Neoplasms, HaematologicPhase 1NCT02177682

Study of Afuresertib Monotherapy in Japanese Relapsed Multiple Myeloma Patients

A Phase 1 study testing Afuresertib in people with Neoplasms, Haematologic, run by Novartis Pharmaceuticals at 5 sites in Japan.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 20 years and older
Conditions the study is for: Neoplasms, Haematologic
What is being tested?: Afuresertib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 9 participants
Where: 5 sitesJapan
Study dates: 13 Aug 2014to 14 Aug 2019
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 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Written informed consent is provided.
Japanese females or males aged 20 years or older (at the time consent is obtained).
Histologically confirmed diagnosis of relapsed multiple myeloma.
Performance score of 0 and 1 according to the ECOG scale.
Relapsed after at least 1 line of systemic therapy. The preparative regimen (with or without total body irradiation) and subsequent autologous stem cell rescue used for an autologous stem cell transplant are considered as one line of therapy.
Able to swallow and retain oral medication.

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Male subjects with a female partner of childbearing potential must have had a prior vasectomy or agree to use adequate contraception from the time of the first dose of study drug until three months after the last dose of study drug.
A female subject is eligible to participate if she is of: (A) Non-childbearing potential (i.e. physiologically incapable of becoming pregnant): Pre-menopausal females with a documented tubal ligation or hysterectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea [if unclear, simultaneous follicle stimulating hormone >40 milli-international units (MIU)/milliliter (mL) and oestradiol <40 picograms (pg)/mL (<140 picomoles [pmol]/L) is required as confirmation]. (B) Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt must discontinue HRT to confirm post-menopausal status prior to study enrolment. Following confirmation, they can resume HRT during the study without use of a contraceptive method. (C) Child-bearing potential, has a negative serum pregnancy test within 7 days prior to enrolment, and agrees to use adequate contraception from screening until four weeks after the last dose of study drug. Note: The recommended contraceptive methods are abstinence of sexual intercourse, use of intrauterine device/system, vasectomy, and use of condom with spermicidal agent. An oral contraceptive drug does not offer a reliable contraceptive method as a drug-drug interaction may occur.
Adequate organ system functions as defined in the protocol
Subjects with a history of autologous stem cell transplant are eligible provided the following criteria are met: transplant completed >180 days prior to enrolment; no active infection (e.g. cytomegalovirus, varicella-zoster virus); meets the remainder of the eligibility criteria outlined in this protocol.

Who cannot join

Chemotherapy, radiotherapy, immunotherapy or other anti-myeloma therapy within 28 days prior to enrolment. In addition, any toxicity (except alopecia) should be recovered to <=Grade 1 by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.0.
Use of an investigational drug within 30 days or five half-lives, whichever is longer.
History of an allogenic stem cell transplant. For patients with history of autologous stem cell transplant, inclusion criteria 10 must be met.
History of PI3K/AKT inhibitors.
Current use of prohibited medication or subject who requires any of these medications during treatment of afuresertib, as well as subject who cannot meet the protocol specified meals and dietary restrictions
Current use of oral corticosteroids, except inhaled or topical use.

