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

• Register: ClinicalTrials.gov
• Last refreshed on: 14 March 2016
• Main ID: NCT02430363
• Date of registration: 23/04/2015
• Prospective Registration: No
• Primary sponsor: Medical Research Council
• Public title: Evaluation Of The Treatment Effectiveness Of Glioblastoma / Gliosarcoma Through The Suppression Of The PI3K/Akt Pathway In Compared With MK-3475
• Scientific title: Phase IIb Trial Evaluations Of The Effectiveness Of Treatment Glioblastoma / Gliosarcoma Through The Suppression Of The PI3K/Akt Pathway In Compared With MK-3475 (Pembrolizumab)
• Date of first enrolment: March 2013
• Target sample size: 58
• Recruitment status: Enrolling by invitation
• URL: https://clinicaltrials.gov/show/NCT02430363
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1/Phase 2

Countries of recruitment

Belgium, Germany, Italy, Poland, Russian Federation, Spain, Switzerland, Ukraine, United Kingdom, United States

Contacts

• Name: Jann Lee, PhD
• Affiliation: MRC Clinical Trials Unit

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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.

- Has inadequately controlled hypertension

- Has a history of hypertensive crisis or hypertensive encephalopathy

- Has had clinically significant cardiovascular disease within 12 months of start of
study drug

- Has a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to start of study drug.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Glioblastoma

Intervention(s)

Biological: Suppressor of the PI3K/Akt pathways

Drug: MK - 3475

Primary Outcome(s)

Progression Free Survival [Time Frame: Time Frame: 12 months]

Secondary Outcome(s)

Safety and tolerability of Pembrolizumab (Assessed by reported adverse events using CTCAE version 4.0) [Time Frame: Time Frame: 12 months]

Secondary ID(s)

ETIK-W/33-15

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

ECCO - the European CanCer Organisation

Department of Experimental Clinical Oncology, Aarhus University Hospital

Merck Sharp & Dohme Corp.

NCRI Clinical Studies Groups