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Advanced Solid TumoursPhase 1NCT02579226

A Phase I Study of Safety, Tolerability, and PK of AZD2811 in Patients With Advanced Solid Tumors.

A Phase 1 study testing AZD2811 in people with Advanced Solid Tumours, run by AstraZeneca at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This Phase I study is primarily designed to evaluate the safety and tolerability of AZD2811 at increasing doses in patients with advanced solid tumours and for whom no standard of care exists. The study will be conducted in two parts, a dose-escalation phase (Part A) and a dose expansion phase (Part B). Read more about this study

Who is it for?
Ages 18 to 130 years
Conditions the study is for
Advanced Solid Tumours
What is being tested?
AZD2811
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
6 sitesUnited States
Study dates
28 Oct 2015to 3 Apr 2020
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 to 130 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Part A Dose Escalation:
  • Histological or cytological confirmation of a solid tumour and disease progression despite standard therapy(ies), or they must be intolerant to standard therapy(ies), or no standard therapy exists.
  • Patients must have received ≤3 prior chemotherapy regimens in the metastatic setting which may have included irinotecan.
  • Part B Dose Expansion:
  • 1. Patients must have received at least 1 prior platinum-based systemic therapy but no more than 3 prior systemic regimens for relapsed and/or refractory SCLC.
  • Measurable or non-measurable (but evaluable disease) according to RECIST v1.1.
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  • Age ≥18
  • Adequate organ system functions, as outlined by a) absolute neutrophil count (ANC) ≥1.5 X 10^9/L, b) platelets ≥100 X 10^9/L, c) hemoglobin ≥9 g/dL, d) PT/PTT/INR ≤1.5 x upper limit of normal (ULN), e) total bilirubin ≤1.5 mg/dL, f) ALT and AST ≤3.0 times the ULN if no liver involvement or ≤5 times the ULN with liver involvement, g) creatinine ≤1.5 x ULN, OR calculated or measured creatinine clearance ≥50 mL/min, OR 24-hour measured urine creatinine clearance ≥50 mL/min
  • ECOG performance status 0-1.
  • Must provide an archived tissue sample for correlative testing, if available. If archived tissue is not available, patient will still be eligible for enrolment into the study.
  • Predicted life expectancy ≥12 weeks.
  • Females of child-bearing potential should be using adequate contraceptive measures from the time of screening until 6 months after study discontinuation, should not be breast feeding and must have a negative pregnancy test prior to start of dosing. Females of non-child-bearing potential must have evidence by the following criteria at screening: a) post-menopausal defined as aged > 50 and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments, b) documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not tubal ligation, c) women < 50 would be considered postmenopausal if they have been amenorrhoeic for > 12 months following cessation of all exogenous hormonal treatments, and have serum follicle-stimulating hormone and luteinizing hormone levels in the postmenopausal range.
  • Sexually active males should be willing to use barrier contraception (i.e., condoms).

Who cannot join

  • Patients who have been treated with most recent radiotherapy, immunotherapy, chemotherapy or investigational drugs within ≤21 days or 5 half-lives (whichever is shorter) from enrolment (screening), and/or who have any unresolved NCI Common Terminology Criteria of Adverse Events (CTCAE) v4.03 > Grade 1 treatment-related side effect, with the exceptions of alopecia, should not be enrolled.
  • Major surgery (excluding placement of vascular access) ≤21 days from beginning of the study drug or minor surgical procedures ≤7 days. No waiting is required following implantable port and catheter placement.
  • Previous treatment with alisertib.
  • Any of the following cardiac criteria: a) Congestive heart failure (CHF) per New York Heart Association (NYHA) classification > Class II, b) Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy, c) Unstable angina or new-onset angina, d) QTcF interval >470 ms on screening ECG.
  • Active non-infectious skin disease (including any grade rash, urticarial, dermatitis, ulceration, or psoriasis, but excluding stable plaque psoriasis from the definition of active disease).
  • Patients with diarrhoea NCI CTCAE v4.03 Grade ≥2.
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  • Patient has had prescription or non-prescription drugs or other products known to be strong inhibitors/inducers of CYP3A4 which cannot be discontinued prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug.
  • Any evidence of active infection, severe or uncontrolled systemic diseases including uncontrolled hypertension, active bleeding diatheses, hepatitis B, hepatitis C and human immunodeficiency virus.
  • Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 3 weeks previously and there is no evidence of central nervous system disease progression, mild neurologic symptoms, and no requirement for chronic corticosteroid therapy.
  • Treatment with haematopoietic colony-stimulating factors (e.g., G-CSF) ≤2 weeks prior to screening visit.
  • History of hypersensitivity to active or inactive excipients (e.g., PEG) of any drug in the study or drugs with similar chemical structure or class to those being investigated in the study.
  • Lactating, breastfeeding, or positive pregnancy test for female patients of child-bearing potential.
  • Concurrent conditions that in the Investigator's opinion would jeopardize compliance with the protocol.
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Research Site