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Uncontrolled diabetes mellitus by diet, exercise or medicinal therapies including insulin, and with fasting serum glucose >=130 mg/dL (>=7.28 millimoles [mmol]/L).
Use of anticoagulants other than low dose (prophylactic) anticoagulants for subject whose Prothrombin time (PT)/international normalization ratio (INR) and activated partial thromboplastin time (APTT) is <=1.5 x upper limit of normal (ULN).
Presence of active Gastro-intestinal (GI) disease or other condition that could affect GI absorption (e.g. malabsorption syndrome) or predispose subject to GI ulceration.
Any major surgery that required hospitalization within last four weeks.
Any serious or unstable pre-existing medical, psychiatric, or other conditions (including lab abnormalities) that could interfere with subject safety or obtaining informed consent.
Active infection requiring parenteral or oral anti-infective treatment.
Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, or cardiac disease).
Central nervous system malignancies, primary or metastatic.
Diagnosis of or treatment history for another malignancy within 2 years, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
History of known infection with human immunodeficiency virus (HIV).
Positive hepatitis B surface (HBs) antigen or hepatitis B virus (HBV) Deoxyribonucleic acid (DNA). If negative for HBs antigen and positive for both or either of hepatitis B core (HBc) and HBs antibodies, HBV DNA needs to be negative.
Positive hepatitis C virus (HCV) antibody
Corrected QT interval (QTc) >450 milliseconds (msec) or QTc > 480 msec for patients with bundle branch block. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF). Note: The QTc should be based on single or averaged QTc values of triplicate ECGs obtained over a brief recording period.
Other clinically significant ECG abnormalities, including 2nd or 3rd degree atrioventricular block.
History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty or stenting or bypass grafting within the past six months.
Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
Pregnant or lactating female.
Known hypersensitivity to any components of the study treatment.
Others who are considered as inappropriate to participate in this study by investigators.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

Japan5 sites

Novartis Investigative Site
Aichi, 467-8602
Novartis Investigative Site
Fukuoka, 811-1395
Novartis Investigative Site
Miyagi, 980-8574
Novartis Investigative Site
Niigata, 951-8566
Novartis Investigative Site
Tokyo, 104-0045

Other trials in Japan

About this study

Official title: An Open-label, Dose Escalation, Phase I Study to Evaluate the Tolerability, Safety and Pharmacokinetics of Afuresertib Monotherapy in Japanese Relapsed Multiple Myeloma Patients.

Afuresertib, an AKT inhibitor, has shown in vitro and in vivo activity in multiple myeloma models. AKT inhibitor has also demonstrated encouraging clinical activity in multiple myeloma. This study is designed to determine the tolerability, safety, pharmacokinetics and efficacy of afuresertib as monotherapy in Japanese relapsed multiple myeloma patients. This is an open label, dose-escalating, phase I study. Afuresertib will be given daily until the subjects meet any study treatment withdrawal criteria including disease progression. A total of up to 24 subjects will be enrolled in the study.

Conditions: Neoplasms, Haematologic
Being tested: Afuresertib
Keywords: AKT inhibitor, Afuresertib, multiple myeloma
Medical subject headings: Neoplasms, Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AfuresertibDrug
Size 4 and Size 1 opaque white capsules containing 25 mg and 100 mg of afuresertib, respectively, to be administered orally.

Study groups in NCT02177682
Study group	Role	What they receive
Afuresertib	Experimental	Three subjects will be enrolled and given afuresertib 125 mg orally and monitored for toxicity. After completion of PK sampling in 3 days (Cycle 0), daily repeated dose of 125 mg will be given for 21 days (Cycle 1). If no DLT event is found after 21 days of repeated dosing, up to 6 subjects will be enrolled and given afuresertib 150 mg. If afuresertib 150 mg is assessed to be tolerable, up to 6 subjects can be enrolled and given afuresertib 200 mg. If afuresertib 200 mg is assessed to be intolerable, up to 6 subjects will be enrolled and given afuresertib 150mg or 175 mg. In any Dose levels, if DLT occurs in more than 2 subjects, that Dose level will be considered as intolerable." Receives: Drug: Afuresertib

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of subjects with Dose-limiting toxicities (DLTs) when afuresertib is given as monotherapy
DLT is defined as an adverse event which is applicable to any of the criteria specified in the protocol and judged to have a reasonable causal relationship with afuresertib. The DLT evaluation period will be from the day of the first dosing in Cycle 1 to Day 21 of Cycle 1 or the day of DLT occurrence if any DLT occurred before Day 21 of Cycle 1.
Measured: Day 1 to 21 of Cycle 1

Secondary outcomes (8)

