Advanced Malignancies MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: AZD7648
Product Code: AZD7648
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not yet available
CAS Number: 2230820-11-6
Current Sponsor code: AZD7648
Other descriptive name
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Capable and willing to give signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 2 .Provision of signed and dated written genetic informed consent prior to collection of sample for exploratory genetic analysis (optional). 3. Patient must be at least 18 years of age, at the time of signing the ICF. Type of Patient and Disease Characteristics 4. Patients must have histological or cytological confirmation of advanced malignancy considered to be suitable for study treatment. 5. ECOG PS of 0 to 1. 6. Life expectancy greater than 12 weeks. 7 .Progressive cancer at the time of study entry. 8 .PD expansion cohorts (or PD expansion subgroup): Patients must have at least 1 tumour suitable for biopsy and consent to having biopsies collected. Reproduction 9. Negative pregnancy test (urine or serum) prior to start of dosing for women of childbearing potential (WOCBP). Women of child-bearing potential are defined as women between menarche and menopause who have not been permanently or surgically sterilised and are capable of procreation. 10. Female patients must be 1-year post-menopausal, surgically sterile, or using an acceptable method of contraception (acceptable methods of contraception are defined in Section 5.3.3) for the duration of the study (from the time they sign consent) and for 12 weeks after the last dose of study treatment to prevent pregnancy. 11. For the duration of the study and for 12 weeks after the last dose of study treatment, sexually active male patients must be willing to use contraception as is defined inSection 5.3.3. Post-menopausal is defined as: ?- Amenorrhoeic for 1 year of more following cessation of exogenous hormonal treatments. ?- Luteinising hormone and follicle stimulating hormone levels in the post-menopausal range for women under 50. ?- Radiation-induced oophorectomy with last menses greater than 1 year ago. ? -Chemotherapy-induced menopause with greater than 1-year interval since last menses ? -Surgical sterilisation (bilateral oophorectomy or hysterectomy) Module 1 and 2 specific criteria can be found in the relevant CSP modules. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 130 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Any unresolved toxicities from prior therapy CTCAE Grade =2 (with the exception of alopecia). 2. Spinal cord compression or brain metastases unless definitively treated (minimum of 3. weeks between completion of radiotherapy and first dose of study treatment and recovery from acute toxicity Grade =2), asymptomatic, stable)and not requiring steroids for at least 4 weeks. Disease outside the central nervous system must be present. 3.As judged by the Investigator, any evidence of severe or uncontrolled medical conditions including but not limited to: -Uncontrolled diabetes mellitus, uncontrolled seizures, active infection requiring systemic antibiotics, antifungal or antiviral drugs, severe chronic obstructive pulmonary disease, severe Parkinson’s disease, active inflammatory bowel disease, psychiatric condition, active bleeding diatheses, renal transplant, or active infection including any patient known to have hepatitis B, hepatitis C and human immunodeficiency virus. 4. Any other malignancy which has been active or treated within the past 3 years, with the exception of in situ cancer of the cervix, non-melanoma skin cancer, ductal carcinoma in situ, Stage 1 Grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for =5 years. 5. Refractory nausea and vomiting or unable to swallow and retain oral medication, chronic gastrointestinal diseases or previous bowel resection with clinically significant sequelae that would preclude adequate absorption of AZD7648, gastrointestinal symptoms CTCAE Grade >1, history of gastrointestinal ulceration and gastrointestinal haemorrhage within 6 months of first study drug administration. 6. Receiving or having received anti-cancer treatment within the following periods prior to the first dose of investigational product: (a) Cytotoxic treatment: 3 weeks (b) Non-cytotoxic drugs: 3 weeks or 5 half-lives (whichever is longest) (c) Small molecule investigational products: 3 weeks or 5 half-lives (whichever is longest) (d) Biological investigational products: 42 days (e) Radiation with a limited field for palliation: 1 week (3 months for radiation to the abdomen or pelvis) (f) Radiation to >30% of the bone marrow or with a wide field: 4 weeks (g) Lung radiation: 60 days (h) Major surgery: 4 weeks; minor surgery or biopsy: 1 week 7.During the 4 weeks prior to the first dose, receiving corticosteroids at a dose of >10 mg prednisone/day or equivalent for any reason. 8 .Receiving or having received concomitant medications, herbal supplements and/or foods known to significantly modulate CYP3A4 activity . The required washout period prior to starting study treatment is 3 weeks (5 weeks for enzalutamide or phenobarbital) until 28 days after the last dose of study treatment. Patients can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study if these were started at least 2 weeks prior to study treatment 9.Prior exposure to a DNA-PK inhibitor or hypersensitivity to any excipient of the product. 10.Cardiac dysfunction as defined by any of the following within 6 months of study entry: (a) Acute myocardial infarction (b) New York Heart Association Class II/III/IV heart failure (c) Unstable angina (d) Unstable cardiac arrhythmias eg, clinically important abnormalities in conduction or morphology of resting ECG such as complete left bundle branch block or third-degree heart bl
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: _Evaluate, efficacy, safety and tolerability of IMP _To investigate the safety and tolerability of AZD7648 when given orally to patients with advanced malignancies, as monotherapy and in combination with anticancer agents, and to define the doses and schedules for further clinical evaluation.;Secondary Objective: _To characterize the pharmacokinetics of AZD7648,following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. To characterize the effect of food on AZD7648 exposure(if conducted) _To understand the cytochrome P450 3A4 induction potential of AZD7648. _To obtain a preliminary assessment of anti-tumor activity of AZD7648 as monotherapy and in combination with anti-cancer agents.;Primary end point(s): _Adverse events (AEs)/serious adverse events (SAEs) _Dose-limiting toxicity (DLT) _Physical examination _Eastern Cooperative Oncology Group performance status (ECOG PS) _Vital signs _Electrocardiogram (ECG) and Echocardiogram (ECHO; combination module 1 only) _Laboratory data;Timepoint(s) of evaluation of this end point: According to schedule of activities. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Area under the curve (AUC) and/or AUC0-t after a single dose and AUCtau after multiple doses. Maximum plasma concentration (Cmax) after a single dose and Cmax,ss after multiple doses Time to reach maximum plasma concentration (tmax) Minimum plasma concentration at steady state (Cmin,ss) Half-life (t1/2) Accumulation ratio Dose proportionality AUC0-t and Cmax ratio for food effect Post-dose to pre-dose 4-ß-hydroxy cholesterol ratio Radiological response evaluated using response evaluation criteria in solid tumours (RECIST) 1.1 ? - Percentage best change in target lesion (TL) ? -Duration of response ? - Objective response rate (ORR) ? - Progression-free survival (PFS) -Overall Survival (Part B only);Timepoint(s) of evaluation of this end point: According to schedule of activities. | — |
Countries
France, Germany, Korea, Republic of, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed