Locally Advanced Solid TumoursPhase 1NCT02610075
Phase Ib Study to Determine MTD of AZD1775 Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumours.
A Phase 1 study testing AZD1775 in people with Locally Advanced Solid Tumours and Metastatic Solid Tumours, run by AstraZeneca at 3 sites in United States.
Trial summary
This Phase Ib study will identify the Maximum Tolerated Dose (MTD) of AZD1775 monotherapy when administered orally once daily (QD) or two times per day (BID) on Days 1 to 5 followed by 9 days of rest in 14-day cycles, or QD on a 5/2 dosing schedule (5 days on, followed by 2 days rest) in 21-day cycles in patients with… Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Locally Advanced Solid Tumours, Metastatic Solid Tumours, Ovarian Cancer
- What is being tested?
- AZD1775
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 3 sitesUnited States
- Study dates
- 1 Dec 2015to 26 Apr 2018
- 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
- Prior palliative radiation completed ≥ 7 days prior to the start of AZD1775 and recovered from any acute adverse effects.
- ECOG PS score 0 or 1.
- Baseline laboratory values:
- ANC ≥1500/μL
- Hemoglobin (HgB) ≥9 g/dL
- Platelets ≥100,000/μL
Show all 15Show fewer
- ALT and AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases.
- Serum bilirubin WNL or ≤1.5 x 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 ULN, or measured creatinine clearance ≥45 mL/min.
- Females who are not of child-bearing potential and fertile females of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 3 days prior to, and on the day of starting study treatment.
- Males willing to use at least one medically acceptable form of contraception for duration of study and for 3 months after treatment stops.
- Predicted life expectancy ≥12 wks.
- Age ≥18
- 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.
- Measurable or non-measurable disease according to RECIST v1.1.
Who cannot join
- Use of a treatment drug 21 days or 5 half-lives (whichever is shorter) prior to AZD1775. For drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the prior treatment and administration of AZD1775 treatment is required.
- Use of an investigational drug during the past 30 days or 5 half-lives (whichever is longer) prior to first dose of study treatment.
- Major surgical procedures ≤28 days of beginning study treatment, or minor surgical procedures ≤7 days.
- Grade >1 toxicity from prior therapy (except alopecia or anorexia).
- Inability to swallow oral medications.
- Palliative radiation therapy completed ≤7 days prior to start of study drug.
Show all 19Show fewer
- Known malignant CNS disease other than neurologically stable, treated brain metastases.
- Rx or non-Rx drugs or 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 2 weeks prior to dosing and withheld until 2 weeks after the last dose of study drug.
- Patients should stop using herbal medications 7 days prior to first dose of study treatment.
- Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥ Class 2.
- Unstable angina pectoris
- Congestive heart failure
- Acute myocardial infarction
- Conduction abnormality not controlled with pacemaker or medication
- Significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)
- History of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected.
- 11. Mean resting QTc interval >470 msec (as calculated per institutional standards) at study entry obtained from 3 ECGs within 5 minutes or congenital long QT syndrome.
- 12. Pregnant or lactating. 13. Serious active infection at the time of study entry, or another serious underlying medical condition that would impair the ability of the patient to receive study treatment.
- 14. Presence of other active invasive cancers. 15. Psychological, familial, sociological, or geographical conditions that do not permit compliance with protocol.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Research Site
Denver, Colorado, 80218
Research Site
Nashville, Tennessee, 32705
Research Site
Scottsdale, Arizona, 85258
About this study
Official title: A Phase Ib Study to Determine the Maximum Tolerated Dose (MTD) of AZD1775 Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumours.
This Phase Ib study will identify the Maximum Tolerated Dose (MTD) of AZD1775 monotherapy when administered orally once daily (QD) or two times per day (BID) on Days 1 to 5 followed by 9 days of rest in 14-day cycles, or QD on a 5/2 dosing schedule (5 days on, followed by 2 days rest) in 21-day cycles in patients with locally advanced or metastatic solid tumours. Alternative treatment schedules may be explored if preliminary data suggest these would be more appropriate.