Eastern Cooperative Oncology Group (ECOG) performance status (PS)
The performance status will be assessed using the ECOG scale
Measured: From Day -3 until 30 days after the last dose of afuresertib
Vital signs assessment
Vital sign measurements will include systolic and diastolic blood pressure and pulse rate
Measured: From Day -3 until 30 days after the last dose of afuresertib
Number of participants with adverse events (AEs)
An AE is defined as any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
Measured: From Day -3 until 30 days after the last dose of afuresertib
Laboratory assessments
laboratory assessments will include haematologic tests, blood chemistry tests, coagulation tests, urine tests and lipid panel
Measured: From Day -3 until 30 days after the last dose of afuresertib
12-lead electrocardiogram (ECG) assessment
Triple 12-lead ECGs will be obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures pulse rate (PR), QRS, QT, and QTc intervals.
Measured: From Day -3 until 30 days after the last dose of afuresertib
Left ventricular ejection fraction (LVEF) assessment
Echocardiogram and/or Multi-gated Acquisition (MUGA) scans will be performed for evaluation for LVEF
Measured: From Day -3 until 30 days after the last dose of afuresertib
Composite of pharmacokinetic (PK) parameters of afuresertib monotherapy administered as single and repeated dose
PK parameters will include area under the concentration-time curve from time zero extrapolated to infinite time [AUC (0-infinity)], area under the concentration-time curve over the dosing interval [AUC (0-tau)], maximum observed plasma concentration (Cmax), last observed quantifiable concentration (Clast), apparent clearance following oral dosing (CL/F), pre-dose (trough) concentration at the end of the dosing interval (Ctau), time of occurrence of Cmax (tmax), terminal phase half-life (t1/2), steady state ratio (Rs) and observed accumulation ratio (Ro)
Measured: Cycle 0 (Pre-dose, 0.5 hour [hr],1 hr, 2 hr, 3 hr, 4hr, 6 hr, 8 hr, 24 hr, 48 hr, 72 hr) and Cycle 1 Day 8 (Pre-dose, 0.5 hr,1 hr, 2 hr, 3 hr, 4hr, 6 hr, 8 hr, 24 hr)
Response rate and clinical benefit rate (rate of minor response or better)
Response evaluations will be determined according to the Response Criteria for multiple myeloma as stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), and minor response (MR). Response rate will be defined as the percentage of subjects with sCR, CR, VGPR or PR. Subjects with unknown or missing response will be treated as non-responder.
Measured: Within 4 weeks of Day 1 Cycle 1, at start of each cycle (except Cycle 1), and then every 6 to 9 weeks until 30 days after the last dose of afuresertib

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Aug 201414 Aug 2019

First posted30 Jun 2014 (estimated)
Study start13 Aug 2014
Primary completion9 Feb 2017
Study completion14 Aug 2019

Why it stopped: Company decision

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Neoplasms, HaematologicStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 9 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02177682
Sponsor's protocol ID: 115960
Status last verified: Aug 2021
First submitted: 29 May 2014
Last updated: 11 Aug 2021
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Neoplasms, Haematologic trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Dose Escalation, Phase I Study to Evaluate the Tolerability, Safety and Pharmacokinetics of Afuresertib Monotherapy in Japanese Relapsed Multiple Myeloma Patients.
ClinicalTrials.gov ID: NCT02177682
Acronym / sponsor ID: 115960
Conditions: Neoplasms, Haematologic
Keywords: AKT inhibitor, Afuresertib, multiple myeloma
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Company decision
Enrolment: 9 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 13 Aug 2014 (actual)
Primary completion: 9 Feb 2017 (actual)
Study completion: 14 Aug 2019 (actual)
First posted: 30 Jun 2014 (estimated)
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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Afuresertib	Experimental	Drug: AfuresertibThree subjects will be enrolled and given afuresertib 125 mg orally and monitored for toxicity. After completion of PK sampling in 3 days (Cycle 0), daily repeated dose of 125 mg will be given for 21 days (Cycle 1). If no DLT event is found after 21 days of repeated dosing, up to 6 subjects will be enrolled and given afuresertib 150 mg. If afuresertib 150 mg is assessed to be tolerable, up to 6 subjects can be enrolled and given afuresertib 200 mg. If afuresertib 200 mg is assessed to be intolerable, up to 6 subjects will be enrolled and given afuresertib 150mg or 175 mg. In any Dose levels, if DLT occurs in more than 2 subjects, that Dose level will be considered as intolerable."

