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

Completed · Phase 1

Conditions studied: Lung Cancer, Melanoma, Head and Neck Carcinoma, Gastroesophageal Cancer, Breast Cancer, Pancreatic Adenocarcinoma, Colorectal Cancer, Biliary Tract Cancer

In brief

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.

Key facts

Study ID

NCT02586987

Run by

AstraZeneca

People needed

58

Starts

2015-12-28

Expected to finish

2019-09-20

Last updated by the study team

2019-11-18

Who can join

Age: 18 and older, up to 99. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• Postmenopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
• Women <50 years old would be considered postmenopausal if they have been amenorrheic for the past 12 months or more following cessation of exogenous hormonal treatments. The levels of luteinising hormone (LH) and follicle stimulating hormone (FSH) must also be in the postmenopausal range (as per the institution)
• Documentation of irreversible surgical sterilisation by hysterectomy and / or bilateral oophorectomy and/or bilateral salpingectomy but not tubal ligation
• 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
• Patients must have mCRC and, if MSI status is known, non-high MSI status. MSI status will be evaluated based on previous results of local MSI testing, if available. Patients with known MSI-high status will be excluded; patients with MSS, MSI-low, or unknown MSI status may be enrolled

You may not qualify if…

• Patients must not enter the study if any of the following exclusion criteria are fulfilled
• Previous enrolment in the present study
• Treatment with any of the following:
• Cytotoxic chemotherapy or other anticancer drugs within 28 days of the 1st dose of study treatment or any investigational agents within 5 half-lives of the product
• MEDI4736 or selumetinib in the present study (ie, dosing with MEDI4736 or selumetinib previously initiated in this study)
• Major surgical procedure, (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the 1st dose of study treatment, or have an anticipated need for major surgery during the study
• Palliative radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the 1st dose of study treatment
• Prior exposure to immune-mediated therapy, including, but not limited to, other anti-CTLA- 4 (Cytotoxic T-lymphocyte antigen-4), anti-PD-1 (Programmed cell death 1), anti-PD-L1 (Programmed cell death ligand 1), or anti-PD-L2 (Programmed cell death ligand 2) antibodies, including therapeutic anticancer vaccines
• Receipt of live attenuated vaccine within 30 days prior to the first dose of IP
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• 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
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis and may be included after consultation with the medical monitor
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with selumetinib, MEDI4736 or tremelimumab may be included after consultation with the medical monitor
• 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:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment
• 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:
• Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
• 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
• Screening for chronic conditions is not required
• Any of the following cardiac criteria:

Where it is running

• Research Site — Chicago, Illinois, United States
• Research Site — Boston, Massachusetts, United States
• Research Site — Las Vegas, Nevada, United States
• Research Site — New Brunswick, New Jersey, United States
• Research Site — Charlotte, North Carolina, United States
• Research Site — Pittsburgh, Pennsylvania, United States

Full record on ClinicalTrials.gov

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