    Boston, Massachusetts, 02215

  • Research Site

    Denver, Colorado, 80218

  • Research Site

    Houston, Texas, 77030

  • Research Site

    Milwaukee, Wisconsin, 53226

  • Research Site

    Nashville, Tennessee, 37203

  • Research Site

    Sarasota, Florida, 34232

Other trials in United States

About this study

Official title: A Phase I, Open-Label, Multicentre Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD2811 in Patients With Advanced Solid Tumours.

This Phase I study is primarily designed to evaluate the safety and tolerability of AZD2811 at increasing doses in patients with advanced solid tumours and for whom no standard of care exists. The study will be conducted in two parts, a dose-escalation phase (Part A) and a dose expansion phase (Part B). During Part A, the dose-escalation phase, patient enrolment will proceed according to a 3+3 design where the maximum tolerated dose (MTD) or the recommended Phase II dose (RP2D) could be identified. The study will also characterize the pharmacokinetic (PK) profile of AZD2811 and will explore the potential biological activity by assessing anti-tumour activity in patients. Part B will further explore PK parameters, safety, tolerability, and preliminary anti-tumour activity of the AZD2811 RP2D as monotherapy (Group 1) in patients with relapsed/refractory SCLC.

Read the detailed description

This is a first-time-in-patient (FTIP) study with the nanoparticle formulation of AZD2811 primarily designed to evaluate the safety and tolerability of AZD2811 at increasing doses in patients with advanced solid tumours and for whom no standard of care exists.

The study will be conducted in two parts: Part A dose-escalation and Part B dose-expansion. In Part A, the dose-escalation phase, patient enrolment has proceeded according to a 3+3 design in order to identify the maximum-tolerated dose (MTD) or recommended Phase 2 dose (RP2D). AZD2811 monotherapy has been administered IV to patients with advanced solid tumours on Days 1 and 4 of a 28-day cycle in 6 dose levels without any relevant toxicities in the first 5 patient cohorts. In Cohort 6 (200 mg), grade 4 asymptomatic neutropenia was observed, and a dose-limiting toxicity was observed in 1 patient of the 5 evaluable patients. In Cohort 7 AZD2811 (200 mg) was given on Day 1 only of a 28-day cycle; in Cohort 8 AZD2811 (200 mg) was given on Day 1 only of a 21-day cycle. In Cohort 9, the AZD2811 dose was escalated to 400 mg on Day 1 every 21 days.

The Safety Review Committee (SRC) will review the safety and tolerability of AZD2811 for each cohort and schedule to determine the next cohorts. The study will also characterize the pharmacokinetic (PK) profile of AZD2811 and will explore potential biological activity by assessing anti-tumour activity in patients.

Once the MTD is established, Part B the dose expansion phase will continue to explore PK parameters, safety, tolerability, and preliminary anti-tumour activity of the AZD2811 RP2D as monotherapy in 21 patients with relapsed/refractory SCLC.

Being tested
AZD2811
Keywords
AZD2811, Advanced solid tumours, Small-cell lung cancer
Medical subject headings
Small Cell Lung Carcinoma

What participants receive

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

  • AZD2811Drug

    The study will be conducted in 2 parts, dose-escalation (A) and dose-expansion (B). All patients in both parts of the study with receive AZD2811.

Study groups in NCT02579226
Study groupRoleWhat they receive
Part AExperimentalPart A dose-escalation will evaluate the safety and tolerability of AZD2811 monotherapy at increasing doses in patients with advanced solid tumours. Patients will receive AZD2811 on Days 1 and 4 of a 28-day cycle or Day 1 only in cycles of either 21 or 28 days.
Receives: Drug: AZD2811
Part BExperimentalPart B will include patients with relapsed or refractory small-cell lung cancer (SCLC). Patients will receive AZD2811 monotherapy at the recommended Phase 2 dose (RP2D).
Receives: Drug: AZD2811

What is being measured

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

  1. The incidence of dose-limiting toxicites (DLTs)

    Maximum Tolerated Dose (MTD) will be determined in Part A of the study by assessing the incidence of Dose Limiting Toxicities (DLTs), adverse events, and abnormal laboratory results.

    DLT is defined as:

    1. Grade 4 neutropenia for > 7 days, or febrile neutropenia.
    2. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding.
    3. Concurrent Grade ≥3 total bilirubin, ALT or AST or alkaline phosphatase lasting > 48 hours, or any change in liver function test results consistent with Hy's Law.
    4. Grade ≥3 non-hematologic AE except: a) Grade 3 diarrhoea controlled within 4 days with standard supportive care, b) Grade 3 elevations in ALT/AST that return to meet initial eligibility criteria within 7 days of study drug interruption.
    5. Inability to receive all doses in Cycle 1 due to treatment-related toxicity.
    6. Non-haematologic toxicity of ≥ Grade 2 (at any time during treatment) that, in the judgment of the Investigator and the Medical Monitor, is dose limiting.

    Measured: Patients will be followed for either 21 or 28 days in Cycle 1 to determine the incidence of Dose Limiting Toxicities (DLTs).

  2. The incidence of adverse events

    Maximum Tolerated Dose (MTD) will be determined in Part A of the study by assessing the incidence of Dose Limiting Toxicities (DLTs), adverse events, and abnormal laboratory results.

    At least 3 evaluable patients will be enrolled at each dose level (3+3 design) and will be evaluated for 21 or 28 days before escalation to the next dose level can occur. If one patient experiences a DLT, an additional 3 patients will be treated with the same dose. Therefore, a maximum of up to 6 patients may be enrolled per dose level.

    Measured: Patients will be followed for either 21 or 28 days in Cycle 1 to determine the incidence of adverse events

  3. The incidence of abnormal laboratory results

    Maximum Tolerated Dose (MTD) will be determined in Part A of the study by assessing the incidence of Dose Limiting Toxicities (DLTs), adverse events, and abnormal laboratory results.

    At least 3 evaluable patients will be enrolled at each dose level (3+3 design) and will be evaluated for 21 or 28 days before escalation to the next dose level can occur. If one patient experiences a DLT, an additional 3 patients will be treated with the same dose. Therefore, a maximum of up to 6 patients may be enrolled per dose level.

    Measured: Patients will be followed for either 21 or 28 days in Cycle 1 to determine the incidence of abnormal laboratory results.

Secondary outcomes (11)

  1. Maximum plasma concentration (Cmax) of encapsulated AZD2811, released AZD2811, and AZD2811 metabolites

    PK parameters will be derived by non-compartment analysis.

    Measured: Blood will be taken from subjects in Part A Cycle 1/Day 1: pre-dose, 1, 2, 4, 6, 8, 24, and 48 hr post dose; and Day 4: pre-dose, 1, 2, 4, 6, 8, 24, 48, 96, 336, 360, and 504 hr post dose, and Cycle 2/Day 1 pre-dose and 2 hr post dose.

  2. Time to maximum plasma concentration (tmax) for encapsulated AZD2811, released AZD2811, and AZD2811 metabolites.

    PK parameters will be derived by non-compartment analysis.

    Measured: Blood will be taken from subjects in Part A Cycle 1/Day 1: pre-dose, 1, 2, 4, 6, 8, 24, and 48 hr post dose; and Day 4: pre-dose, 1, 2, 4, 6, 8, 24, 48, 96, 336, 360, and 504 hr post dose, and Cycle 2/Day 1 pre-dose and 2 hr post dose.

  3. Area under the plasma concentration-time curve from zero to the last measurable concentration [AUC(0-t)] for encapsulated AZD2811, released AZD2811, and AZD2811 metabolites.

    PK parameters will be derived by non-compartment analysis.

    Measured: Blood will be taken from subjects in Part A Cycle 1/Day 1: pre-dose, 1, 2, 4, 6, 8, 24, and 48 hr post dose; and Day 4: pre-dose, 1, 2, 4, 6, 8, 24, 48, 96, 336, 360, and 504 hr post dose.

  4. Area under the plasma concentration-time curve from zero extrapolated to infinity [AUC(0-inf)] for encapsulated AZD2811, released AZD2811, and AZD2811 metabolites.

    PK parameters will be derived by non-compartment analysis.

    Measured: Blood will be taken from subjects in Part A Cycle 1/Day 1: pre-dose, 1, 2, 4, 6, 8, 24, and 48 hr post dose; and Day 4: pre-dose, 1, 2, 4, 6, 8, 24, 48, 96, 336, 360, and 504 hr post dose.

  5. Terminal rate constant (λz) for encapsulated AZD2811, released AZD2811, and AZD2811 metabolites.

    PK parameters will be derived by non-compartment analysis.

    Measured: Blood will be taken from subjects in Part A Cycle 1/Day 1: pre-dose, 1, 2, 4, 6, 8, 24, and 48 hr post dose; and Day 4: pre-dose, 1, 2, 4, 6, 8, 24, 48, 96, 336, 360, and 504 hr post dose.

  6. Terminal elimination half-life for encapsulated AZD2811, released AZD2811, and AZD2811 metabolites.

    PK parameters will be derived by non-compartment analysis.

    Measured: Blood will be taken from subjects in Part A Cycle 1/Day 1: pre-dose, 1, 2, 4, 6, 8, 24, and 48 hr post dose; and Day 4: pre-dose, 1, 2, 4, 6, 8, 24, 48, 96, 336, 360, and 504 hr post dose.

  7. Volume of distribution (Vz) for encapsulated AZD2811, released AZD2811, and AZD2811 metabolites.

    PK parameters will be derived by non-compartment analysis.

    Measured: Blood will be taken from subjects in Part A Cycle 1/Day 1: pre-dose, 1, 2, 4, 6, 8, 24, and 48 hr post dose; and Day 4: pre-dose, 1, 2, 4, 6, 8, 24, 48, 96, 336, 360, and 504 hr post dose.

  8. Objective Response Rate (ORR), including the number of complete and partial responses

    Baseline tumour imaging studies [computerized tomography (CT)] scan of the chest and abdomen/pelvis) will be performed within 28 days prior to the first dose of study drug (AZD2811) and will be repeated at the completion of Cycle 2 (Week 6 or Week 8) according the RECIST v1.1.

    Measured: Patients will be assessed after every two treatment cycles (6 or 8 weeks) for up to 1 year and every 12 weeks thereafter

  9. The incidence of Stable Disease (SD)

    Baseline tumour imaging studies [computerized tomography (CT)] scan of the chest and abdomen/pelvis) will be performed within 28 days prior to the first dose of study drug (AZD2811) and will be repeated at the completion of Cycle 2 (Week 6 or Week 8) according the RECIST v1.1.

    Measured: Patients will be assessed after every two treatment cycles (6 or 8 weeks) for up to 1 year and every 12 weeks thereafter

  10. The incidence of Progressive Disease (PD)

    Baseline tumour imaging studies [computerized tomography (CT)] scan of the chest and abdomen/pelvis) will be performed within 28 days prior to the first dose of study drug (AZD2811) and will be repeated at the completion of Cycle 2 (Week 6 or Week 8) according the RECIST v1.1.

    Measured: Patients will be assessed after every two treatment cycles (6 or 8 weeks) for up to 1 year and every 12 weeks thereafter

  11. The proportion of patients surviving at 6 months will assessed in Part B.

    Measured: Survival will be determined at 6 months

Timeline

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

  1. First posted19 Oct 2015 (estimated)
  2. Study start28 Oct 2015
  3. Primary completion7 Feb 2020
  4. Study completion3 Apr 2020

Resources

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
Masking
None (open label)
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02579226
Sponsor's protocol ID
D6130C00001
Other IDs
REFMAL 390
Status last verified
Apr 2020
First submitted
8 Sep 2015
Last updated
1 May 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Publications

  • Johnson ML, Fabbri G, Ciardullo C, Wang JS, Falchook GS, Jones S, Strickland D, Sands J, Gay CM, Cardnell RJ, Tobalina L, Willis SE, Rodriguez-Canales J, Nikolaou M, Jones EV, Schalkwijk S, Sainsbury L, MacDonald A, Overend P, Kennedy C, Pease JE, Szekeres P, Cosaert J, Burris H 3rd, Byers LA. Treatment monitoring by biomarker analysis in a Phase I dose-expansion study of AZD2811 for relapsed/refractory small-cell lung cancer. Br J Cancer. 2026 Jun;134(11):1592-1604. doi: 10.1038/s41416-026-03414-0. Epub 2026 Apr 3.

    PubMed 41933194

  • Johnson ML, Wang JS, Falchook G, Greenlees C, Jones S, Strickland D, Fabbri G, Kennedy C, Elizabeth Pease J, Sainsbury L, MacDonald A, Schalkwijk S, Szekeres P, Cosaert J, Burris H 3rd. Safety, tolerability, and pharmacokinetics of Aurora kinase B inhibitor AZD2811: a phase 1 dose-finding study in patients with advanced solid tumours. Br J Cancer. 2023 May;128(10):1906-1915. doi: 10.1038/s41416-023-02185-2. Epub 2023 Mar 4.

    PubMed 36871042

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD2811 in people with Advanced Solid Tumours, run by AstraZeneca at 6 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 13 inclusion and 14 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 1 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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?

The incidence of dose-limiting toxicites (DLTs) (time frame: Patients will be followed for either 21 or 28 days in Cycle 1 to determine the incidence of Dose Limiting Toxicities (DLTs).). The study lists 3 primary outcomes in all. 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 NCT02579226, which also lists 2 linked publications.

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 1 May 2020.

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