]

References

CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in primary central nervous system lymphoma. [2023]
Ibrutinib for central nervous system lymphoma: the Australasian Lymphoma Alliance/MD Anderson Cancer Center experience. [2021]
[Curative Efficacy of High Dose MTX Combined with Rituxan for Treatment Primary CNS Lymphoma]. [2018]
[Molecular pathogenesis and therapeutic development of primary central nervous system lymphoma: update and future perspectives]. [2022]
MYD88 L265P mutation and CDKN2A loss are early mutational events in primary central nervous system diffuse large B-cell lymphomas. [2022]
Primary Central Nervous System Lymphoma (PCNSL): Analysis of Treatment by Gamma Knife Radiosurgery and Chemotherapy in a Prospective, Observational Study. [2022]
Lymphomas of Central Nervous System. [2023]
Experience With Tirabrutinib in the Treatment of Primary Central Nervous System Lymphoma that Is Difficult to Treat With Standard Treatment. [2022]