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Ovarian Cancer, TNBC, SCLC, Other Solid TumoursPhase 1NCT02482311

Safety, Tolerance, PK, and Anti-tumour Activity of AZD1775 Monotherapy in Patients With Advanced Solid Tumours

A Phase 1 study testing AZD 1775 in people with Ovarian Cancer, TNBC, SCLC, Other Solid Tumours, run by AstraZeneca at 16 sites in 2 countries.

Completed

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

Official record
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Trial summary

This is an open-label, multi-centre, Phase Ib study of AZD1775 designed to assess the safety, tolerability, pharmacokinetics, and anti-tumour activity of AZD1775 monotherapy in patients with advanced solid tumours. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
AZD 1775
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
92 participants
Where
16 sitesin 2 countries
Study dates
1 Jul 2015to 22 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 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18
  • Previous chemotherapy for recurrent or metastatic disease.
  • Measurable disease is required for Part B expansion cohorts according to RECIST v1.1 criteria.
  • Radiation therapy completed at least 7 days prior to start of study treatment and patients must have recovered from any acute adverse effects.
  • ECOG Performance Status (PS) score of 0-1.
  • Baseline laboratory values as follows:
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  • ANC ≥1500/μL
  • Hgb ≥9 g/dL
  • Platelets ≥100,000/μL
  • ALT and AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases.
  • Serum bilirubin WNL or ≤1.5 x the ULN in patients with liver metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert's Syndrome.
  • Serum creatinine ≤1.5 x the ULN and a calculated creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method.
  • Negative serum or urine pregnancy test within 3 days prior to start of study treatment.
  • Fertile male patients willing to use at least one medically acceptable form of birth control for the duration of the study and for 2 weeks after treatment stops.
  • Predicted life expectancy ≥12 weeks.
  • Histologically or cytologically documented, locally advanced or metastatic solid tumour, excluding lymphoma, for which standard therapy does not exist or has proven ineffective or intolerable.
  • Has agreed to the collection of archival tumour tissue or recent tumour biopsy tissue, it taken for routine clinical purposes at baseline if archival tissue is not available, for molecular biomarker analyses.
  • Ovarian cancer defined as a histologically confirmed diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer refractory to standard therapies of for which no standard therapy exists. Confirmed BRCA1 or BRCA2 mutation from a prior test. Patient progressed while receiving and/or following treatment with a PARP-inhibitor for advanced disease (recurrent or metastatic.
  • Ovarian cancer confirmed BRCA wild-type from a prior test.
  • Triple-negative breast cancer (TNBC) defined as histologically confirmed diagnosis of breast cancer and must have received at least 1 chemotherapy-containing regimen for advanced disease (recurrent or metastatic). Tumour must be triple-negative, defined as minimal or no expression of estrogen and progesterone receptors [<10% of cells positive by immunohistochemistry (IHC)], and minimal or no expression of HER2 (IHC staining 0 or 1+ or FISH-).
  • Small-cell lung cancer (SCLC) defined as a histologically confirmed diagnosis of SCLC and must have received at least 1 chemotherapy-containing regimen for advanced disease (recurrent or metastatic).

Who cannot join

  • Any chemotherapy within 3 weeks of the first dose of AZD1775, except hormonal therapy in the refractory cohort.
  • Use of a study drug ≤21 days or 5 half-lives, whichever is shorter.
  • Major surgical procedures ≤28 days, or minor procedures ≤7 days.
  • Grade >1 toxicity from prior therapy (except alopecia or anorexia).
  • CNS disease other than neurologically stable, treated brain metastases.
  • Prescription or non-prescription drugs or other products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued two weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug.
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  • NYHA ≥ Class 2.
  • Mean resting corrected QT interval (QTc) ≥450 msec for males and ≥470 msec for females.
  • Pregnant or lactating.
  • Serious active infection, or serious underlying medical condition.
  • 12. Presence of other active invasive cancers. 13. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

Trial locations and contacts

16 sites in 2 countries.

16 sites in 2 countries

United States13 sites

  • Research Site

    Charlotte, North Carolina, 28204

  • Research Site

    Detroit, Michigan, 48201

  • Research Site

    Fayetteville, Arkansas, 72703

  • Research Site

    Fort Myers, Florida, 33905

  • Research Site

    Greenville, South Carolina, 29605

  • Research Site

    Houston, Texas, 77030

  • Research Site

    Indianapolis, Indiana, 46202

  • Research Site

    Milwaukee, Wisconsin, 53226

  • Research Site

    Nashville, Tennessee, 37203

  • Research Site

    Oklahoma City, Oklahoma, 73104

  • Research Site

    Philadelphia, Pennsylvania, 19104

  • Research Site

    San Francisco, California, 94143

  • Research Site

    West Hollywood, California, 90048

Other trials in United States

Canada3 sites

  • Research Site

    Edmonton, Alberta, T6G 1Z2

  • Research Site

    Toronto, Ontario, M5G 2M9

  • Research Site

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

About this study

Official title: A Phase Ib, Open-Label, Multi-Centre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-tumour Activity of AZD1775 Monotherapy in Patients With Advanced Solid Tumours

This is an open-label, multi-centre, Phase Ib study of AZD1775 designed to assess the safety, tolerability, pharmacokinetics, and anti-tumour activity of AZD1775 monotherapy in patients with advanced solid tumours.

