Open-label, Non-randomized, Phase 2 Study Evaluating Efficacy and Safety of PQR309 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- PQR309
- Conditions
- Primary Central Nervous System Lymphoma
- Sponsor
- PIQUR Therapeutics AG
- Locations
- 4
- Primary Endpoint
- Overall Response Rate
- Status
- Withdrawn
- Last Updated
- 7 years ago
Overview
Brief Summary
An open-label, non-randomized, two-stage, multicenter study evaluating clinical efficacy, safety and pharmacokinetics of PQR309 in patients with relapsed or refractory Primary Central Nervous System Lymphoma (PCNSL).
Detailed Description
An open-label, non-randomized, two-stage, multicenter study evaluating clinical efficacy, safety, and pharmacokinetics effects of PQR309 in patients with relapsed or refractory Primary Central Nervous System Lymphoma (PCNSL). The first stage of the study will enroll a minimum of 12 patients with relapsed or refractory Primary Central Nervous System Lymphoma (PCNSL) evaluable for the primary study objective. If during the first stage of the study data emerge that 80 mg p.o. qd is not adequately tolerated or is inefficacious in patients with relapsed or refractory Primary Central Nervous System Lymphoma (PCNSL), additional patients may be enrolled in the study to evaluate alternative dosing regimens, either a lower daily dose (eg. 60 mg) or a lower weekly dose with administration on 2 consecutive days followed by 5 days without treatment in 7-day treatment cycles (intermittent dosing schedule A).In all cases data from at least 12 evaluable patients will be required on the selected dosing regimen (daily or weekly) before the decision is made to proceed with this regimen into the second stage of the study.Nine (9) additional patients will be enrolled for the second stage of the study, for a minimum of 21 patients on the selected dosing regimen in total, evaluable for the final primary endpoint analysis.All patients evaluable for the primary endpoint will be followed until disease progression or death. Secondary objectives, PQR309 treatment safety and pharmacokinetics (PK) will be evaluated in all enrolled patients in both study stages.
Investigators
Eligibility Criteria
Inclusion Criteria
- •≥18 years of age.
- •Patient with histologically/cytologically confirmed Primary Central Nervous System Lymphoma (PCNSL)
- •Relapsed or refractory Primary Central Nervous System Lymphoma (PCNSL) demonstrated by cranial MRI.
- •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.
- •Maximum one prior systemic therapy regimen.
- •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.
- •Karnofsky Performance Score (KPS) ≥ 70%.
- •More than 4 weeks from any investigational agent.
- •Adequate haematological, liver and renal function
Exclusion Criteria
- •Central Nervous System (CNS) Lymphoma or chronic immunosuppression-associated central nervous system (CNS) lymphoma.
- •Previous allogeneic hematopoietic stem cell transplant (HSCT transplant).
- •Previous whole brain radiotherapy (WBRT)
- •Other concomitant anti-tumor therapy as determined by the study team.
- •Patients unable to undergo contrast-enhanced MRI.
- •Prior treatment with a phosphoinositide -3 kinase (PI3K) inhibitor, Protein Kinase B Inhibitor is known as AKT inhibitor, or mammalian target of rapamycin (mTOR) inhibitor.
- •Patient taking enzyme-inducing anti-epileptic drug (EIAED) \< 7 days of the first dose of PQR
- •Patient is taking a drug with a risk to promote QT prolongation and Torsades de Pointes.
- •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.
- •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.
Arms & Interventions
PQR309
A single arm study with PQR309, a phosphoinositide-3-kinases (PI3K) and inhibitor of the mammalian target of rapamycin (mTOR), 60mg/80mg given once a day, orally.
Intervention: PQR309
Outcomes
Primary Outcomes
Overall Response Rate
Time Frame: Every 8 weeks up to 6 months
ORR (Overall Response Rate) including complete response (CR), unconfirmed complete (CRu) and partial response (PR) according to the 2005 Response Criteria of the International Primary CNS Lymphoma Collaborative Group (IPCG) \[1\].
Secondary Outcomes
- Changes in puls rate(Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15 and 22, Day 43 and every subsequent 3 weeks up to 1 year, at the end of treatment and 30 days after last dose)
- Changes in blood pressure(Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15 and 22, Day 43 and every subsequent 3 weeks up to 1 year, at the end of treatment and 30 days after last dose)
- Changes in haematology(Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15,Day 22, Day 36 and Day 43 and every subsequent 3 weeks up to 1 year, at the end of treatment and 30 days after last dose)
- Changes of haemostasis(Week 1 Day 1 prior to treatment, Treatment on Day 22, Day 43 and every subsequent 3 weeks)
- Changes in temperature(Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15 and 22, Day 43 and every subsequent 3 weeks up to 1 year, at the end of treatment and 30 days after last dose)
- Physical examination according to Karnofsky Performance Status (KPS)(Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15 and 22, Day 43 and every subsequent 3 weeks up to 1 year, at the end of treatment and 30 days after last dose)
- Changes in routine blood chemistry(Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15, Day 22, Day 36 and Day 43 and every subsequent 3 weeks up to 1 year, at the end of treatment and 30 days after last dose)
- Changes of Insulin/Glucose/ C-peptide(Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15 and 22, Day 36, Day 43 and every subsequent 3 weeks up to 1 year, at the end of treatment and 30 days after last dose)
- Changes of ECG(Week 1 Day 1 prior to treatment, Treatment on Day 22, Day 43 and every subsequent 3 weeks up to 1 year)
- Number of Adverse Events as related to the study medication(Week 1 Day 1 to 30 days after last dose up to 12 months)
- Depression Test PHQ-9(Treatment Day 22, Day 43 and every subsequent 3 weeks later up to 1 year, at the end of treatment)
- Changes in body weight(Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15 and 22, Day 43 and every subsequent 3 weeks up to 1 year, at the end of treatment and 30 days after last dose)
- Generalized anxiety disorder mood scale score (GAD7)(Treatment Day 22, Day 43 and every subsequent 3 weeks later up to 1 year, at the end of treatment)
- Changes of urinanalysis(Week 1 Day 1 prior to treatment, Treatment on Day 22, Day 43 and every subsequent 3 weeks up to 1 year)