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

NCT02341456 | Completed Phase 1 Results

• 1 other identifier: D6011C00003
• Study Type: interventional
• Target: 19
• Locations: 3 countries
• Sites: 7

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.

Conditions

Advanced Solid Tumours

Outcome Measures

Primary Outcomes (6)

• Number of Patients With Treatment-Emergent Adverse Events

  The number of patients with treatment-emergent adverse events was analyzed on the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug.

  Up to 21 days (1 Cycle)

• Number of Treatment-Emergent Adverse Events (TEAE)

  The number of treatment-emergent adverse events was counted in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug.

  Up to 21 days (1 Cycle)

• Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term

  The number of patients with TEAEs during AZD1775 Monotherapy Cycle was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug.

  Up to 1 week

• Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term

  The number of patients with clinically important changes in haematology and coagulation TEAEs was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug.

  Up to 21 days (1 Cycle)

• Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term

  The number of patients with clinically important changes in clinical chemistry TEAEs was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug.

  Up to 21 days (1 Cycle)

• Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term

  The number of patients with clinically important changes in vital sign TEAEs was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug.

  Up to 21 days (1 Cycle)

Secondary Outcomes (33)

• Best Overall Response

  Up to 18 months

• Number of Patients With an Objective Response

  Up to 18 months

• Percentage of Patients With an Objective Response

  Up to 18 months

• Number of Patients With Clinical Benefit

  Up to 18 months

• Percentage of Patients With Clinical Benefit

  Up to 18 months

Study Arms (3)

AZD1775

EXPERIMENTAL

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.

Drug: AZD1775

Paclitaxel

EXPERIMENTAL

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.

Drug: Paclitaxel

Carboplatin

EXPERIMENTAL

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.

Drug: carboplatin

Interventions

AZD1775 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.

Also known as: MK1775

AZD1775

Paclitaxel DRUG

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

Paclitaxel

carboplatin 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.).

Carboplatin

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (7)

Research Site

Liverpool, 2170, Australia

Location

Research Site

Melbourne, 3004, Australia

Location

Research Site

Kashiwa, 277-8577, Japan

Location

Research Site

Sapporo, 003-0804, Japan

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Seoul, 05505, South Korea

Location

Research Site

Seoul, 135-710, South Korea

Location

MeSH Terms

Interventions

adavosertib; Paclitaxel; Carboplatin

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Limitations and Caveats

In the secondary outcome measure Duration of Response for which data are reported as weeks (95% CI) several instances occurred where the 95% CI could not be calculated.

Results Point of Contact

• Title: Lone Ottesen
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

1-877-240-9479

Study Officials

• Dr. Paul De Souza, MD

  Liverpool Hospital, New South Wales

  PRINCIPAL INVESTIGATOR

• Dr. Jason Lickliter, MD

  Nucleus Network Limited, Victoria

  PRINCIPAL INVESTIGATOR

• Dr. Noboru Yamamoto, MD

  NCC Hospital

  PRINCIPAL INVESTIGATOR

• Dr Toshihiko Doi, MD

  NCC Hospital (East)

  PRINCIPAL INVESTIGATOR

• Prof Yung Ju Bang

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

• Prof Sang Prof Sang

  Asan Medical Centre

  PRINCIPAL INVESTIGATOR

• Prof Keunchil Park

  Samsung Medical Centre

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2015
• First Posted: January 19, 2015
• Study Start: January 16, 2015
• Primary Completion: December 14, 2016
• Study Completion: July 9, 2018
• Last Updated: March 25, 2019
• Results First Posted: March 25, 2019

Record last verified: 2019-03

Locations

AU (2); JP (2); KR (3)