Read the detailed description

This study is being conducted in two parts, designated Parts A and B. Part A is a safety lead-in consisting of a cohort of approximately 12 patients with advanced solid tumours.

Part B expansion cohorts will investigate AZD1775 monotherapy in advanced tumour types with molecular biomarkers of interest. The tumour types to be evaluated are: 1) ovarian cancer (BRCA1/2 mutation [PARP-failures]), 2) ovarian cancer (BRCA wild-type) with more than three prior lines of treatment, 3) triple negative breast cancer (TNBC), and 4) small-cell lung cancer (SCLC).

Being tested
AZD 1775
Keywords
AZD1775, Ovarian cancer (BRCA1/2 mutation), Ovarian cancer (PARP-failure), Triple negative breast cancer (TNBC), Small-cell lung cancer (SCLC), Solid tumours
Medical subject headings
Ovarian Neoplasms, Triple Negative Breast Neoplasms, Small Cell Lung Carcinoma

What participants receive

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

  • AZD 1775Drug

    AZD1775 will be taken orally approximately every 12 hours over 3 days at the start of week 1 and week 2 of each 21-day cycle (Days 1-3 and 8-10), for a total of 12 doses with each treatment cycle.

    AZD1775 should be taken approximately 2 hours before or 2 hours after food.

Study groups in NCT02482311
Study groupRoleWhat they receive
AZD1775ExperimentalSingle-arm study. AZD1775 will be administered for 3 consecutive days at the start of week 1 and week 2 of each 21-day cycle. This study will be conducted in two parts, designated Part A and Part B. Part A is a safety lead-in. Part B will commence after the safety lead-in and will investigate the safety and efficacy of AZD1775 monotherapy in expansion cohorts of specific tumour types.
Receives: Drug: AZD 1775

What is being measured

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

  1. Number of treatment emergent adverse events (TEAEs), serious adverse events (SAEs) and dose-limiting toxicities (DLTs) as a measure of safety and tolerability.

    The AZD1775 dose is considered safe and tolerable if ≤ 1 of 6 patients experiences a DLT.

    Measured: From first dose of study treatment up to last day of Cycle 1 (21 days)

Secondary outcomes (6)

  1. Objective Response Rate (ORR)

    The proportion of patients achieving a complete or partial tumour response (CR or PR) according to RECIST 1.1 criteria.

    Measured: Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, projected 12 months.

  2. Disease Control Rate (DCR)

    The proportion of patients achieving a complete response (CR) or partial response (PR), or stable disease (SD) according to RECIST v1.1 criteria

    Measured: Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, projected 12 months

  3. Duration of Response (DoR)

    The time from first documented tumor response until the date of documented progression or death from any cause.

    Measured: Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, projected 12 months

  4. Progression Free Survival (PFS)

    Defined as the time from date of first dose of AZD1775 until the date of objective disease progression or death by any cause as defined by RECIST 1.1.

    Measured: Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, project 12 months.

  5. PK profile: Plasma concentrations of AZD1775 and PK parameters (Cmax, C8hr, tmax, AUC, tlast, t½λz)

    Blood samples will be collected at various timepoints post-dosing

    Measured: Pre-dose and 1, 2, 4, 6, 8 and 12 hours post-dose of AZD1775 during Cycle 1-Day 1 and Cycle 1-Day3 or Day-10 of the safety lead-in part of study

  6. QTc prolongation

    ECGs will be obtained at various timepoints

    Measured: ECGs collected pre-dose and 1, 2, 4, 6, 8 and 12 hours post-dose in Cycle 1-Day 1 and on Cycle 1-Day 3 or Day 10.

Timeline

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

  1. First posted26 Jun 2015 (estimated)
  2. Study start1 Jul 2015
  3. Primary completion25 Jan 2018
  4. Study completion22 Aug 2019

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
Single group
Masking
None (open label)
Enrolment
92 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02482311
Sponsor's protocol ID
D6015C00001
Other IDs
REFMAL 383
Status last verified
Jun 2023
First submitted
11 Jun 2015
Last updated
3 Jul 2023
Results posted
No
Data monitoring committee
No

Publications

  • Bauer TM, Moore KN, Rader JS, Simpkins F, Mita AC, Beck JT, Hart L, Chu Q, Oza A, Tinker AV, Imedio ER, Kumar S, Mugundu G, Jenkins S, Chmielecki J, Jones S, Spigel D, Fu S. A Phase Ib Study Assessing the Safety, Tolerability, and Efficacy of the First-in-Class Wee1 Inhibitor Adavosertib (AZD1775) as Monotherapy in Patients with Advanced Solid Tumors. Target Oncol. 2023 Jul;18(4):517-530. doi: 10.1007/s11523-023-00965-7. Epub 2023 Jun 6.

    PubMed 37278879

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD 1775 in people with Ovarian Cancer, TNBC, SCLC, Other Solid Tumours, run by AstraZeneca at 16 sites in 2 countries.

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 21 inclusion and 11 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 3 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, Canada. 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 treatment emergent adverse events (TEAEs), serious adverse events (SAEs) and dose-limiting toxicities (DLTs) as a measure of safety and tolerability. (time frame: From first dose of study treatment up to last day of Cycle 1 (21 days)). 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 NCT02482311, 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 3 Jul 2023.

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