- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02669511
PQR309 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma
Open-label, Non-randomized, Phase 2 Study Evaluating Efficacy and Safety of PQR309 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
- Able and willing to swallow and retain oral medication.
- Female and male patients of reproductive potential must agree to use effective contraception from screening until 90 days after discontinuing study treatment.
- Willing and able to sign the informed consent and to comply with the protocol for the duration of the study.
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 PQR309.
- 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.
- Anxiety ≥ Common Terminology Criteria (CTC) of adverse events (AE) grade 3.
Patient has an uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, 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.
- Presence of gastrointestinal disease or any other condition that could interfere significantly with the absorption of the study drug.
- Concomitant treatment with medicinal products that increase the potential hydrogen (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. Patients may be enrolled in the study after a washout period sufficient to terminate their effect.
- Patient has a history of invasive malignancy other than Primary Central Nervous System Lymphoma (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.
- Women who are pregnant or breast feeding.
- 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).
- Fasting glucose > 7.0 mmol/L (126 mg/dL). or HbA1c > 6.4%.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: 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.
|
Oral PQR309, 80mg or 60mg daily or intermittent dosing
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (ORR)
Time Frame: Every 8 weeks up to 6 months
|
ORR including complete response (CR, unconfirmed complete(CRu) and partial response (PR) according to the 2005 Response Criteria of the Central Nervous System (CNS) Lymphoma Collaborative Group (IPCG)
|
Every 8 weeks up to 6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of adverse events (AE) as related to the study medication.
Time Frame: Week 1 Day 1 to 30 days after last dose up to 12 months
|
Continous Dosing and Intermittent Dosing
|
Week 1 Day 1 to 30 days after last dose up to 12 months
|
Changes in puls rate
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 8,Day 15 and 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
|
Continous Dosing and Intermittent Dosing
|
Week 1 Day 1 prior to treatment, Treatment on Day 8,Day 15 and 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
|
Changes in blood pressure
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 8,Day 15 and 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
|
Continous Dosing and Intermittent Dosing
|
Week 1 Day 1 prior to treatment, Treatment on Day 8,Day 15 and 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
|
Changes in body weight
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 8,Day 15 and 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
|
Continous Dosing and Intermittent Dosing
|
Week 1 Day 1 prior to treatment, Treatment on Day 8,Day 15 and 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
|
Changes in temperature
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 8,Day 15 and 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
|
Continous Dosing and Intermittent Dosing
|
Week 1 Day 1 prior to treatment, Treatment on Day 8,Day 15 and 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
|
Changes in Physical examination according to Karnofsky Performance Status (KPS)
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 8,Day 15 and 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
|
Continous Dosing and Intermittent Dosing
|
Week 1 Day 1 prior to treatment, Treatment on Day 8,Day 15 and 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
|
Generalized anxiety disorder mood scale score (GAD7)
Time Frame: Treatment on Day 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
|
Continous Dosing and Intermittent Dosing
|
Treatment on Day 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
|
Depression Test PHQ-9
Time Frame: Treatment on 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
|
Continous Dosing and Intermittent Dosing
|
Treatment on 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
|
Changes in haematology
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15,Day 22, Day 36 and Day 43 and every subsequent 3 weeks, at the end of treatment and 30 days after last dose
|
Continous Dosing and Intermittent Dosing
|
Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15,Day 22, Day 36 and Day 43 and every subsequent 3 weeks, at the end of treatment and 30 days after last dose
|
Changes in Routine blood chemistry
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15,Day 22, Day 36 and Day 43 and every subsequent 3 weeks, at the end of treatment and 30 days after last dose
|
Continous Dosing and Intermittent Dosing
|
Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15,Day 22, Day 36 and Day 43 and every subsequent 3 weeks, at the end of treatment and 30 days after last dose
|
Changes of Insulin/Glucose/C-Peptide
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15,Day 22, Day 36 and Day 43 and every subsequent 3 weeks, at the end of treatment and 30 days after last dose
|
Continous Dosing and Intermittent Dosing
|
Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15,Day 22, Day 36 and Day 43 and every subsequent 3 weeks, at the end of treatment and 30 days after last dose
|
Changes of haemostasis
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 22 and Day 43 and every subsequent 3 weeks, at the end of treatment
|
Continous Dosing and Intermittent Dosing
|
Week 1 Day 1 prior to treatment, Treatment on Day 22 and Day 43 and every subsequent 3 weeks, at the end of treatment
|
Changes of urinanalysis
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 22 and Day 43 and every subsequent 3 weeks, at the end of treatment
|
Continous Dosing and Intermittent Dosing
|
Week 1 Day 1 prior to treatment, Treatment on Day 22 and Day 43 and every subsequent 3 weeks, at the end of treatment
|
Changes of ECG
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 22 and Day 43 and every subsequent 3 weeks, at the end of treatment
|
Continous Dosing and Intermittent Dosing
|
Week 1 Day 1 prior to treatment, Treatment on Day 22 and Day 43 and every subsequent 3 weeks, at the end of treatment
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Agnieszka Korfel, MD, Charite Universitaetsmedizin Berlin, Germany
- Principal Investigator: Uwe Schlegel, Prof, Neurologische UniversitätsklinikKnappschaftskrankenhaus Bochum GmbH
- Principal Investigator: Elisabeth Schorb, MD, UNIVERSITÄTSKLINIKUM FREIBURGKlinik für Innere Medizin I
- Principal Investigator: Martin Dreyling, Prof, Medizinische Klinik und Poliklinik III Klinikum der Universität München
- Principal Investigator: Gerald Illerhaus, Prof, Klinik für Hämatologie, Onkologie und PalliativmedizinStuttgart Cancer
- Principal Investigator: Michael Weller, Prof, University of Zurich
- Principal Investigator: Daniela Bota, MD, Center101 The City Drive SouthOrange, CA 92686
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- PQR309-005
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
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