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Written informed consent is provided.
Japanese females or males aged 20 years or older (at the time consent is obtained).
Histologically confirmed diagnosis of relapsed multiple myeloma.
Performance score of 0 and 1 according to the ECOG scale.
Relapsed after at least 1 line of systemic therapy. The preparative regimen (with or without total body irradiation) and subsequent autologous stem cell rescue used for an autologous stem cell transplant are considered as one line of therapy.

Key exclusion criteria (25 listed)

Chemotherapy, radiotherapy, immunotherapy or other anti-myeloma therapy within 28 days prior to enrolment. In addition, any toxicity (except alopecia) should be recovered to <=Grade 1 by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.0.
Use of an investigational drug within 30 days or five half-lives, whichever is longer.
History of an allogenic stem cell transplant. For patients with history of autologous stem cell transplant, inclusion criteria 10 must be met.
History of PI3K/AKT inhibitors.
Current use of prohibited medication or subject who requires any of these medications during treatment of afuresertib, as well as subject who cannot meet the protocol specified meals and dietary restrictions

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
AfuresertibSize 4 and Size 1 opaque white capsules containing 25 mg and 100 mg of afuresertib, respectively, to be administered orally.	Drug	Afuresertib

Primary outcome

Number of subjects with Dose-limiting toxicities (DLTs) when afuresertib is given as monotherapy
Time frame: Day 1 to 21 of Cycle 1
DLT is defined as an adverse event which is applicable to any of the criteria specified in the protocol and judged to have a reasonable causal relationship with afuresertib. The DLT evaluation period will be from the day of the first dosing in Cycle 1 to Day 21 of Cycle 1 or the day of DLT occurrence if any DLT occurred before Day 21 of Cycle 1.

8 secondary outcomes

Eastern Cooperative Oncology Group (ECOG) performance status (PS)
Time frame: From Day -3 until 30 days after the last dose of afuresertib
Vital signs assessment
Time frame: From Day -3 until 30 days after the last dose of afuresertib
Number of participants with adverse events (AEs)
Time frame: From Day -3 until 30 days after the last dose of afuresertib
Laboratory assessments
Time frame: From Day -3 until 30 days after the last dose of afuresertib
12-lead electrocardiogram (ECG) assessment
Time frame: From Day -3 until 30 days after the last dose of afuresertib
Left ventricular ejection fraction (LVEF) assessment
Time frame: From Day -3 until 30 days after the last dose of afuresertib
Composite of pharmacokinetic (PK) parameters of afuresertib monotherapy administered as single and repeated dose
Time frame: Cycle 0 (Pre-dose, 0.5 hour [hr],1 hr, 2 hr, 3 hr, 4hr, 6 hr, 8 hr, 24 hr, 48 hr, 72 hr) and Cycle 1 Day 8 (Pre-dose, 0.5 hr,1 hr, 2 hr, 3 hr, 4hr, 6 hr, 8 hr, 24 hr)
Response rate and clinical benefit rate (rate of minor response or better)
Time frame: Within 4 weeks of Day 1 Cycle 1, at start of each cycle (except Cycle 1), and then every 6 to 9 weeks until 30 days after the last dose of afuresertib

Results and safety

The study was stopped early (reason given: Company decision). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2021.
Novartis results databaseLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Neoplasms, Haematologic

RecruitingPhase 2
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Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
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RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
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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.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

5 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 Afuresertib in people with Neoplasms, Haematologic, run by Novartis Pharmaceuticals at 5 sites in Japan.

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 10 inclusion and 25 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: stopped early, as of the sponsor's last update on 11 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Japan. 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 was stopped early (reason given: Company decision). Results are not available in the source record.

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 subjects with Dose-limiting toxicities (DLTs) when afuresertib is given as monotherapy (time frame: Day 1 to 21 of Cycle 1). 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 NCT02177682.

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 11 Aug 2021.