Clinical Trials /

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

NCT02482311

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Fallopian Tube Carcinoma
  • Malignant Solid Tumor
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: D6015C00001
  • SECONDARY ID: REFMAL 383
  • NCT ID: NCT02482311

Conditions

  • Ovarian Cancer, TNBC, SCLC, Other Solid Tumours

Interventions

DrugSynonymsArms
AZD 1775AZD1775

Purpose

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

      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).
    

Trial Arms

NameTypeDescriptionInterventions
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.
  • AZD 1775

Eligibility Criteria

        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.

        Inclusion Criteria Specific for Part A:

          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.

        Inclusion Criteria Specific for Part B:

          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.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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)
Safety Issue:
Description:The AZD1775 dose is considered safe and tolerable if ≤ 1 of 6 patients experiences a DLT.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, projected 12 months.
Safety Issue:
Description:The proportion of patients achieving a complete or partial tumour response (CR or PR) according to RECIST 1.1 criteria.
Measure:Disease Control Rate (DCR)
Time Frame:Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, projected 12 months
Safety Issue:
Description:The proportion of patients achieving a complete response (CR) or partial response (PR), or stable disease (SD) according to RECIST v1.1 criteria
Measure:Duration of Response (DoR)
Time Frame:Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, projected 12 months
Safety Issue:
Description:The time from first documented tumor response until the date of documented progression or death from any cause.
Measure:Progression Free Survival (PFS)
Time Frame:Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, project 12 months.
Safety Issue:
Description: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.
Measure:PK profile: Plasma concentrations of AZD1775 and PK parameters (Cmax, C8hr, tmax, AUC, tlast, t½λz)
Time Frame: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
Safety Issue:
Description:Blood samples will be collected at various timepoints post-dosing
Measure:QTc prolongation
Time Frame: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.
Safety Issue:
Description:ECGs will be obtained at various timepoints

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • AZD1775
  • Ovarian cancer (BRCA1/2 mutation)
  • Ovarian cancer (PARP-failure)
  • Triple negative breast cancer (TNBC)
  • Small-cell lung cancer (SCLC)
  • Solid tumours

Last Updated

December 6, 2017