Glioblastoma MultiformePhase 2NCT02850744

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

A Phase 2 study testing PQR309 in people with Glioblastoma Multiforme, run by PIQUR Therapeutics AG at 1 site in Switzerland.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Glioblastoma Multiforme
What is being tested?: PQR309
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: 1 siteSwitzerland
Study dates: Jul 2015to Nov 2017
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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
More than 4 weeks from any investigational agent (at the judgment of the investigator and in agreement with lead investigator and PIQUR)
Adequate hematological, liver and renal function defined as follows:
Absolute neutrophil count (ANC) ≥1.5x109/l, platelets ≥ 100x109/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
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

Who cannot join

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

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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,
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 urine or serum pregnancy test within 7 days prior to first dose of PQR309
Adequate contraception is defined as surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), or double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). Male patients must agree to use condoms as contraception method.
Child-bearing potential for the sake of this study is defined as sexually mature women who have not undergone a hysterectomy, have not been naturally postmenopausal for at least 12 consecutive months or have a serum FSH < 40 mIU/ml.

Trial locations and contacts

1 site in 1 country.

Switzerland1 site

University Hospital Zurich, Neurology
Zurich, 8091

Other trials in Switzerland

About this study

Official title: Open-label, Non-randomized, Two-stage Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamic Effects of PQR309 in Patients With Progressive Glioblastoma

Read the detailed description

Open-label, non-randomized, two-stage, multi-center study evaluating clinical efficacy, safety, pharmacokinetics and pharmacodynamic effects of PQR309 in patients with progressive glioblastoma during or after standard temozolomide chemoradiotherapy.

The first stage of the study will enroll a minimum of 18 patients with glioblastoma at first progression during or after temozolomide chemoradiotherapy or temozolomide only. Following the completion of recruitment of patients in the first stage of the study, the decision will be made by the study team (study investigators and the sponsor), based on the continuous evaluation of safety and efficacy data, whether to continue recruitment of patients in the second stage while awaiting the data analyses. 17 additional patients may be enrolled for the second stage of the study, for a minimum of 35 patients in total. All patients evaluable for the primary endpoint will be followed until disease progression or death.

Conditions: Glioblastoma Multiforme
Being tested: PQR309
Medical subject headings: Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PQR309Drug
Also called temozolomide
80mg capsules p.o. once daily and possibly Standard Treatment with temozolomide

Study groups in NCT02850744
Study group	Role	What they receive
Single-arm	Other	Open label, single arm including patients with progressive glioblastoma during or after temozolomide chemotherapy obtaining PQR309 80mg capsules. Receives: Drug: PQR309

