Phase Ib Study AZD1775 in Combination With Carboplatin and Paclitaxel in Adult Asian Patients With Solid Tumours

NCT ID: NCT02341456

Last Updated: 2019-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-16
• Study Completion Date: 2018-07-09

Brief Summary

This is a phase Ib, open-label, multicentre study of AZD1775 administered orally in monotherapy and in combination with carboplatin and paclitaxel to Asian patients with advanced solid tumours.

Detailed Description

This is a phase Ib, open label, multicentre study of AZD1775 administered orally in monotherapy and in combination with carboplatin and paclitaxel in Asian patients with advanced solid tumours. The study design allows escalation or de-escalation of AZD1775 in combination with carboplatin and paclitaxel with intensive safety monitoring to ensure the safety of the patients. Approximately 12 evaluable patients will be enrolled in the dose-finding portion of this study. The total number of patients will depend upon the number of combination dose level evaluations necessary to define the recommended dose for further clinical evaluation. The proposed combination doses are : Dose level-1; Dose level 1; Dose level 2 (if Dose Level 1 tolerated). All combination doses other than Combination Dose level 1 may be subject to change by the SRC in light of emerging data. At least 3 and up to 6 evaluable patients will be required for each dose finding cohort. Once the recommended dose for further clinical evaluation is established, additional 3 to 6 patients may be enrolled to the cohort where the recommended dose has been defined to further characterise the safety, tolerability, pharmacokinetics, and efficacy profiles of AZD1775 in combination with paclitaxel and carboplatin. If this dose is subsequently found to be non-tolerated, alternative doses and/or schedules may be explored. This will be determined by the SRC.

Conditions

Advanced Solid Tumours

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AZD1775

AZD1775 will be administered orally as a single dose on Day 1 Cycle 0. Following a 5±2 days washout period, AZD1775 (5 doses BID over 2.5 days) will be taken in combination with paclitaxel and carboplatin in each 21-day cycle for 6 cycles. Following 6 cycles of combination treatment, patients may continue on AZD1775 monotherapy (5 doses BID Day 1 to Day 2.5 in each 21-day cycle) at the investigator's discretion.

Group Type: EXPERIMENTAL

AZD1775

Intervention Type: DRUG

AZD1775 is a highly selective, adenosine-triphosphate (ATP) competitive, small-molecule inhibitor of the WEE1 kinase that sensitizes tumour cells to cytotoxic agents and is being developed for the treatment of advanced solid tumours and p53 pathway deficient malignancies. Gemcitabine is a nucleoside analog used as chemotherapy.

Paclitaxel

Commercially available paclitaxel will be administered at a dosage of 175 mg/m2 as a 3-hour IV infusion on Cycle Day 1 of a 21-day cycle for 6 cycles.

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

Paclitaxel is a mitotic inhibitor used in cancer chemotherapy ; it and docetaxel represent the taxane family of drugs.

Carboplatin

Following the paclitaxel infusion, carboplatin will be administered at a dose of AUC 5 as an IV infusion on Cycle Day 1 of a 21-day cycle for 6 cycles. According to the Cancer Therapy Evaluation Program Information Letter Regarding the AUC Based Dosing of Carboplatin, the maximum carboplatin dose should not exceed the target AUC (mg\*min/mL)\*150 mL/min, but it may be less (Ivy et al 2010). For this study, the maximum dose of carboplatin cannot exceed a total dose of 750 mg.

Group Type: EXPERIMENTAL

carboplatin

Intervention Type: DRUG

Carboplatin is a chemotherapy drug used against some forms of cancer (mainly ovarian carcinoma, lung, head and neck cancers as well as endometrial, esophageal, bladder, breast and cervical; central nervous system or germ cell tumors; osteogenic sarcoma, and as preparation for a stem cell or bone marrow transplant.).

Interventions

AZD1775

AZD1775 is a highly selective, adenosine-triphosphate (ATP) competitive, small-molecule inhibitor of the WEE1 kinase that sensitizes tumour cells to cytotoxic agents and is being developed for the treatment of advanced solid tumours and p53 pathway deficient malignancies. Gemcitabine is a nucleoside analog used as chemotherapy.

Intervention Type: DRUG

Paclitaxel

Paclitaxel is a mitotic inhibitor used in cancer chemotherapy ; it and docetaxel represent the taxane family of drugs.

Intervention Type: DRUG

carboplatin

Carboplatin is a chemotherapy drug used against some forms of cancer (mainly ovarian carcinoma, lung, head and neck cancers as well as endometrial, esophageal, bladder, breast and cervical; central nervous system or germ cell tumors; osteogenic sarcoma, and as preparation for a stem cell or bone marrow transplant.).

Intervention Type: DRUG

Other Intervention Names

MK1775

Eligibility Criteria

Inclusion Criteria

• Histological or cytological confirmation of a locally advanced or metastatic solid tumour, excluding lymphoma, that failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist.
• At least 1 measureable lesion that can be accurately assessed at baseline by computerised tomography (CT) or magnetic resonance imaging (MRI) for solid tumours assessed using RECIST v1.1.
• World Health Organisation performance status 0 to 1 with no deterioration over the previous 2 weeks and a minimum life expectancy of ≥12 weeks.

Exclusion Criteria

• Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days (if investigational agent does not have well characterised PK profile) or 5 × half-lives of the first dose of study treatment
• Patient has had prescription or non-prescription drugs or other products (ie, grapefruit juice) known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors or inducers of CYP3A4, which cannot be discontinued 2 weeks before Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug. Co-administration of aprepitant during this study is prohibited.
• AZD1775 is an inhibitor of breast cancer resistance protein (BCRP). The use of statins including Atorvastatin which are substrates for BCRP are therefore prohibited and patients should be moved on to non-BCRP alternatives.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dr. Paul De Souza, MD

Role: PRINCIPAL_INVESTIGATOR

Liverpool Hospital, New South Wales

Dr. Jason Lickliter, MD

Role: PRINCIPAL_INVESTIGATOR

Nucleus Network Limited, Victoria

Dr. Noboru Yamamoto, MD

Role: PRINCIPAL_INVESTIGATOR

NCC Hospital

Dr Toshihiko Doi, MD

Role: PRINCIPAL_INVESTIGATOR

NCC Hospital (East)

Prof Yung Ju Bang

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital

Prof Sang Prof Sang

Role: PRINCIPAL_INVESTIGATOR

Asan Medical Centre

Prof Keunchil Park

Role: PRINCIPAL_INVESTIGATOR

Samsung Medical Centre

Locations

Research Site

Liverpool, , Australia

Research Site

Melbourne, , Australia

Research Site

Kashiwa, , Japan

Research Site

Sapporo, , Japan

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Countries

Australia; Japan; South Korea

Other Identifiers

D6011C00003

Identifier Type: -

Identifier Source: org_study_id