A Study to Assess the Safety, Tolerability and Anti-tumour Activity of Ascending Doses of Selumet… (NCT02586987) | Clinical Trial Compass
CompletedPhase 1
A Study to Assess the Safety, Tolerability and Anti-tumour Activity of Ascending Doses of Selumetinib in Combination With MEDI4736 and Selumetinib in Combination With MEDI4736 and Tremelimumab in Patients With Advanced Solid Tumours
United States58 participantsStarted 2015-12-28
Plain-language summary
This is a Phase I, open-label, multi-centre, drug combination study of double and triple combination oral selumetinib (AZD6244 Hyd-sulfate) plus intravenous (IV) MEDI4736 and oral selumetinib plus IV MEDI4736 and IV tremelimumab in patients with advanced solid tumours.
Who can participate
Age range18 Years – 99 Years
SexALL
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Inclusion criteria
✓. Written informed consent and any locally-required authorization (eg, Health Insurance Portability and Accountability Act in the US, EU Data Privacy Directive in the EU) obtained from the patient prior to performing any protocol-related procedures, including pre-screening and screening evaluations
✓. Age ≥18 years at time of study entry
✓. Histological or cytological confirmation of locally advanced (stage IIIB) or metastatic (stage IV) solid tumours refractory to standard therapy or for which no standard therapy exists
✓. World Health Organisation Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks
✓. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated assessment as per Response Evaluation Criteria in Solid Tumours (RECIST criteria v1.1)
✓. Female patients and males with partners of childbearing potential should be using highly effective contraceptive measures. Females should not be breastfeeding and must have a negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-childbearing potential by fulfilling 1 of the criteria below at screening.
✓. Male patients should be willing to use barrier contraception ie, condoms plus spermicide
✓. Mandatory provision of tumour tissue sample available at study entry for exploratory biomarker research. Cytology samples for this exploratory biomarker research will not be acceptable
Exclusion criteria
What they're measuring
1
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Adverse Events
Timeframe: From screening until approximately 30 days after last dose of study drug at disease progression
2
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of safety laboratory tests
Timeframe: From screening until approximately 30 days after last dose of study drug at disease progression
3
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of blood pressure (BP)
Timeframe: From screening until approximately 30 days after last dose of study drug at disease progression
4
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Electrocardiogram (ECG)
Timeframe: From screening until approximately 30 days after last dose of study drug at disease progression
5
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of physical examinations
Timeframe: From screening until approximately 30 days after last dose of study drug at disease progression
6
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Echocardiogram (ECHO)
✕. Any unresolved toxicity NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
✕. History of leptomeningeal carcinomatosis and brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have a CT / MRI of the brain prior to study entry
✕. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], celiac disease, irritable bowel disease, or other serious GI (Gastrointestinal) chronic conditions associated with diarrhoea, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[eg, granulomatosis with polyangiitis, Graves' disease; rheumatoid arthritis, hypophysitis, uveitis\]) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
✕. History of active primary immunodeficiency
✕. Current or prior use of immunosuppressive medication within 14 days before the 1st dose of MEDI4736. The following are exceptions to this criterion:
✕. As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant, active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol or active infection including hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) or known history of clinical diagnosis of tuberculosis
Timeframe: From screening until approximately 30 days after last dose of study drug at disease progression
7
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of pulse
Timeframe: From screening until approximately 30 days after last dose of study drug at disease progression
8
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of body temperature
Timeframe: From screening until approximately 30 days after last dose of study drug at disease progression
9
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of respiratory rate
Timeframe: From screening until approximately 30 days after last dose of study drug at disease progression
10
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Multigated Acquisition (MUGA)
Timeframe: From screening until approximately 30 days after last dose of study drug at disease progression
11
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Ophthalmic examination (best corrected visual acuity)
Timeframe: From screening until approximately 30 days after last dose of study drug at disease progression
12
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Ophthalmic examination (Intraocular pressure)
Timeframe: From screening until approximately 30 days after last dose of study drug at disease progression
13
Safety and tolerability of Selumetinib in combination with MEDI4736, and in combination with MEDI4736+ tremelimumab by assessment of Ophthalmic examination (slit lamp fundoscopy)
Timeframe: From screening until approximately 30 days after last dose of study drug at disease progression