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Measured: 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
Non surgical cohort
Measured: 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
Surgical cohort
Measured: 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
Surgical Cohort
Measured: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes in pulse rate
Non-surgical cohort
Measured: 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
Surgical cohort
Measured: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes in blood pressure
Non-surgical cohort
Measured: 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 body weight
Surgical cohort
Measured: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes in body weight
Non-surgical cohort
Measured: 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 temperature
Surgical Cohort
Measured: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes in temperature
Non-surgical cohort
Measured: 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 ECG
Surgical Cohort
Measured: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes in ECG
Non-surgical cohort
Measured: 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
Physical examination according to Karnofsky Performance Status
Surgical cohort
Measured: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Physical examination according to Karnofsky Performance Status
Non-surgical cohort
Measured: 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
Depression Test (PHQ-9)
Surgical cohort
Measured: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Depression test PHQ-9
Non-surgical cohort
Measured: CAssessment 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
Generalized Anxiety Disorder mood scale score (GAD7)
Surgical Cohort
Measured: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Generalized Anxiety Disorder mood scale score (GAD)
Non-surgical cohort
Measured: Cycle 1Assessment 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 routine blood chemistry
Surgical cohort
Measured: Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes in routine blood chemistry
Non-surgical cohort
Measured: Cycle 1 on day 1,8,15, Cycle 2 day 1& 15, Cycle 3 und follow up cycles on day 1 up to 24 weeks, end of treatment & 30 days after last treatment
Changes in hematology
Surgical cohort
Measured: Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes in hematology
Non-surgical cohort
Measured: Cycle 1 on day 1,8,15, Cycle 2 day 1& 15, Cycle 3 und follow up cycles on day 1 up to 24 weeks, end of treatment & 30 days after last treatment
Changes of urinalysis
Surgical cohort
Measured: Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes of urinalysis
Non-surgical cohort
Measured: Cycle 1 on day 1,8,15, Cycle 2 day 1& 15, Cycle 3 und follow up cycles on day 1 up to 24 weeks, end of treatment & 30 days after last treatment
Change of Insulin/Glucose/C-Peptide
Surgical cohort
Measured: Day 1: at pre-dose and 0.5, 1, 2, 4, 6, 8 hours post-dose (± 5 minutes) Day 2: at pre-dose (= 24 hour post first dose on Day 1) (± 5 minutes)& 3 - Pre-dose, and 1hr post dose. Day 4 - 24hr post last dose on Day 3
Change of Insulin/Glucose/C-Peptide
Non- surgical cohort
Measured: Cycle 1 Day 1 - Pre-dose, 1hr post dose. Day 2 - 24hr post-dose. Cycle 2 Day 1 - pre-dose.
Change of Haemostasis
Non- surgical cohort
Measured: Cycle 1 Day 1 - Pre-dose, 1hr post dose. Day 2 - 24hr post-dose. Cycle 2 Day 1 - pre-dose.
Change of Haemostasis
Surgical cohort
Measured: Cycle 1 Day 1 - Pre-dose, 1hr post dose. Day 2 - 24hr post-dose. Cycle 2 Day 1 pre-dose.
Determination of cmax
Surgical cohort
Measured: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the last dose
Determination of cmax
Surgical cohort
Measured: Day 1: at pre-dose and 0.5, 1, 2, 4, 6, 8 hours post-dose; Day 2: at pre-dose (= 24 hour post first dose on Day 1), Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose, Day 4: at 24h after the last dose
Determination of AUC0-24
Non-surgical cohort
Measured: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the last dose
Determination of AUC0-24
Non-surgical cohort
Measured: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the
Determination of tmax
Non-surgical cohort
Measured: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the
Determination of AUClast
Non-surgical cohort
Measured: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the
Determination of tmax
Surgical cohort
Measured: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the last dose
Determination of AUClast
Surgical cohort
Measured: Day 1: at pre-dose and 0.5, 1, 2, 4, 6, 8 hours post-dose; Day 2: at pre-dose (= 24 hour post first dose on Day 1), Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose, Day 4: at 24h after the last dose
Determination of AUC0-∞
Surgical cohort
Measured: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the last dose
Determination of AUC0-∞
Non-surgical cohort
Measured: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the
Determination of t½
Surgical cohort
Measured: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the last dose
Determination of t½
Non-surgical cohort
Measured: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the
Assessment of tumor concentration,
Surgical cohort only
Measured: On day of surgery (day 3)
Assessment of PQR309 concentration in cerebrospinal fluid Day 3,pre-dose,0.5h, 1h, 2h, 4h, 6h, 8h post-dose Day 4 24h after the last dose given
Surgical cohort only
Measured: On day of surgery (day 3)
Assessment of PQR309 Skin concentration
Surgical cohort only
Measured: On day of surgery (day 3)
Overall Response Rate (ORR) including complete and partial Response based on RANO criteria
Surgical and Non-surgical Cohort
Measured: 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
Duration of response (DOR) based on RANO criteria
Surgical and non-surgical cohort
Measured: 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 at 3 months (PFS3) based on RANO criteria
Surgical and non surgical cohort
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2015Nov 2017

First posted1 Aug 2016 (estimated)
Study startJul 2015
Primary completionNov 2017
Study completionNov 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02850744
Sponsor's protocol ID: PQR309-004
Status last verified: Oct 2018
First submitted: 24 Mar 2016
Last updated: 19 Oct 2018
Results posted: No
Data monitoring committee: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Glioma, Medulloblastoma

All Glioblastoma Multiforme trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Open-label, Non-randomized, Two-stage Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamic Effects of PQR309 in Patients With Progressive Glioblastoma
ClinicalTrials.gov ID: NCT02850744
Acronym / sponsor ID: PQR309-004
Conditions: Glioblastoma Multiforme
Phase: Phase 2
Study type: Interventional
Recruitment status: Terminated
Enrolment: 10 participants (actual)
Lead sponsor: PIQUR Therapeutics AGIndustry (pharma, biotech, devices)
Collaborators: University Hospital, Basel, Switzerland, Insel Gruppe AG, University Hospital Bern, University Hospital, Zürich
Study start: Jul 2015
Primary completion: Nov 2017 (actual)
Study completion: Nov 2017 (actual)
First posted: 1 Aug 2016 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Single-arm	Other	Drug: PQR309Open label, single arm including patients with progressive glioblastoma during or after temozolomide chemotherapy obtaining PQR309 80mg capsules.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (21 listed)

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:
Only for patients of the non-surgical cohort:

