Breast CancerPhase 1NCT03310541
AZD5363 in Patients With Advanced Solid Tumors Harboring AKT Mutations
A Phase 1 study testing AZD5363, Enzalutamide and Fulvestrant in people with Breast Cancer and Prostate Cancer, run by Memorial Sloan Kettering Cancer Center at 3 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Prostate Cancer, Advanced Solid Tumors
- What is being tested?
- AZD5363, Enzalutamide and Fulvestrant
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 3 sitesUnited States
- Study dates
- 11 Oct 2017to 3 May 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
- Male patients should be willing to use barrier contraception (i.e. condoms)
Who cannot join
- 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%
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- 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
- With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment
- Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment
- As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus. Screening for chronic conditions is not required.
- Any of the following cardiac criteria:
- Resting corrected QT interval (QTc) > 480 msec obtained from electrocardiogram (ECG)
- Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) eg, complete left bundle branch block, third degree heart block
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
- Experience of any of the following procedures or conditions in the preceding 6 months and judged to be clinically significant by Principle Investigator: : coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) Grade ≥2
- Uncontrolled hypotension - Systolic blood pressure (BP) <90mmHg and/or diastolic BP <50mmHg
- Left ventricular ejection fraction (LVEF) below lower limit of normal for site.
- Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
- Absolute neutrophil count < 1 x 10^9/L
- Platelet count < 100 x 10^9/L
- Haemoglobin < 9.0 g/dL
- ALT > 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases, or >5 times ULN in presence of liver metastases
- AST > 2.5 times ULN if no demonstrable liver metastases, or >5 times ULN in presence of liver metastases.
- Total bilirubin > 1.5 times ULN (patients with confirmed Gilbert"s syndrome may be included in the study)
- Creatinine >1.5 times ULN concurrent with creatinine clearance < 50 ml/min; confirmation of creatinine clearance is only required when creatinine is > 1.5 times ULN
- Proteinuria 3+ on dipstick analysis or >500 mg/24 hours
- Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5363
- History of hypersensitivity to active or inactive excipients of AZD5363, fulvestrant and enzalutamide or drugs with a similar chemical structure or class to these agents.
- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Pilot Study of AZD5363 for Patients With Advanced Solid Tumors Harboring Mutations in AKT1, AKT2, or AKT3
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
- Being tested
- AZD5363, Enzalutamide, Fulvestrant
- Keywords
- AZD5363, AKT Mutations, 17-322
- Medical subject headings
- Breast Neoplasms, Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD5363Drug
AZD5363 400mg PO twice daily for 4 days on, 3 days off, every week
EnzalutamideDrug
Enzalutamide 160 mg PO once daily
FulvestrantDrug
500mg IM days 1, 15, 29 (cycle 2 day 1) and then every 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: AZD5363 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2017
- Study start11 Oct 2017
- Primary completion3 May 2023
- Study completion3 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This will be an open label, single institution, non-randomized, pilot study.
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alison Schram, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03310541
- Sponsor's protocol ID
- 17-322
- Status last verified
- May 2023
- First submitted
- 11 Oct 2017
- Last updated
- 6 May 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 35440569
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of AZD5363 for Patients With Advanced Solid Tumors Harboring Mutations in AKT1, AKT2, or AKT3
- ClinicalTrials.gov ID
- NCT03310541
- Acronym / sponsor ID
- 17-322
- Conditions
- Breast Cancer, Prostate Cancer, Advanced Solid Tumors
- Keywords
- AZD5363, AKT Mutations, 17-322
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- 11 Oct 2017 (actual)
- Primary completion
- 3 May 2023 (actual)
- Study completion
- 3 May 2023 (actual)
- First posted
- 16 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This will be an open label, single institution, non-randomized, pilot study.
| Arm | Type | Receives |
|---|---|---|
| Prostate, Previously treated with Enzalutamide | Experimental | Drug: AZD5363, Drug: Enzalutamide28-DAY CYCLE AZD5363 400mg PO twice daily for 4 days on, 3 days off, every week + Enzalutamide 160 mg PO once daily |
| ER+ Breast, Previously treated with Fulvestrant | Experimental | Drug: AZD5363, Drug: Fulvestrant28-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 |
| Advanced Solid Tumors | Experimental | Drug: AZD536328-DAY CYCLE AZD5363 480mg PO twice daily for 4 days on, 3 days off, every week |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (37 listed)
- 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]:
- Glycosylated haemoglobin (HbA1C) ≥8.0%
- Requirement for insulin for routine diabetic management and control
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD5363AZD5363 400mg PO twice daily for 4 days on, 3 days off, every week | Drug | Advanced Solid Tumors, ER+ Breast, Previously treated with Fulvestrant, Prostate, Previously treated with Enzalutamide |
| EnzalutamideEnzalutamide 160 mg PO once daily | Drug | Prostate, Previously treated with Enzalutamide |
| Fulvestrant500mg IM days 1, 15, 29 (cycle 2 day 1) and then every 4 weeks | Drug | ER+ Breast, Previously treated with Fulvestrant |
Primary outcome
number of patients with an objective response rate (ORR) of AZD5363
Time frame: 1 year
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2023.
- Derived from this study: PubMed 35440569Shrestha 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.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alison Schram, MD principal investigator
Memorial Sloan Kettering Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD5363, Enzalutamide and Fulvestrant in people with Breast Cancer and Prostate Cancer, run by Memorial Sloan Kettering Cancer Center at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of patients with an objective response rate (ORR) of AZD5363 (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03310541, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2023.