Evaluation Of The Treatment Effectiveness Of Glioblastoma / Gliosarcoma Through The Suppression Of The PI3K/Akt Pathway In Compared With MK-3475

Status unconfirmed · Phase 1/Phase 2

Conditions studied: Glioblastoma

In brief

It is known that after application of MK-3475 activated PD -1 negatively regulates the activation of T cells through suppression of the path of PI3K / Akt. This study will identify the effectiveness of oral inhibitors of PI3K / Akt pathway in comparison with MK-3475 (pembrolizumab).

Key facts

Study ID: NCT02430363
Run by: Medical Research Council
People needed: 58
Starts: 2013-03-01
Expected to finish: 2018-06-01
Last updated by the study team: 2016-02-24

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Have histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma). Participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made.
Previous first line therapy with at least radiotherapy and temozolomide
Be at first or second relapse.
Participants must have shown unequivocal evidence for tumor progression by MRI or CT scan.
CT or MRI within 14 days prior to start of study drug.
An interval of at least 4 weeks (to start of study agent) between prior surgical resection or one week for stereotactic biopsy.
An interval of at least 12 weeks from the completion of radiation therapy to start of study drug unless there is a new area of enhancement consistent with recurrent tumor outside the radiation field or there is unequivocal histologic confirmation of tumor progression
Participants must have recovered to grade 0 or 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy (including but not limited to exceptions of alopecia, laboratory values listed per inclusion criteria, and lymphopenia which is common after therapy with temozolomide).
From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.
Payment of charitable contributions may be required

You may not qualify if…

Current or planned participation in a study of an investigational agent or using an investigational device.
Has a diagnosis of immunodeficiency.
Has tumor primarily localized to the brainstem or spinal cord.
Has presence of diffuse leptomeningeal disease or extracranial disease.
Has received systemic immunosuppressive treatments within 6 months of start of study drug
Requires treatment with high dose systemic corticosteroids defined as dexamethasone > 4 mg/day or bioequivalent for at least 3 consecutive days within 2 weeks of start of study drug.
Has received prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection or convection enhanced delivery.
Requires therapeutic anticoagulation with warfarin at baseline; patients must be off warfarin or warfarin-derivative anti-coagulants for at least 7 days prior to starting study drug; however, therapeutic or prophylactic therapy with low-molecular weight heparin is allowed.
Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug
Has evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan other than those that are grade ≤ 1 and either post-operative or stable on at least 2 consecutive MRI scans.
Has gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE Grade > 3 within 6 months of start of study drug.
Has a known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
Has an active infection requiring systemic therapy.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial
Has a known history of HIV
Has known active Hepatitis B or Hepatitis C
Has received a live vaccine within 30 days prior to the first dose of study drug.
Has a known hypersensitivity to any of the study therapy products.
Has received anti-angiogenic or anti-VEGF targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc)
Has a history of non-healing wounds or ulcers, or bone refractures within 3 months of fracture
Has a history of arterial thromboembolism within 12 months of start of study drug.

Where it is running

Dana-Farber Cancer Institute — Boston, Massachusetts, United States
M D Anderson Cancer Center — Houston, Texas, United States
UCL- Cliniques Universitaires Saint Luc — Brussels, Belgium
St Johannes Hospital — Duisburg, Germany
Spedali Civili di Brescia — Brescia, Italy
IRCCS San Raffaele — Milan, Italy
Lower-Silesian Oncology Centre — Wroclaw, Lower Silesian Voivodeship, Poland
Pavlov State Medical University — Saint Petersburg, Russia
Hospital Universitario Germans Trias I Pujol — Barcelona, Spain
Universitätsklinik für Frauenheilkunde — Bern, Switzerland
Regional Cancer Center — Dnipro, Ukraine
National Institute of Cancer — Kiev, Ukraine
Royal Victoria Hospital — Belfast, Ulster, United Kingdom

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.