The effect of food on single dose PK of AZD1775 will be assessed in 12 patients. In this sub-study, patients will receive a single oral dose of AZD1775 with 240 mL of water, once in the fasted state and once following a high-fat meal.
Read the detailed description
This study will attempt to determine the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of AZD1775 monotherapy when administered orally once daily (QD) or two times per day (BID) on Days 1 to 5 followed by 9 days of rest in 14-day cycles, or QD on a 5/2 dosing schedule (5 days on, followed by 2 days rest) in 21-day cycles in patients with locally advanced or metastatic solid tumours. Both the QD 5/9 and 5/2 dosing schedules will run in parallel. An evaluation will be made after the second QD cohort has been completed to determine whether to proceed with one or both dosing schedules.
The AZD1775 MTD will be determined through dose-escalation using a 3+3 cohort design. If less than one-third of evaluable patients in a given cohort (0 of 3 patients or 1 of 6 patients) experiences a Dose-Limiting Toxicity (DLT); escalation may proceed to the next higher dose level. If one of the first 3 patients enrolled in a given cohort experiences a DLT, 3 additional patents will be enrolled in that cohort. If a DLT is observed in one-third or more of patients, the dose at which this occurs will be considered not tolerated and the MTD will have been exceeded. The highest dose level(s) at which less than one-third of patients (0 of 3 patients or 1 of 6 patients) experiences a DLT will be declared the MTD. Up to 6 patients will be enrolled in each cohort. Dose escalation will continue until identification of the MTD or Sponsor termination of the study.
A maximum of 10 dose escalations are anticipated in the determination of MTD. Approximately 6 subjects may be added to replace non-evaluable patients. Therefore, a total of 66 patients are expected to be treated.
Dose-limiting toxicities will be evaluated during Cycles 1 and 2 of treatment. If appropriate the DLT observation period can be expanded by up to 2 weeks in case of treatment delay due to study drug-related adverse events. Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Patients must complete Cycle 1 and Cycle 2 safety evaluations which will conclude on Cycle 3 Day 1, and must receive at least 80% of the planned dose to be considered evaluable. Patients receiving less than 80% of Cycle 1 and Cycle 2 dose (28 days) will be replaced unless they experienced a confirmed DLT.
The patient population used to determine the MTD will consist of patients who have met the minimum safety evaluation requirements of the study, and/or who have experienced a DLT in Cycle 1 or Cycle 2. Minimum safety requirements will be met if during Cycle 1 and Cycle 2 of treatment the patient receives a minimum of 80% of treatment doses of AZD1775, completes the safety evaluations, and is observed for at least 28 days. Patients who do not meet these minimum safety evaluation and treatment requirements and whom do not experience a DLT will be replaced.
Patients will be allowed to continue treatment with AZD1775 until evidence of disease progression, unacceptable toxicity, or other discontinuation criterion has occurred.
- Being tested
- AZD1775
- Keywords
- AZD1775, Metastatic solid tumors, Ovarian cancer
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD1775Drug
All patients will receive intervention with AZD1775 orally. Patients will continue to receive treatment with AZD1775 until disease progression, intolerable toxicity, or discontinuation criteria are met.
| Study group | Role | What they receive |
|---|---|---|
| AZD1775 | Experimental | This is a single-arm study in which all patients will receive AZD1775 orally. Patients will continue to receive treatment with AZD1775 until disease progression, intolerable toxicity, or discontinuation criteria are met. Receives: Drug: AZD1775 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of dose-limiting toxicities (DLTs) associated with AZD1775 monotherapy administered once daily (QD) in 14 day cycles (5 days on, followed by 9 days rest) in patients with locally advanced or metastatic solid tumours.
