Phase 2 study evaluating efficacy and safety of PQR309 in patients with relapsed or refractory primary CNS lymphoma

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 50

Inclusion Criteria

1. = 18 years of age.
2. Patient with histologically/cytologically confirmed PCNSL at first progression.
3. Relapsed or refractory PCNSL demonstrated by cranial MRI.
4. Presence of at least one lesion of bi-dimensionally measurable disease on baseline MRI with a contrast-enhancing tumor of at least 1 cm (10 mm) in the longest diameter.
5. Maximum two prior systemic therapy regimens excluding myeloablative therapy at first relapse.
6. If receiving corticosteroids, patients must have been on a stable or decreasing dose of corticosteroids and no more than 8 mg dexamethasone (or equivalent) for at least 5 days prior to date of enrollment.
7. Karnofsky Performance Score (KPS) = 70%.
8. More than 4 weeks from any investigational agent (at the judgment of the investigator and in agreement with lead investigator and PIQUR).
9. Adequate haematological, liver and renal function defined as follows: absolute neutrophil count (ANC) = 1.5x10^9/l, platelets = 100x10^9/l, hemoglobin = 100g/L. Total bilirubin = 1.5 times the upper limit of normal (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 times ULN. Serum Creatinine = 1.5 times ULN.
10. Able and willing to swallow and retain oral medication.
11. Female and male patients of reproductive potential must agree to use effective contraception from screening until 90 days after discontinuing study treatment.
12. Willing and able to sign the informed consent and to comply with the protocol for the duration of the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 34

Exclusion Criteria

1. Secondary CNS lymphoma or chronic immunosuppresion-associated CNS lymphoma.
2. Previous allogeneic hematopoietic stem cell transplant (HSCT transplant).
3. Patients with persisting symptoms from previous whole brain radiotherapy (WBRT).
4. Other concomitant anti-tumor therapy as determined by the study team.
5. Patients unable to undergo contrast-enhanced MRI.
6. Prior treatment with a PI3K inhibitor, AKT inhibitor, or mTOR inhibitor.
7. Patient is currently using herbal preparations or medications. Patient should stop using herbal medications 7 days prior to the first dose of the study drug.
8. Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others), or patients with active severe personality disorders.
9. Anxiety =CTC AE grade 3.
10. Patient has an uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, known HIV infection, chronic liver disease, chronic renal disease, pancreatitis, chronic pulmonary disease, active cardiac disease or cardiac dysfunction, interstitial lung disease, active autoimmune disease, uncontrolled diabetes, neuropsychiatric or social situations that would limit compliance with the study requirements.
11. Presence of gastrointestinal disease or any other condition that could interfere significantly with the absorption of the study drug.
12. Concomitant treatment with medicinal products that increase the pH (reduce acidity) of the upper gastrointestinal tract, including, but not limited to, proton-pump inhibitors (e.g. omeprazole), H2-antagonists (e.g. ranitidine) and antacids is restricted. Patients may be enrolled in the study after a washout period sufficient to terminate their effect. Patients who require treatment to increase the pH of the upper GI tract can be treated with 300mg ranitidine given once daily at bed-time. Importantly, in this case PQR309 dosing is switched to the early evening. Patients will take PQR309 on an empty stomach approx 4 hours after lunch and remain fasted for an additional 2 hours prior to the evening meal.
13. Patient has a history of invasive malignancy other than PCNSL. Patients are eligible if they are disease free for at least 3 years and deemed to be at low risk for recurrence by the Investigator. Patients diagnosed with cervical cancer in situ, basal cell or squamous cell carcinoma of the skin and treated within the past 3 years are eligible.
14. Women who are pregnant or breast feeding.
15. Women able to conceive and unwilling to practice an effective method of birth control from screening until 90 days after discontinuing study treatment (women of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose of PQR309).
16. Fasting glucose > 7.0 mmol/L (126 mg/dL).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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