AZD5363 in Patients With Advanced Solid Tumors Harboring AKT Mutations

NCT03310541 | Completed Phase 1 FDA Drug

• 1 other identifier: 17-322
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

This study will test the recommended dose of AZD5363 (recommended from a previous phase 1 study of the drug) in patients with specific AKT mutations. In patients who have ER positive breast cancer with an AKT mutation, they will also be receiving a standard breast cancer drug called fulvestrant that is given as an injection. In patients who have prostate cancer with an AKT mutation, they will also be receiving a standard prostate cancer drug called enzalutamide that is taken orally.

Conditions

Breast Cancer; Prostate Cancer; Advanced Solid Tumors

Keywords

AZD5363; AKT Mutations; 17-322

Outcome Measures

Primary Outcomes (1)

• number of patients with an objective response rate (ORR) of AZD5363

  A response is defined as any of the following: a response according to RECIST v 1.1, PCWG3 (for patients with measurable visceral and/or nodal disease at baseline) or RANO as applicable or a reduction in the PSA level of 50% or more (for prostate cancer patients without visceral and/or nodal disease at baseline), with a confirmatory assessment at least 4 weeks later.

  1 year

Study Arms (3)

Prostate, Previously treated with Enzalutamide

EXPERIMENTAL

28-DAY CYCLE AZD5363 400mg PO twice daily for 4 days on, 3 days off, every week + Enzalutamide 160 mg PO once daily

Drug: AZD5363; Drug: Enzalutamide

ER+ Breast, Previously treated with Fulvestrant

EXPERIMENTAL

28-DAY CYCLE AZD5363 400mg PO twice daily for 4 days on, 3 days off, every week + Fulvestrant 500mg IM days 1, 15, 29 (cycle 2 day 1) and then every 4 weeks

Drug: AZD5363; Drug: Fulvestrant

Advanced Solid Tumors

EXPERIMENTAL

28-DAY CYCLE AZD5363 480mg PO twice daily for 4 days on, 3 days off, every week

Drug: AZD5363

Interventions

AZD5363 DRUG

AZD5363 400mg PO twice daily for 4 days on, 3 days off, every week

Advanced Solid Tumors; ER+ Breast, Previously treated with Fulvestrant; Prostate, Previously treated with Enzalutamide

Enzalutamide DRUG

Enzalutamide 160 mg PO once daily

Prostate, Previously treated with Enzalutamide

Fulvestrant DRUG

500mg IM days 1, 15, 29 (cycle 2 day 1) and then every 4 weeks

ER+ Breast, Previously treated with Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed recurrent or metastatic advanced solid tumor, for which there is no curative-intent treatment option and confirmation of the presence of AKT1, AKT2, or AKT3 mutations detected by the MSK-IMPACT assay platform or other CLIA-approved test
• ER+ breast cancer patients must have received and progressed on Fulvestrant and be post-menopausal
• Prostate cancer patients must have received and progressed on enzalutamide
• Age ≥ 18 years
• ECOG performance status ≤ 2 with no deterioration over the previous 2 weeks
• Life expectancy of ≥ 12 weeks
• Measurable disease as defined by the tumor specific relevant response criteria for the breast and other solid tumor cohorts (measurable disease is not required for enrollment in the prostate cancer cohort):
• RECIST version 1.1 criteria
• Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria.
• RANO criteria
• Females should be using adequate contraceptive measures (see Section 0), should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
• Post-menopausal defined as:
• Aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
• Estradiol, FSH and LH levels in post-menopausal range while receiving LHRH analogues for medical castration in patients with breast cancer.
• Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.

You may not qualify if:

• ER+ breast cancer patients harboring the AKT1 E17K mutation (patient population tested in MSK IRB# 14-214, study D3610C00001 part E, ClinicalTrials.gov NCT01226316).
• Diabetes mellitus type 1
• Fasting plasma glucose \[fasting is defined as no calorific intake for at least 8 hours\]:
• ≥ 126 mg/dL for those patients without a pre-existing diagnosis of Type 2 diabetes mellitus
• ≥ 167mg/dL for those patients with a pre-existing diagnosis of Type 2 diabetes mellitus
• Glycosylated haemoglobin (HbA1C) ≥8.0%
• Requirement for insulin for routine diabetic management and control
• Requirement for \>2 oral hypoglycaemic medications for routine diabetic management and control
• Treatment with any of the following:
• Any investigational agents or study drugs from a previous clinical study within 30 days of the first dose of study treatment
• Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks or 5 half lives, whichever is longer, of the first dose of study treatment, except fulvestrant, enzalutamide or hormonal therapy with LHRH analogues for medical castration in patients with breast or prostate cancer, which are permitted
• Potent inhibitors or inducers or substrates of CYP3A4 or substrates of CYP2D6 within 2 weeks before the first dose of study treatment (3 weeks for St John"s Wort).
• Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment
• Radiotherapy with a wide field of radiation within 4 weeks of the first dose of study treatment
• Prior ATP-competitive AKT inhibitors

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (3)

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Shrestha Bhattarai T, Shamu T, Gorelick AN, Chang MT, Chakravarty D, Gavrila EI, Donoghue MTA, Gao J, Patel S, Gao SP, Reynolds MH, Phillips SM, Soumerai T, Abida W, Hyman DM, Schram AM, Solit DB, Smyth LM, Taylor BS. AKT mutant allele-specific activation dictates pharmacologic sensitivities. Nat Commun. 2022 Apr 19;13(1):2111. doi: 10.1038/s41467-022-29638-1.

  PMID: 35440569 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Breast Neoplasms; Prostatic Neoplasms

Interventions

capivasertib; enzalutamide; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Alison Schram, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be an open label, single institution, non-randomized, pilot study.

Study Record Dates

• First Submitted: October 11, 2017
• First Posted: October 16, 2017
• Study Start: October 11, 2017
• Primary Completion: May 3, 2023
• Study Completion: May 3, 2023
• Last Updated: May 6, 2023

Record last verified: 2023-05

Locations

US (3)