None listed
Conditions
Brief summary
The primary purpose of this study is to evaluate the safety of a new cancer drug, ACT001. Part B will evaluate the combination treatment of ACT001 with pembrolizumab in patients with recurrent GBM (Glioblastoma Multiforme brain cancer) only. Who is it for? You may be eligible to participate in this study if you are aged 18 or over, and have been diagnosed with glioblastoma. Those who participated in Part A of the study (ACTRN12616000228482) may be eligible to also participate in this study, subject to principal investigator approval. Study details: Participants will receive oral ACT001 twice every day for 21 days, together with intravenous (IV) infusion of pembrolizumab on the first day. After 21 days, once the safety of this treatment is determined, all participants will be given the treatment in recurrent 21-day cycles until tumour progression or adverse event. Researchers will take a number of blood samples from the initial 3 participants in Day 1 of the first and second 21-day cycle, to examine the rate that the body processes the drug. MRI scans and assessments of treatment response will be taken before treatment and then every 9 weeks to look for changes in tumour growth. Participants will also be assessed for side effects throughout the study period. It is hoped that the findings of this trial will show whether the combination treatment of ACT001 with pembrolizumab can be safely given to cancer patients, and provide information on the rate of processing of ACT001 by the body when pembrolizumab is also given. Using this information, researchers hope to find if the combination of ACT001 and pembrolizumab is safe and effective.
Interventions
Part B will evaluate the combination treatment of ACT001 with pembrolizumab in patients with recurrent Glioblastoma Multiforme (GBM) only. 3 patients will be treated with ACT001 at a daily oral dose of 400mg in combination with pembrolizumab 200mg administered as an intravenous infusion on Day 1 of each 21-day cycle. Following completion of the first cycle of treatment for the first 3 patients, the SMC will assess the safety and tolerability of the combination treatment of ACT001 and pembrolizum
Part B will evaluate the combination treatment of ACT001 with pembrolizumab in patients with recurrent Glioblastoma Multiforme (GBM) only. 3 patients will be treated with ACT001 at a daily oral dose of 400mg in combination with pembrolizumab 200mg administered as an intravenous infusion on Day 1 of each 21-day cycle. Following completion of the first cycle of treatment for the first 3 patients, the SMC will assess the safety and tolerability of the combination treatment of ACT001 and pembrolizumab. If the Safety Monitoring Committee (SMC) assessment deems the combination of ACT001 and pembrolizumab safe and tolerable, 6 additional GBM patients will be enrolled and treated with the same ACT001 and pembrolizumab combination. Patients will continue treatment with ACT001 and pembrolizumab until tumor progression (assessed by Immunotherapy Response Assessment in Neuro-Oncology [iRANO]) or an adverse event requiring discontinuation from study treatment. A further 12 GBM patients may be enrolled in Part B of this study if at least 2 of the 9 patients treated with the ACT001+pembrolizumab combination experience a Partial Response or 6 of 9 patients experience Stable Disease or better. Alternatively, a decision may also be made to adjust the dose level or to implement patient selection based on biomarker data collected from the first nine patients in Part B. After progression, patients are assessed for a further 30 days. Remote patient assessment will continue to monitor overall survival up to 1 year following disease progression. Each time the IP is dispensed to a patient, received from the depot and / or returned or destroyed, the occurrence will be documented. This documentation indicates the amounts received from the depot, dispensed to the patient, and returned or destroyed, to ensure adherence to the study protocol treatment.
Sponsors
Accendatech AU Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed advanced or metastatic glioblastoma with no standard treatment options. 2. Patients with recurrent glioblastoma who satisfy all of the following may be enrolled: - Progressive tumor despite prior treatment with radiation therapy and temozolomide - Measurable disease by Response Assessment in Neuro-Oncology (RANO) criteria using gadolinium-enhanced MRI scanning - Either on no glucocorticoids or on a stable dose for 7 days prior to the first dose of study therapy that is equivalent to = 12.5 mg of prednisone daily - No evidence of intracranial hemorrhage (except for stable grade 1 hemorrhage), not receiving therapeutic anticoagulation or anti-platelet therapy, and have a normal INR and APTT - No radiation in the past 3 months 3. Male or female and at least 18 years of age. 4. Adequate organ function (ANC greater than or equal to 1.5 × 109 /L, lymphocytes greater than or equal to 0.5 × 109 /L, platelets greater than or equal to 75 × 109 /L, Hb greater than or equal to 10 g/dl; total bilirubin less than or equal to 1.5 × institutional upper limit of normal (ULN); ALT and AST less than or equal to 2.5 × ULN (less than or equal to 5.0 × ULN if liver metastasis); plasma creatinine less than or equal to 1.5 × ULN; QTc < 450 ms (male), < 470 ms (female). 5. A life expectancy of at least 12 weeks. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 7. Female subjects are eligible if they are of: a) Non-childbearing potential, defined as - Previous hysterectomy or bilateral oophorectomy - Previous bilateral tubal ligation - Post-menopausal (total cessation of menses for greater than or equal to 1 year) b) Childbearing potential with a negative serum pregnancy test at screening (within 7 days of the first investigational product administration), and uses adequate contraception before study entry and throughout the study until 28 days after the last investigational product administration. Adequate contraception, when used consistently and in accordance with both the product label and the instructions of the physician, are defined as follows: - Vasectomized partner who is sterile prior to the female patient’s enrolment and is her sole sexual partner - An intrauterine device with a documented failure rate of less than 1% per year - Double barrier contraception defined as condom with a female diaphragm 8. Male patients, if sexually active, must agree to use a highly-effective method of contraception (< 1% failure rate per year) with their female partners 9. Provided written informed consent prior to enrollment.
Exclusion criteria
- The patient has an uncontrolled infection. - The patient has serious diseases or stroke within 6 months prior to enrolment. - The patient has a gastrointestinal absorption disorder or cannot take oral drugs. - Uncontrolled brain metastases or spinal cord compression. Patients who were treated with surgical resection or radiation therapy at least 4 weeks earlier are eligible if they are neurologically stable, not taking glucocorticoids and have had an MRI scan performed within the previous 4 weeks showing no tumour progression. (GBM patients taking a steroid dose equivalent to 12.5mg of prednisone are eligible) - Pre-existing allergy to ACT001 or pembrolizumab or related compounds. - Treatment with other cancer therapies such as chemotherapy, biological or targeted therapy, immunotherapy or radiation therapy either currently or within 4 weeks of ACT001 dosing (6 weeks for BCNU, CCNU or mitomycin-C). Pembrolizumab is exempt from this exclusion in Part B - Unresolved toxicity from prior anti-tumour therapy. - Patients with active autoimmune diseases or history of autoimmune diseases except for patients with vitiligo or alopecia, or those with hypothyroidism following autoimmune thyroiditis on a stable replacement dose of thyroid hormone are not excluded. - Patients who have received chronic glucocorticoid treatment at levels above the equivalent of prednisone at > 12.5 mg/day or dexamethasone at > 2 mg/day, or other immunosuppressive medication within 14 days prior to the first dose of the study drug. - Major surgery within 30 days of commencing first study therapy. - Patients who have received organ transplantation - Pregnant or breast-feeding females. - A history of infection with HIV or hepatitis B or C viruses - The subject has participated in other drug clinical trials within 4 weeks prior to informed consent. - The subject is, in the opinion of the investigator, unsuitable for any reason.
Outcome results
None listed