Key exclusion criteria (18 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PQR309Also: temozolomide80mg capsules p.o. once daily and possibly Standard Treatment with temozolomide	Drug	Single-arm

Primary outcome

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]
Time frame: 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
Non Surgical Cohort, Tumor response evaluation according to RANO criteria
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]
Time frame: 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
Surgical Cohort, Tumor response evaluation according to RANO criteria

46 secondary outcomes

Number of Adverse Events and Serious Adverse Events as related to the study medication
Time frame: 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
Time frame: 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
Time frame: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes in pulse rate
Time frame: 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
Time frame: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes in blood pressure
Time frame: 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 body weight
Time frame: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes in body weight
Time frame: 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 temperature
Time frame: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes in temperature
Time frame: 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 ECG
Time frame: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes in ECG
Time frame: 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
Physical examination according to Karnofsky Performance Status
Time frame: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Physical examination according to Karnofsky Performance Status
Time frame: 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
Depression Test (PHQ-9)
Time frame: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Depression test PHQ-9
Time frame: CAssessment 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
Generalized Anxiety Disorder mood scale score (GAD7)
Time frame: Assessment on Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Generalized Anxiety Disorder mood scale score (GAD)
Time frame: Cycle 1Assessment 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 routine blood chemistry
Time frame: Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes in routine blood chemistry
Time frame: Cycle 1 on day 1,8,15, Cycle 2 day 1& 15, Cycle 3 und follow up cycles on day 1 up to 24 weeks, end of treatment & 30 days after last treatment
Changes in hematology
Time frame: Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes in hematology
Time frame: Cycle 1 on day 1,8,15, Cycle 2 day 1& 15, Cycle 3 und follow up cycles on day 1 up to 24 weeks, end of treatment & 30 days after last treatment
Changes of urinalysis
Time frame: Day1,2 pre-surgery, Day 3 surgery and Day 4 post-surgery and 30 days after surgery
Changes of urinalysis
Time frame: Cycle 1 on day 1,8,15, Cycle 2 day 1& 15, Cycle 3 und follow up cycles on day 1 up to 24 weeks, end of treatment & 30 days after last treatment
Change of Insulin/Glucose/C-Peptide
Time frame: Day 1: at pre-dose and 0.5, 1, 2, 4, 6, 8 hours post-dose (± 5 minutes) Day 2: at pre-dose (= 24 hour post first dose on Day 1) (± 5 minutes)& 3 - Pre-dose, and 1hr post dose. Day 4 - 24hr post last dose on Day 3
Change of Insulin/Glucose/C-Peptide
Time frame: Cycle 1 Day 1 - Pre-dose, 1hr post dose. Day 2 - 24hr post-dose. Cycle 2 Day 1 - pre-dose.
Change of Haemostasis
Time frame: Cycle 1 Day 1 - Pre-dose, 1hr post dose. Day 2 - 24hr post-dose. Cycle 2 Day 1 - pre-dose.
Change of Haemostasis
Time frame: Cycle 1 Day 1 - Pre-dose, 1hr post dose. Day 2 - 24hr post-dose. Cycle 2 Day 1 pre-dose.
Determination of cmax
Time frame: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the last dose
Determination of cmax
Time frame: Day 1: at pre-dose and 0.5, 1, 2, 4, 6, 8 hours post-dose; Day 2: at pre-dose (= 24 hour post first dose on Day 1), Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose, Day 4: at 24h after the last dose
Determination of AUC0-24
Time frame: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the last dose
Determination of AUC0-24
Time frame: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the
Determination of tmax
Time frame: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the
Determination of AUClast
Time frame: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the
Determination of tmax
Time frame: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the last dose
Determination of AUClast
Time frame: Day 1: at pre-dose and 0.5, 1, 2, 4, 6, 8 hours post-dose; Day 2: at pre-dose (= 24 hour post first dose on Day 1), Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose, Day 4: at 24h after the last dose
Determination of AUC0-∞
Time frame: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the last dose
Determination of AUC0-∞
Time frame: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the
Determination of t½
Time frame: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the last dose
Determination of t½
Time frame: Day 1: at pre-dose ,0.5, 1, 2, 4, 6, 8 hours post-dose ;Day 2: at pre-dose (= 24 hour post first dose on Day 1);Day 3:at pre-dose, 0.5h, 1.0h, 2h, 4h, 6h, 8h post-dose; Day 4: at 24h after the

Results and safety

The study was stopped early. Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2018.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Michael Weller, Professor principal investigator

University Hospital Zurich, Neurology

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PQR309 in people with Glioblastoma Multiforme, run by PIQUR Therapeutics AG at 1 site in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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] (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02850744.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2018.