A Clinical Trial to Evaluate AZD7648 Alone and in Combination With Other Anti-cancer Agents in Patients With Advanced Cancers.

  • STATUS
    Recruiting
  • End date
    Feb 26, 2024
  • participants needed
    186
  • sponsor
    AstraZeneca
Updated on 11 December 2021
oophorectomy
antineoplastic

Summary

This is a modular Phase I/IIa, open-label, multi-centre, study of AZD7648 administered orally, either as a monotherapy, or in combination with either cytotoxic chemotherapies or novel anti-cancer agents in participants with advanced malignancies.

Description

The modular design allows for an escalation of the dose of AZD7648 alone or in combination with either cytotoxic chemotherapies or novel anti-cancer agents, with intensive safety monitoring to ensure the safety of the participants.

The study consists of 2 modules each evaluating the safety and tolerability of AZD7648 monotherapy or with a specific combination partner.

Core module of the study is dose escalation (Part A) of AZD7648 monotherapy, administered orally, in participants with advanced solid tumours.

Combination module 1 has 2 study parts: Part A consisting of dose escalation cohorts and Part B, a safety and proof of concept Phase IIa expansion. A Safety Review Committee will review evaluable participants at each cohort and assess if the study should progress to Part B.

Details
Condition Advanced Malignancies
Treatment olaparib, Pegylated Liposomal Doxorubicin (PLD), PLD, AZD7648
Clinical Study IdentifierNCT03907969
SponsorAstraZeneca
Last Modified on11 December 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Capable and willing to give signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF)
Participant must be at least 18 years of age, at the time of signing the ICF
Participants must have histological or cytological confirmation of advanced malignancy considered to be suitable for study treatment
Eastern cooperative oncology group performance status 0-1
Life expectancy greater than 12 weeks
Progressive cancer at the time of study entry
Pharmacodynamics expansion cohorts: Participants must have at least 1 tumour suitable for biopsy and consent to having biopsies collected
Negative pregnancy test (urine or serum) prior to start of dosing for women of childbearing potential
Female participants must be post-menopausal, surgically sterile, or using an acceptable method of contraception 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
For the duration of the study (from the time they sign consent) and for 12 weeks after the last dose of study treatment, sexually active male participants must be willing to use contraception
Post-menopausal is defined as
No menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the post-menopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy). However in the absence of 12 months of amenorrhea, a FSH measurement is insufficient
Radiation-induced oophorectomy with last menses greater than 12 months ago
Chemotherapy-induced menopause with greater than 12 month interval since last menses
Surgical sterilisation

Exclusion Criteria

Any unresolved toxicities from prior therapy common terminology criteria for adverse event (CTCAE) Grade 2 (with the exception of alopecia)
Spinal cord compression or brain metastases unless definitively treated, asymptomatic, stable and not requiring steroids for at least 4 weeks
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 participant with active
hepatitis B, hepatitis C or human immunodeficiency virus
\. 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 curatively treated with no evidence of
disease for 5 years
\. 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
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: including small
molecule investigational products: 3 weeks or 5 half-lives (whichever is
longest), (c) Biological products including investigational immuno-oncology
agents: 4 weeks, (d) Radiation with a limited field for palliation: 1 week (3
months for radiation to the abdomen or pelvis), (e) Radiation to >30% of the
bone marrow or with a wide field: 4 weeks, (f) Lung radiation: 60 days, (g)
Major surgery: 4 weeks; minor surgery or biopsy: 1 week 7. During the 4 weeks
prednisone/day or equivalent for any reason. Ongoing low dose steroids for
prior to the first dose, receiving corticosteroids at a dose of >10 mg
longer than 3 months (excluding inhalational, nasal, creams, lotions, and
\. Receiving or having received concomitant medications, herbal supplements
gels) are not allowed
and/or foods known to significantly modulate CYP3A4 activity
\. Prior exposure to a deoxyribonucleic acid-pharmacokinetics inhibitor or
hypersensitivity to any excipient of the product
\. 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
Any of the following cardiac criteria
(a) Known reduced left ventricular ejection fraction below the institutional
lower limit of normal, (b) Mean resting corrected QT interval (QTc) >470
milliseconds obtained from 3 electrocardiograms in 24 hours using the
Fridericia formula, (c) Any factors that increase the risk of QTc prolongation
or arrhythmic events such as hypokalaemia, congenital long QT syndrome
immediate family history of long QT syndrome or unexplained sudden death under
years of age 12. Inadequate hematological or organ function 13. Involvement
in the planning and/or conduct of the study. 14. Judgement by the Investigator
that the participant should not participate in the study if the participant is
unlikely to comply with study procedures, restrictions and requirements
\. Previous enrolment in the present study. 16. For female participant only
currently pregnant or breast-feeding. 17. For food effect cohort only: insulin
dependent diabetes. 18\. History and/or presence of coronavirus disease 2019
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