The MTD will be determined through dose-escalation using a 3+3 cohort design. If less than one-third of evaluable patients in a given cohort (0 of 3 patients or 1 of 6 patients) experiences a DLT; escalation may proceed to the next higher dose level. If one of the first 3 patients enrolled in a given cohort experiences a dose-limiting toxicity (DLT), at least 3 additional patents will be enrolled in that cohort. If a DLT is observed in one-third or more of patients, the dose at which this occurs will be considered not tolerated and the MTD will have been exceeded. The highest dose level(s) at which less than one-third of patients (0 of 3 patients or 1 of 6 patients) experiences a DLT will be declared the MTD.
Measured: Dose-limiting toxicities will be evaluated during the first 2 cycles (28 days) of AZD1775 monotherapy treatment.
The incidence of dose-limiting toxicities (DLTs) associated with AZD1775 monotherapy administered once daily (QD) in 21-day cycles (5 days on, followed by 2 days rest) in patients with locally advanced or metastatic solid tumours.
The MTD will be determined through dose-escalation using a 3+3 cohort design. If less than one-third of evaluable patients in a given cohort (0 of 3 patients or 1 of 6 patients) experiences a DLT; escalation may proceed to the next higher dose level. If one of the first 3 patients enrolled in a given cohort experiences a dose-limiting toxicity (DLT), at least 3 additional patents will be enrolled in that cohort. If a DLT is observed in one-third or more of patients, the dose at which this occurs will be considered not tolerated and the MTD will have been exceeded. The highest dose level(s) at which less than one-third of patients (0 of 3 patients or 1 of 6 patients) experiences a DLT will be declared the MTD.
Measured: Dose-limiting toxicities will be evaluated during the first cycle (21 days) of AZD1775 monotherapy treatment.
The incidence of dose-limiting toxicities (DLTs) associated with AZD1775 monotherapy administered twice daily (BID) in 14-day cycles (5 days on, followed by 9 days rest) in patients with locally advanced or metastatic solid tumours.
The MTD will be determined through dose-escalation using a 3+3 cohort design. If less than one-third of evaluable patients in a given cohort (0 of 3 patients or 1 of 6 patients) experiences a DLT; escalation may proceed to the next higher dose level. If one of the first 3 patients enrolled in a given cohort experiences a dose-limiting toxicity (DLT), at least 3 additional patents will be enrolled in that cohort. If a DLT is observed in one-third or more of patients, the dose at which this occurs will be considered not tolerated and the MTD will have been exceeded. The highest dose level(s) at which less than one-third of patients (0 of 3 patients or 1 of 6 patients) experiences a DLT will be declared the MTD.
Measured: Dose-limiting toxicities will be evaluated during the first 2 cycles (28 days) of AZD1775 monotherapy treatment.
Secondary outcomes (5)
Plasma concentration of AZD1775 in fasted condition
Blood samples for determination of AZD1775 concentration will be collected during dose escalation and dose expansion.
Measured: Samples for AZD1775 PK analysis (fasted) will be taken on Cycle 1 Day 1 predose & 2 hr postdose, Cycle 1, Day 5 pre-dose & 1, 2, 4, 6, 8, & 10 hr post-dose. Samples will also be collected on Cycle 5, Day 3, 4, or 5 pre-dose & pre-dose every 3-5 Cycles.
Plasma concentration of AZD1775 when dosed with a high fat meal.
Blood samples for determination of AZD1775 concentration will be collected during dose escalation and dose expansion.
Measured: Samples for AZD1775 PK food effect analysis will be taken 4 hours after dosing on Cycle 2 Day 1. Subjects will fast for 10 hours prior to dose and for 4 hours post-dose except for the high-fat meal 30 minutes post-dose.
The incidence of treatment-emergent adverse events (TEAEs) in patients with locally advanced or metastatic solid tumours.
Treatment-emergent adverse events will be assessed by physical examinations, ECOG performance status, complete blood count (CBC) with differential and platelets, clinical chemistry and haematology, triplicate 12-lead ECG, changes in vital signs, and patient reported symptoms.
