800-872-2273

Clinical Trials and Studies

Your participation matters. Help us discover and cure!

Contact us at (800) USC-CARE (800-872-2273)

0C-14-10: A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD5363 under Adaptable Dosing Schedules in Patients with Advanced Solid Malignancies

Description

This is a phase I, open-label, multicentre study of AZD5363 administered orally in participants with advanced solid malignancies. AZD5363 is a novel, potent, selective inhibitor of the kinase activity of AKT (also known as protein kinase B). AZD5363 acts on cancers by blocking signalling through the AKT cellular survival pathway, leading to inhibition of cell proliferation and increased cell death. There are 6 parts to this study. USC will only take part in parts C, D, E and F. Parts C, D, E and F will investigate the tolerability and initial signs of anti-tumour activity of AZD5363 in tumour types that are considered most likely to be sensitive to AKT inhibition, as a result of bearing a mutation of PIK3CA, AKT1, PTEN or other molecular aberrations leading to dysregulation of the PI3K/AKT pathway. Part C will focus on tumours with a mutation of PIK3CA and will contain three separate cohorts Part D will focus on tumours with mutations of AKT1 or other molecular aberrations leading to dysregulation of the PI3K/AKT pathway, and will contain three separate cohorts Part E will focus on patients with advanced or metastatic ER positive breast tumours with mutations of AKT1 and will contain two separate cohorts. Part F will focus on patients with advanced or metastatic ER positive breast tumours with alterations of PTEN (restricted to genomic alterations which are predicted to ablate function of the gene, e.g. alterations with known functional significance and/or of most likely therapeutic significance. Each participant will receive AZD5363 as an intermittent regimen of 480 mg twice daily for 4 days on, 3 days off dosing Primary objective for Part C is to investigate the safety and tolerability of AZD5363 in participants with advanced or metastatic estrogen receptor positive (ER+) or human epidermal growth factor receptor 2 positive (HER2+) breast cancer, gynaecological (ovarian, cervical or endometrial) cancer, or other advanced solid cancer that has a PIK3CA mutation. Primary objective for Part D is to investigate the safety and tolerability of AZD5363 in patients with advanced or metastatic ER+ or HER2+ breast cancer, gynaecological (ovarian, cervical or endometrial) or other advanced solid cancer that has an AKT1 mutation or other molecular aberration leading to dysregulation of the PI3K/AKT pathway Primary objective for Part E is to investigate the safety and tolerability of AZD5363 in combination with fulvestrant in patients with advanced or metastatic ER positive breast cancer that has an AKT1 mutation. Primary objective for Part F is to investigate the safety and tolerability of AZD5363 in combination with fulvestrant in patients with advanced or metastatic ER+ positive breast cancer that has a PTEN mutation. Primary study endpoints for Parts C, D, E and F will be safety and tolerability.

Phase

N/A

Inclusion and Exclusion Criteria

  • Aged at least 18 years.
  • Parts A,B: The presence of a solid, malignant tumour, excluding lymphoma, that is resistance to standard therapies or for which no standard therapies exist.
  • ER+/HER2+ breast, ovarian, cervical, endometrial cancer, or other solid cancers, resistance to standard therapies with a PIK3CA gene mutation (Part C), AKT1 gene mutation (Part D) or a dysregulatory aberration on the PIK/AKT pathway (Part D), advanced or metastatic ER+ positive breast cancer that has an AKT1 gene mutation (Part E) or advanced or metastatic ER+ positive breast cancer that has a PTEN gene mutation (Part F).
  • The presence of at least one lesion that can be accurately assessed at baseline by CT, MRI or plain X-ray and is suitable for repeated assessment. Estimated life expectancy of more than 12 weeks.
  • Estimated life expectancy of more than 12 weeks.

  • Clinically significant abnormalities of glucose metabolism.
  • Spinal cord compression or brain metastases unless asymptomatic, treated and stable (not requiring steroids).
  • Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and HIV.
  • Evidence of clinically significant cardiac abnormalities, uncontrolled hypotension, left ventricular ejection fraction below the lower limit of normal for the site or experience of significant cardiac interventional procedures.
  • A bad reaction to AZD5363 or any drugs similar to it in structure or class.

Sites

Please contact Judy Lam-Tran to learn more about where you can participate in this trial. Please use the contact form on the right side.

Powered by SC CTSI