AZD1775 for Advanced Solid Tumors
Public ClinicalTrials.gov record NCT01748825. Field values are reproduced from the official study page; the official ClinicalTrials.gov record remains the source of truth for eligibility, enrollment, and contact information.
Data is sourced from official ClinicalTrials.gov public API records. Always review the official ClinicalTrials.gov record for the latest information.
Official title
A Phase I Study of Single-agent AZD1775 (MK-1775), a Wee1 Inhibitor, in Patients With Advanced Refractory Solid Tumors
Brief summary
Reproduced verbatim from the official ClinicalTrials.gov record. Not medical advice.
BACKGROUND: * Wee1 is a tyrosine kinase involved in the phosphorylation and inactivation of cyclin-dependent kinase 1 (CDK1/CDC2)-bound cyclin B, resulting in G2 cell cycle arrest in response to deoxyribonucleic acid (DNA) damage to allow time for DNA repair. Recent preclinical data additionally implicates Wee1 in maintenance of genomic integrity during S phase. * Adavosertib (AZD1775) is a selective inhibitor of Wee1 kinase. Recent preclinical model data additionally show single agent anti-tumor activity in multiple cancer cell lines and tumor xenografts. * Preliminary data show AZD1775 is tolerable at lower doses in combination with chemotherapeutic agents. We propose to demonstrate single-agent activity for AZD1775. PRIMARY OBJECTIVE: * To establish the safety and tolerability of single-agent AZD1775 in patients with refractory solid tumors * To determine the pharmacokinetics of AZD1775 in patients with refractory solid tumors SECONDARY OBJECTIVES: * To determine the effect of AZD1775 on markers of DNA damage and apoptosis in tumor tissue and circulating tumor cells * To evaluate the antitumor activity of AZD1775 in patients with refractory solid tumors EXPLORATORY OBJECTIVES: -To identify tumor genomic alterations and gene expression patterns potentially associated with AZD1775 antitumor activity ELIGIBILITY: * Patients must have histologically confirmed solid tumors for which all standard therapy known to prolong survival have failed, or for which standard therapies do not exist. * No major surgery, radiation, or chemotherapy within 3 weeks or (5 half-lives, whichever is shorter) prior to entering the study. * Adequate organ function STUDY DESIGN: * This study will follow a traditional 3+3 design. * In Arm A starting at dose level 1, AZD1775 will be administered orally, twice a day (BID), for 5 doses (Day (D) 1-3) during each cycle. Starting at dose level 2 and onwards, AZD1775 will be administered orally, BID, for 5 doses for the first 2 weeks of each cycle (D1-3 and 8- 10). Each cycle is 21 days (+/- 1 day for scheduling). * Once maximum tolerated dose (MTD) is established, 6 additional patients will be enrolled at the MTD to further evaluate that dose for pharmacokinetics (PK) and pharmacodynamics (PD) endpoints. * A further expansion arm of 6 additional patients with documented tumors harboring breast cancer type 1 or 2 (BRCA)-1 or -2 mutations will also be enrolled at the MTD to further explore the safety of the agent and obtain preliminary evidence of activity in this patient population. * Based on preliminary evidence of drug activity in an alternative once-daily dosing schedule, patients without a documented BRCA mutation will be accrued to a once-daily dosing schedule Arm B, with mandatory paired tumor biopsies at the maximum tolerated single daily dose, to further evaluate PD endpoints. AZD1775 will be administered orally once daily for 5 days (D1-5 and 8-12) during weeks 1 and 2 of each 21-day cycle (+/- 1 day for scheduling). * During the escalation phase, tumor biopsies will be optional and will be evaluated for pharmacodynamic (PD) studies for evidence of Wee1 inhibition DNA damage and repair, and apoptosis (gamma H2A histone family member X (yH2AX), phosphorylated Nbs1 (pNbs1), Rad51, Rabbit polyclonal phospho-cyclin-dependent kinases (pTyr15-Cdk) and caspase 3). During the expansion phase, once MTD is reached, mandatory paired tumor biopsies will be pursued in up to 20 additional patients enrolled at the MTD to further evaluate PD endpoints.
Study identification
- NCT ID
- NCT01748825
- Recruitment status
- Completed
- Study type
- Interventional
- Phase
- Phase 1
- Enrollment
- 67 participants
Conditions and interventions
Conditions
Eligibility (public fields only)
- Age range
- 18 Years to 120 Years
- Sex
- All
- Healthy volunteers
- Healthy volunteers not accepted
This page does not interpret eligibility. Detailed inclusion and exclusion criteria are on the official ClinicalTrials.gov record.
Study timeline
- Start date
- Dec 18, 2012
- Primary completion
- May 18, 2020
- Completion
- May 18, 2020
- Last update posted
- Jul 25, 2021
2012 – 2020
United States locations
- U.S. sites
- 1
- U.S. states
- 1
- U.S. cities
- 1
| Facility | City | State | ZIP | Site status |
|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | — |
Site contact phone numbers, emails, and investigator names are intentionally not displayed here. Open the official ClinicalTrials.gov record for site contact information.
About this trial record page
- What this page shows
- Public field values for ClinicalTrials.gov record NCT01748825, including study identification, conditions, interventions, eligibility (age, sex, healthy volunteer), timeline, and U.S. site list.
- What this page does not do
- No medical advice, eligibility judgments, treatment recommendations, study quality scoring, or AI-generated medical summaries. No site contact phone numbers, emails, or investigator names.
- Where the data comes from
- Sourced from the official ClinicalTrials.gov public API. The official record is the source of truth.
- Last refresh
- Last update posted Jul 25, 2021 · Synced Sep 3, 2026
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Open the official record
The complete protocol, eligibility criteria, and contact information for NCT01748825 live on ClinicalTrials.gov.