Measured: 6 months
Best objective response (OR) to treatment will be assessed by dose level cohort according to RECIST v1.1 in patients with locally advanced or metastatic solid tumours.
RECIST v1.1 criteria will be used to assess response to treatment. Tumour imaging studies will be repeated every 4 cycles (8 weeks) to assess response until objective disease progression as defined by RECIST v1.1 or withdrawal from study.
Categorisation of objective tumour response assessment will be based on the RECIST v1.1 criteria of response: Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD). Target lesion progression will be calculated in comparison to when the tumour burden was at a minimum. In the absence of progression, tumour response will be calculated in comparison to the baseline tumour measurements obtained before starting treatment.
Measured: 8 weeks
The incidence of QTc interval abnormalities in patients with locally advanced or metastatic solid tumours.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2015 (estimated)
- Study start1 Dec 2015
- Primary completion26 Apr 2018
- Study completion26 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Solid TumoursStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe 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
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gerald Falchook, MD, Principal investigator, Sarah Cannon Research Institute HealthOne, Denver, CO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02610075
- Sponsor's protocol ID
- D6015C00003
- Other IDs
- REFMAL 398
- Status last verified
- Jun 2023
- First submitted
- 17 Nov 2015
- Last updated
- 3 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Study to Determine the Maximum Tolerated Dose (MTD) of AZD1775 Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumours.
- ClinicalTrials.gov ID
- NCT02610075
- Acronym / sponsor ID
- D6015C00003
- Keywords
- AZD1775, Metastatic solid tumors, Ovarian cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 1 Dec 2015 (actual)
- Primary completion
- 26 Apr 2018 (actual)
- Study completion
- 26 Apr 2018 (actual)
- First posted
- 20 Nov 2015 (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.
This Phase Ib study will identify the Maximum Tolerated Dose (MTD) of AZD1775 monotherapy when administered orally once daily (QD) or two times per day (BID) on Days 1 to 5 followed by 9 days of rest in 14-day cycles, or QD on a 5/2 dosing schedule (5 days on, followed by 2 days rest) in 21-day cycles in patients with locally advanced or metastatic solid tumours. Alternative treatment schedules may be explored if preliminary data suggest these would be more appropriate.
The effect of food on single dose PK of AZD1775 will be assessed in 12 patients. In this sub-study, patients will receive a single oral dose of AZD1775 with 240 mL of water, once in the fasted state and once following a high-fat meal.
Detailed description
This study will attempt to determine the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of AZD1775 monotherapy when administered orally once daily (QD) or two times per day (BID) on Days 1 to 5 followed by 9 days of rest in 14-day cycles, or QD on a 5/2 dosing schedule (5 days on, followed by 2 days rest) in 21-day cycles in patients with locally advanced or metastatic solid tumours. Both the QD 5/9 and 5/2 dosing schedules will run in parallel. An evaluation will be made after the second QD cohort has been completed to determine whether to proceed with one or both dosing schedules.
The AZD1775 MTD will be determined through dose-escalation using a 3+3 cohort design. If less than one-third of evaluable patients in a given cohort (0 of 3 patients or 1 of 6 patients) experiences a Dose-Limiting Toxicity (DLT); escalation may proceed to the next higher dose level. If one of the first 3 patients enrolled in a given cohort experiences a DLT, 3 additional patents will be enrolled in that cohort. If a DLT is observed in one-third or more of patients, the dose at which this occurs will be considered not tolerated and the MTD will have been exceeded. The highest dose level(s) at which less than one-third of patients (0 of 3 patients or 1 of 6 patients) experiences a DLT will be declared the MTD. Up to 6 patients will be enrolled in each cohort. Dose escalation will continue until identification of the MTD or Sponsor termination of the study.
A maximum of 10 dose escalations are anticipated in the determination of MTD. Approximately 6 subjects may be added to replace non-evaluable patients. Therefore, a total of 66 patients are expected to be treated.
