A Phase I Study of Safety, Tolerability, and PK of AZD2811 in Patients with Advanced Solid Tumors.

Study identifier:D6130C00001

ClinicalTrials.gov identifier:NCT02579226

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase I, Open-Label, Multicentre Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD2811 in Patients with Advanced Solid Tumours.

Medical condition

Advanced Solid Tumours

Phase

Phase 1

Healthy volunteers

Study drug

AZD2811

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 28 Oct 2015

Primary Completion Date: 07 Feb 2020

Study Completion Date: 03 Apr 2020

Study design

Allocation: Non-randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2021 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

Part A Dose Escalation:
1. Histological or cytological confirmation of a solid tumour and disease progression despite standard therapy(ies), or they must be intolerant to standard therapy(ies), or no standard therapy exists.
2. Patients must have received ≤3 prior chemotherapy regimens in the metastatic setting which may have included irinotecan.
Part B Dose Expansion:
1. Patients must have received at least 1 prior platinum-based systemic therapy but no more than 3 prior systemic regimens for relapsed and/or refractory SCLC.
Inclusion Criteria All Patients:
1. Measurable or non-measurable (but evaluable disease) according to RECIST v1.1.
2. Age ≥18
3. Adequate organ system functions, as outlined by a) absolute neutrophil count (ANC) ≥1.5 X 10^9/L, b) platelets ≥100 X 10^9/L, c) hemoglobin ≥9 g/dL, d) PT/PTT/INR ≤1.5 x upper limit of normal (ULN), e) total bilirubin ≤1.5 mg/dL, f) ALT and AST ≤3.0 times the ULN if no liver involvement or ≤5 times the ULN with liver involvement, g) creatinine ≤1.5 x ULN, OR calculated or measured creatinine clearance ≥50 mL/min, OR 24-hour measured urine creatinine clearance ≥50 mL/min
4. ECOG performance status 0-1.
5. Must provide an archived tissue sample for correlative testing, if available. If archived tissue is not available, patient will still be eligible for enrolment into the study.
6. Predicted life expectancy ≥12 weeks.
7. Females of child-bearing potential should be using adequate contraceptive measures from the time of screening until 6 months after study discontinuation, should not be breast feeding and must have a negative pregnancy test prior to start of dosing. Females of non-child-bearing potential must have evidence by the following criteria at screening: a) post-menopausal defined as aged > 50 and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments, b) documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not tubal ligation, c) women < 50 would be considered postmenopausal if they have been amenorrhoeic for > 12 months following cessation of all exogenous hormonal treatments, and have serum follicle-stimulating hormone and luteinizing hormone levels in the postmenopausal range.
8. Sexually active males should be willing to use barrier contraception (i.e., condoms).

Exclusion Criteria

1. Patients who have been treated with most recent radiotherapy, immunotherapy, chemotherapy or investigational drugs within ≤21 days or 5 half-lives (whichever is shorter) from enrolment (screening), and/or who have any unresolved NCI Common Terminology Criteria of Adverse Events (CTCAE) v4.03 > Grade 1 treatment-related side effect, with the exceptions of alopecia, should not be enrolled.
2. Major surgery (excluding placement of vascular access) ≤21 days from beginning of the study drug or minor surgical procedures ≤7 days. No waiting is required following implantable port and catheter placement.
3. Previous treatment with alisertib.
4. Any of the following cardiac criteria: a) Congestive heart failure (CHF) per New York Heart Association (NYHA) classification > Class II, b) Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy, c) Unstable angina or new-onset angina, d) QTcF interval >470 ms on screening ECG.
5. Active non-infectious skin disease (including any grade rash, urticarial, dermatitis, ulceration, or psoriasis, but excluding stable plaque psoriasis from the definition of active disease).
6. Patients with diarrhoea NCI CTCAE v4.03 Grade ≥2.
7. Patient has had prescription or non-prescription drugs or other products known to be strong inhibitors/inducers of CYP3A4 which cannot be discontinued prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug.
8. Any evidence of active infection, severe or uncontrolled systemic diseases including uncontrolled hypertension, active bleeding diatheses, hepatitis B, hepatitis C and human immunodeficiency virus.
9. Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 3 weeks previously and there is no evidence of central nervous system disease progression, mild neurologic symptoms, and no requirement for chronic corticosteroid therapy.
10. Treatment with haematopoietic colony-stimulating factors (e.g., G-CSF) ≤2 weeks prior to screening visit.
11. History of hypersensitivity to active or inactive excipients (e.g., PEG) of any drug in the study or drugs with similar chemical structure or class to those being investigated in the study.
12. Lactating, breastfeeding, or positive pregnancy test for female patients of child-bearing potential.
13. Concurrent conditions that in the Investigator's opinion would jeopardize compliance with the protocol.
14. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

Location

Research Site

Nashville, TN, United States, 37203

Location

Research Site

Sarasota, FL, United States, 34232

Location

Research Site

Denver, CO, United States, 80218

Location

Research Site

Houston, TX, United States, 77030

Location

Research Site

Milwaukee, WI, United States, 53226

Location

Research Site

Boston, MA, United States, 02215

Arms	Assigned Interventions
Experimental: Part A Part A dose-escalation will evaluate the safety and tolerability of AZD2811 monotherapy at increasing doses in patients with advanced solid tumours. Patients will receive AZD2811 on Days 1 and 4 of a 28-day cycle or Day 1 only in cycles of either 21 or 28 days.	Drug: AZD2811 The study will be conducted in 2 parts, dose-escalation (A) and dose-expansion (B). All patients in both parts of the study with receive AZD2811. Other Name: none
Experimental: Part B Part B will include patients with relapsed or refractory small-cell lung cancer (SCLC). Patients will receive AZD2811 monotherapy at the recommended Phase 2 dose (RP2D).	Drug: AZD2811 The study will be conducted in 2 parts, dose-escalation (A) and dose-expansion (B). All patients in both parts of the study with receive AZD2811. Other Name: none