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

NCT ID: NCT02482311

Last Updated: 2023-07-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

92 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-07-01

Study Completion Date

2019-08-22

Brief Summary

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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.

Detailed Description

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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).

Conditions

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Ovarian Cancer, TNBC, SCLC, Other Solid Tumours

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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AZD1775

Single-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.

Group Type EXPERIMENTAL

AZD 1775

Intervention Type DRUG

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.

Interventions

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AZD 1775

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age ≥18
2. Previous chemotherapy for recurrent or metastatic disease.
3. Measurable disease is required for Part B expansion cohorts according to RECIST v1.1 criteria.
4. Radiation therapy completed at least 7 days prior to start of study treatment and patients must have recovered from any acute adverse effects.
5. ECOG Performance Status (PS) score of 0-1.
6. Baseline laboratory values as follows:

1. ANC ≥1500/μL
2. Hgb ≥9 g/dL
3. Platelets ≥100,000/μL
4. ALT and AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases.
5. 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.
6. Serum creatinine ≤1.5 x the ULN and a calculated creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method.
7. Negative serum or urine pregnancy test within 3 days prior to start of study treatment.
8. 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.
9. Predicted life expectancy ≥12 weeks.


1. 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.
2. 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.


1. 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.
2. Ovarian cancer confirmed BRCA wild-type from a prior test.
3. 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-).
4. 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).

Exclusion Criteria

1. Any chemotherapy within 3 weeks of the first dose of AZD1775, except hormonal therapy in the refractory cohort.
2. Use of a study drug ≤21 days or 5 half-lives, whichever is shorter.
3. Major surgical procedures ≤28 days, or minor procedures ≤7 days.
4. Grade \>1 toxicity from prior therapy (except alopecia or anorexia).
5. CNS disease other than neurologically stable, treated brain metastases.
6. 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.
7. NYHA ≥ Class 2.
8. Mean resting corrected QT interval (QTc) ≥450 msec for males and ≥470 msec for females.
9. Pregnant or lactating.
10. 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Todd M. Bauer, MD

Role: PRINCIPAL_INVESTIGATOR

SCRI Development Innovations, LLC

Locations

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Research Site

Fayetteville, Arkansas, United States

Site Status

Research Site

San Francisco, California, United States

Site Status

Research Site

West Hollywood, California, United States

Site Status

Research Site

Fort Myers, Florida, United States

Site Status

Research Site

Indianapolis, Indiana, United States

Site Status

Research Site

Detroit, Michigan, United States

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Research Site

Charlotte, North Carolina, United States

Site Status

Research Site

Oklahoma City, Oklahoma, United States

Site Status

Research Site

Philadelphia, Pennsylvania, United States

Site Status

Research Site

Greenville, South Carolina, United States

Site Status

Research Site

Nashville, Tennessee, United States

Site Status

Research Site

Houston, Texas, United States

Site Status

Research Site

Milwaukee, Wisconsin, United States

Site Status

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Edmonton, Alberta, Canada

Site Status

Research Site

Vancouver, British Columbia, Canada

Site Status

Research Site

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type DERIVED
PMID: 37278879 (View on PubMed)

Other Identifiers

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REFMAL 383

Identifier Type: OTHER

Identifier Source: secondary_id

D6015C00001

Identifier Type: -

Identifier Source: org_study_id

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