Dose-limiting toxicities will be evaluated during Cycles 1 and 2 of treatment. If appropriate the DLT observation period can be expanded by up to 2 weeks in case of treatment delay due to study drug-related adverse events. Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Patients must complete Cycle 1 and Cycle 2 safety evaluations which will conclude on Cycle 3 Day 1, and must receive at least 80% of the planned dose to be considered evaluable. Patients receiving less than 80% of Cycle 1 and Cycle 2 dose (28 days) will be replaced unless they experienced a confirmed DLT.
The patient population used to determine the MTD will consist of patients who have met the minimum safety evaluation requirements of the study, and/or who have experienced a DLT in Cycle 1 or Cycle 2. Minimum safety requirements will be met if during Cycle 1 and Cycle 2 of treatment the patient receives a minimum of 80% of treatment doses of AZD1775, completes the safety evaluations, and is observed for at least 28 days. Patients who do not meet these minimum safety evaluation and treatment requirements and whom do not experience a DLT will be replaced.
Patients will be allowed to continue treatment with AZD1775 until evidence of disease progression, unacceptable toxicity, or other discontinuation criterion has occurred.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AZD1775 | Experimental | Drug: AZD1775This is a single-arm study in which all patients will receive AZD1775 orally. Patients will continue to receive treatment with AZD1775 until disease progression, intolerable toxicity, or discontinuation criteria are met. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Prior palliative radiation completed ≥ 7 days prior to the start of AZD1775 and recovered from any acute adverse effects.
- ECOG PS score 0 or 1.
- Baseline laboratory values:
- Females who are not of child-bearing potential and fertile females of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 3 days prior to, and on the day of starting study treatment.
- Males willing to use at least one medically acceptable form of contraception for duration of study and for 3 months after treatment stops.
Key exclusion criteria (19 listed)
- Use of a treatment drug 21 days or 5 half-lives (whichever is shorter) prior to AZD1775. For drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the prior treatment and administration of AZD1775 treatment is required.
- Use of an investigational drug during the past 30 days or 5 half-lives (whichever is longer) prior to first dose of study treatment.
- Major surgical procedures ≤28 days of beginning study treatment, or minor surgical procedures ≤7 days.
- Grade >1 toxicity from prior therapy (except alopecia or anorexia).
- Inability to swallow oral medications.
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 |
|---|---|---|
| AZD1775All patients will receive intervention with AZD1775 orally. Patients will continue to receive treatment with AZD1775 until disease progression, intolerable toxicity, or discontinuation criteria are met. | Drug | AZD1775 |
Primary outcome
The incidence of dose-limiting toxicities (DLTs) associated with AZD1775 monotherapy administered once daily (QD) in 14 day cycles (5 days on, followed by 9 days rest) in patients with locally advanced or metastatic solid tumours.
Time frame: Dose-limiting toxicities will be evaluated during the first 2 cycles (28 days) of AZD1775 monotherapy treatment.
The MTD will be determined through dose-escalation using a 3+3 cohort design. If less than one-third of evaluable patients in a given cohort (0 of 3 patients or 1 of 6 patients) experiences a DLT; escalation may proceed to the next higher dose level. If one of the first 3 patients enrolled in a given cohort experiences a dose-limiting toxicity (DLT), at least 3 additional patents will be enrolled in that cohort. If a DLT is observed in one-third or more of patients, the dose at which this occurs will be considered not tolerated and the MTD will have been exceeded. The highest dose level(s) at which less than one-third of patients (0 of 3 patients or 1 of 6 patients) experiences a DLT will be declared the MTD.
The incidence of dose-limiting toxicities (DLTs) associated with AZD1775 monotherapy administered once daily (QD) in 21-day cycles (5 days on, followed by 2 days rest) in patients with locally advanced or metastatic solid tumours.
Time frame: Dose-limiting toxicities will be evaluated during the first cycle (21 days) of AZD1775 monotherapy treatment.
The MTD will be determined through dose-escalation using a 3+3 cohort design. If less than one-third of evaluable patients in a given cohort (0 of 3 patients or 1 of 6 patients) experiences a DLT; escalation may proceed to the next higher dose level. If one of the first 3 patients enrolled in a given cohort experiences a dose-limiting toxicity (DLT), at least 3 additional patents will be enrolled in that cohort. If a DLT is observed in one-third or more of patients, the dose at which this occurs will be considered not tolerated and the MTD will have been exceeded. The highest dose level(s) at which less than one-third of patients (0 of 3 patients or 1 of 6 patients) experiences a DLT will be declared the MTD.
The incidence of dose-limiting toxicities (DLTs) associated with AZD1775 monotherapy administered twice daily (BID) in 14-day cycles (5 days on, followed by 9 days rest) in patients with locally advanced or metastatic solid tumours.
Time frame: Dose-limiting toxicities will be evaluated during the first 2 cycles (28 days) of AZD1775 monotherapy treatment.
The MTD will be determined through dose-escalation using a 3+3 cohort design. If less than one-third of evaluable patients in a given cohort (0 of 3 patients or 1 of 6 patients) experiences a DLT; escalation may proceed to the next higher dose level. If one of the first 3 patients enrolled in a given cohort experiences a dose-limiting toxicity (DLT), at least 3 additional patents will be enrolled in that cohort. If a DLT is observed in one-third or more of patients, the dose at which this occurs will be considered not tolerated and the MTD will have been exceeded. The highest dose level(s) at which less than one-third of patients (0 of 3 patients or 1 of 6 patients) experiences a DLT will be declared the MTD.
5 secondary outcomes
Plasma concentration of AZD1775 in fasted condition
Time frame: Samples for AZD1775 PK analysis (fasted) will be taken on Cycle 1 Day 1 predose & 2 hr postdose, Cycle 1, Day 5 pre-dose & 1, 2, 4, 6, 8, & 10 hr post-dose. Samples will also be collected on Cycle 5, Day 3, 4, or 5 pre-dose & pre-dose every 3-5 Cycles.
Plasma concentration of AZD1775 when dosed with a high fat meal.
Time frame: Samples for AZD1775 PK food effect analysis will be taken 4 hours after dosing on Cycle 2 Day 1. Subjects will fast for 10 hours prior to dose and for 4 hours post-dose except for the high-fat meal 30 minutes post-dose.
The incidence of treatment-emergent adverse events (TEAEs) in patients with locally advanced or metastatic solid tumours.
Time frame: 6 months
Best objective response (OR) to treatment will be assessed by dose level cohort according to RECIST v1.1 in patients with locally advanced or metastatic solid tumours.
Time frame: 8 weeks
The incidence of QTc interval abnormalities in patients with locally advanced or metastatic solid tumours.
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2023.
- Related InfoLink provided by the sponsor.
Related trials for Locally Advanced Solid Tumours
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
RecruitingPhase 1
A Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of IDE574 Therapy in Adult Participants With Advanced Solid Tumors
Cancer
Active, not recruitingPhase 2
Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations
Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8
Active, not recruitingPhase 1
A Study to Evaluate the Safety, Pharmacokinetics, and Activity of RO7566802 as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors
Locally Advanced Solid Tumors, Recurrent Solid Tumors
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.
Gerald Falchook, MD principal investigator
Sarah Cannon Research Institute HealthOne, Denver, CO
3 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 AZD1775 in people with Locally Advanced Solid Tumours and Metastatic Solid Tumours, run by AstraZeneca at 3 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 15 inclusion and 19 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 3 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 toxicities (DLTs) associated with AZD1775 monotherapy administered once daily (QD) in 14 day cycles (5 days on, followed by 9 days rest) in patients with locally advanced or metastatic solid tumours. (time frame: Dose-limiting toxicities will be evaluated during the first 2 cycles (28 days) of AZD1775 monotherapy treatment.). 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?
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; AzTrials last refreshed its copy on 6 Nov 2026.