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PQR309 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma

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ClinicalTrials.gov Identifier: NCT02669511
Recruitment Status : Completed
First Posted : February 1, 2016
Last Update Posted : May 9, 2018
Sponsor:
Information provided by (Responsible Party):
PIQUR Therapeutics AG

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).

Condition or disease Intervention/treatment Phase
Primary Central Nervous System Lymphoma Drug: PQR309 Phase 2

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 : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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 Start Date : November 2015
Actual Primary Completion Date : April 2018
Actual Study Completion Date : April 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
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.
Drug: PQR309
Oral PQR309, 80mg or 60mg daily or intermittent dosing




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. ≥18 years of age.
  2. Patient with histologically/cytologically confirmed Primary Central Nervous System Lymphoma (PCNSL)
  3. Relapsed or refractory Primary Central Nervous System Lymphoma (PCNSL) demonstrated by cranial MRI.
  4. Presence of at least one lesion of bi-dimensionally measurable disease on baseline
  5. MRI with a contrast-enhancing tumor of at least 1 cm (10 mm) in the longest diameter.
  6. Maximum one prior systemic therapy regimen.
  7. 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.
  8. Karnofsky Performance Score (KPS) ≥ 70%.
  9. More than 4 weeks from any investigational agent.
  10. Adequate haematological, liver and renal function
  11. Able and willing to swallow and retain oral medication.
  12. Female and male patients of reproductive potential must agree to use effective contraception from screening until 90 days after discontinuing study treatment.
  13. Willing and able to sign the informed consent and to comply with the protocol for the duration of the study.

Exclusion Criteria:

  1. Central Nervous System (CNS) Lymphoma or chronic immunosuppression-associated central nervous system (CNS) lymphoma.
  2. Previous allogeneic hematopoietic stem cell transplant (HSCT transplant).
  3. 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 phosphoinositide -3 kinase (PI3K) inhibitor, Protein Kinase B Inhibitor is known as AKT inhibitor, or mammalian target of rapamycin (mTOR) inhibitor.
  7. Patient taking enzyme-inducing anti-epileptic drug (EIAED) < 7 days of the first dose of PQR309.
  8. Patient is taking a drug with a risk to promote QT prolongation and Torsades de Pointes.
  9. 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.
  10. 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.
  11. Anxiety ≥ Common Terminology Criteria (CTC) of adverse events (AE) grade 3.
  12. 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.

  13. Presence of gastrointestinal disease or any other condition that could interfere significantly with the absorption of the study drug.
  14. 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.
  15. 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.
  16. Women who are pregnant or breast feeding.
  17. 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).
  18. Fasting glucose > 7.0 mmol/L (126 mg/dL). or HbA1c > 6.4%.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02669511


Locations
United States, California
UC Irvine - Medical Center
Orange, California, United States, 92686
Kaiser Permanente-Sacramento
Redwood Estates, California, United States, 94063
Kaiser Permanente-Sacramento
Sacramento, California, United States, 95825
Germany
University Hospital Freiburg General Medicine I
Freiburg im Breisgau, Baden Würtenberg, Germany, 79106
Medizinische Klinik und Poliklinik III
Munich, Bavaria, Germany, 81377
Charite Universitaetsmedizin Berlin
Berlin, Germany
Neurologische University Hospital Bochum
Bochum, Germany, 44892
Klinik für Hämatologie, Onkologie und Palliativmedizin
Stuttgart, Germany, 70174
Switzerland
University Hospital Zurich, Neurology
Zurich, Switzerland, 8091
Sponsors and Collaborators
PIQUR Therapeutics AG
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

Responsible Party: PIQUR Therapeutics AG
ClinicalTrials.gov Identifier: NCT02669511     History of Changes
Other Study ID Numbers: PQR309-005
First Posted: February 1, 2016    Key Record Dates
Last Update Posted: May 9, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by PIQUR Therapeutics AG:
DLBCL

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases