Study of AZD1775 in Combination With Paclitaxel, in Advanced Gastric Adenocarcinoma Patients Harboring TP53 Mutation as a Second-line Chemotherapy

NCT02448329 | Completed Phase 2

• 1 other identifier: 2014-04-127
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single arm, single center phase II study of AZD1775 in combination with paclitaxel in patients with advanced gastric adenocarcinoma harboring TP53 mutation as a second-line chemotherapy. Patients will receive AZD 1775 plus weekly paclitaxel combination regimen. The arm is composed of 25 patients. AZD1775 225 mg BID q 12 hours (x 5 doses) administered days 1\~3 + paclitaxel 80 mg/m2 given days 1, 8 and 15 of a 28 day cycle. Tumour evaluation using Response Evaluation Criteria in Solid Tumors 1.1 will be conducted at screening every 16 weeks until objective disease progression .

Conditions

Advanced Gastric Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  8weeks

Secondary Outcomes (5)

• Duration of response

  24weeks

• Disease control rate

  8weeks

• Overall survival

  24weeks

• progression-free survival (PFS)

  24weeks

• safety and tolerability measured by Adverse Events,Vital signs,Collection of clinical chemistry/haematology parameters,ECGs

  24weeks

Study Arms (1)

AZD1775 in Combination With Paclitaxel

EXPERIMENTAL

AZD1775 225 mg BID q 12 hours (x 5 doses, 2.5 days) administered days 1\~3 Weekly paclitaxel 80 mg/m2 IV on 1, 8 and 15 of a four week l cycle is an widely used dose of paclitaxel given on this schedule in gastric adenocarcinoma patients as second-line therapy.

Drug: AZD1775; Drug: paclitaxel

Interventions

AZD1775 DRUG

AZD1775 225 mg BID q 12 hours (x5 doses, 2.5 days) administered days 1\~3

AZD1775 in Combination With Paclitaxel

paclitaxel DRUG

paclitaxel 80 mg/m2 given days 1, 8 and 15 of a 28 day cycle

AZD1775 in Combination With Paclitaxel

Eligibility Criteria

• Age: Up to 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Provision of fully informed consent prior to any study specific procedures.
• Patients must be ≥20 years of age.
• Advanced gastric adenocarcinoma (including GEJ) that has progressed during or after first line therapy.
• The 1st line regimen must have contained doublet 5-fluoropyrimidine or platinum based regimen.
• Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy containing doublet 5-fluoropyrimidine and platinum-based regimen could be considered as 1st line therapy.
• Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the 1st line therapy.
• Provision of tumor sample (from either a resection or biopsy)
• Patients with p53mutation
• Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
• Eastern Cooperative Oncology Group performance status 0-1
• Patients must have a life expectancy ≥ 3 months from proposed first dose date.
• Patients must have acceptable bone marrow, liver and renal function measured within 28 days prior to administration of study treatment as defined below:
• Haemoglobin ≥9.0 g/dL (transfusion allowed)
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• White blood cells (WBC) \> 3 x 109/L

You may not qualify if:

• More than one prior chemotherapy regimen (except for adjuvant/neoadjuvant chemotherapy with more than 6 month wash out period) for the treatment of gastric cancer in the advanced setting.
• Any previous treatment with P53 inhibitors (small molecules)
• Any previous treatment with paclitaxel
• Patients with second primary cancer, except: adequately treated non-melanoma skin cancer,curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≤5 years.
• HER2 positive patients (defined by HER2 3+ by immunohistochemistry or HER2 SISH +)
• Patients unable to swallow orally administered medication.
• Treatment with any investigational product during the last 14 days before the enrollment (or a longer period depending on the defined characteristics of the agents used).
• Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 3 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates or denusomab for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment.
• Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole,ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
• With the exception of alopecia, any ongoing toxicities (\>Common Toxicity Criteria for Adverse Effects grade 1) caused by previous cancer therapy.
• Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment.
• Resting ECG with measurable QTcB \> 480 msec on 2 or more time points within a 24hour period or family history of long QT syndrome.
• Patients with cardiac problem as follows: uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy) Left ventricular ejection fraction \<55% measured by echocardiography, Atrial fibrillation with a ventricular rate \>100 bpm on ECG at rest , Symptomatic heart failure (NYHA grade II-IV), Prior or current cardiomyopathy, Severe valvular heart disease, Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy), Acute coronary syndrome within 6 months prior to starting treatment
• Ophthalmological conditions as follows:Intra-ocular pressure \>21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure), Current or past history of central serous retinopathy or retinal vein occlusion
• Female patients who are breast-feeding or child-bearing

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical center

Seoul, 135-710, South Korea

Location

MeSH Terms

Interventions

adavosertib; Paclitaxel

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jee yun Lee, MD,Ph.D.

  Samsung Medical Center,Seoul,Korea

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD,PhD

Study Record Dates

• First Submitted: May 13, 2015
• First Posted: May 19, 2015
• Study Start: January 14, 2015
• Primary Completion: December 1, 2019
• Study Completion: April 19, 2021
• Last Updated: June 15, 2022

Record last verified: 2022-06

Locations

KR (1)