Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamic Effects of PQR309 in Glioblastoma Patients

NCT02850744 | Terminated Phase 2

• 1 other identifier: PQR309-004
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

PQR309 is an oral, dual pan-PI3K (phosphatidylinositol 3-kinase phosphoinositide 3-kinase) and mTOR (mammilian target of rapamycin) inhibitor that penetrates the blood-brain barrier at pharmacodynamically active concentrations. This study plans to evaluate PQR309 in treatment of patients with first progression of glioblastoma.

Conditions

Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (2)

• Progression-free survival rate at 6 months (PFS6) based on RANO criteria [30]glioblastoma, using progression-free survival rate at 6 months (PFS6) based on RANO criteria [30]

  Non Surgical Cohort, Tumor response evaluation according to RANO criteria

  Change to base line of contrast MRI scans and incorporated clinical signs will be assessed on Day 1 of Cycle 1 and on Day 1 of every following cycle and at the end of treatment which can be up to 24 months after

• Progression-free survival rate at 6 months (PFS6) based on RANO criteria [30]glioblastoma, using progression-free survival rate at 6 months (PFS6) based on RANO criteria [30]

  Surgical Cohort, Tumor response evaluation according to RANO criteria

  Change to base line of contrast MRI scans and incorporated clinical signs will be assessed on Day1 pre-surgery, Day 4 post-surgery and 30 days after surgery and thereafter every 8 weeks (+/-7 days) until end of treatment up to 24mths

Secondary Outcomes (46)

• Number of Adverse Events and Serious Adverse Events as related to the study medication

  Cycle 1 on Day 1,2,8 and 15, on Cycle 2 and following cycles on Day 1 and 15 und 30 days after end of treatmen which can up to 24 months

• Number of Adverse Events and Serious Adverse Events as related to the study medication

  Assessment on Day 1,2 pre-surgery, Day3 surgery, Day4 post -surgery and 30 days after surgery, Cycle 2 on Day 1 and 15 and 30 days after end of treatment which can be up to 24 months

• Changes in pulse rate

  Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery

• Changes in pulse rate

  Assessment will during Cycle 1 on day 1,8,15, Cycle 2 day 1, Cycle 3 und follow up cycles on day 1 up to 24 weeks, end of treatment and 30 days after last treatment

• Changes in blood pressure

  Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery

Study Arms (1)

Single-arm

OTHER

Open label, single arm including patients with progressive glioblastoma during or after temozolomide chemotherapy obtaining PQR309 80mg capsules.

Drug: PQR309

Interventions

PQR309 DRUG

80mg capsules p.o. once daily and possibly Standard Treatment with temozolomide

Also known as: temozolomide

Single-arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed glioblastoma at first progression following or during standard temozolomide chemoradiotherapy (TMZ/RTTMZ)
• older than 18 years of age
• Radiographic demonstration of disease progression by RANO criteria
• Only for patients of the surgical cohort:
• Eligible for open resection of progressive tumor according to standard practice of the study center
• Availability of adequate surgical tissue sample for the evaluation of concentration of PQR309 in the tumor and its PD effect
• Patients treated with PQR309 after incomplete surgical resection may still have measurable disease according to RANO criteria and may therefore be evaluable for evaluation of response to treatment with PQR309 according to RANO criteria. The best response in patients treated with PQR309 after complete surgical resection is stable disease. All patients can be assessed for PFS6.
• Only for patients of the non-surgical cohort:
• \- Presence of at least one lesion of bi-dimensionally measurable disease by MRI with a contrast-enhancing tumor of at least 1 cm (10 mm) in the longest diameter on baseline MRI is required for patients who do not undergo surgery at relapse. For patients who undergo surgery for recurrence but do not participate in the presurgical PQR309 dosing cohort, the same rules regarding response assessment as in the surgical cohort apply. All patients can be assessed for PFS6.
• Patient must have at least 1 formalin-fixed paraffin-embedded archival tumor tissue block representative of glioblastoma available from the first surgical resection of glioblastoma.
• One prior systemic therapy regimen: patients must have received at least one dose of TMZ in the first line therapy. More than 6 cycles and alternative dosing regiments of TMZ are allowed.
• If receiving corticosteroids, patients must have been on a stable or decreasing dose of corticosteroids and no more than 8 mg dexamethasone equivalent for ≥ 5 days prior to baseline MRI.
• Karnofsky Performance Score (KPS) \>70%.
• More than 12 weeks from radiotherapy (RT)
• More than 4 weeks from last administration of TMZ

You may not qualify if:

• Second or later glioblastoma relapse
• Received more than one systemic treatment regimen for glioblastoma
• Patients receiving enzyme-inducing anti-epileptic drug (EIAED) within 7 days of the first dose of PQR309
• Patient is taking a drug with known 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
• Patients with glioblastoma known to contain IDH1 or 2 mutation
• Other concomitant anti-tumor therapy as determined by the study team
• Prior treatment with intracerebral agents, e.g. prolifeprospan 20 with carmustine wafer
• Patients unable to undergo contrast-enhanced MRI
• Fasting glucose \> 7.0 mmol/L or HbA1c \> 6.4%.
• 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 ≥CTC AE grade 3
• 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
• 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 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 wash-out period sufficient to terminate their effect (See section 11.2.2.8).Women who are pregnant or breast feeding,

Sponsors & Collaborators

• PIQUR Therapeutics AG: lead
• University Hospital, Basel, Switzerland: collaborator
• Insel Gruppe AG, University Hospital Bern: collaborator
• University Hospital, Zürich: collaborator

Study Sites (1)

University Hospital Zurich, Neurology

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michael Weller, Professor

  University Hospital Zurich, Neurology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2016
• First Posted: August 1, 2016
• Study Start: July 1, 2015
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: October 19, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)