Biomarker-oriented Study of Durvalumab (MEDI4736) in Combination With Olaparib and Paclitaxel in Gastric Cancer

NCT03579784 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: ESR-15-11655
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

\<Research Hypothesis\> The dynamics of immune systems by Olaparib and its changes by combination with immune-oncology agents will be uncovered. The combination of Olaparib with Durvalumab with paclitaxel is tolerable and efficacious in gastric cancer. \<Objectives\> Primary Objectives: To assess the effect of Durvalumab in combination with olaparib and paclitaxel on DCR (Disease control rate) in gastric cancer patients

• Disease control rate (based on RECIST v1.1) Secondary Objective(s):
• Efficacy: overall response rate (RECIST 1.1, ir response), progression-free survival, duration of response, overall survival, overall survival at 6 month, overall survival at 1 year, EORTC QLQ-C30,
• Safety: toxicity (CTCAE V4.1), irAE

Conditions

Advanced Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• Disease control rate

  The percentage of patients who have achieved CR, PR, SD based on RECIST v1.1

  8weeks

Secondary Outcomes (5)

• Overall response rate

  8weeks

• Progression-free survival

  8weeks

• Duration of response

  8weeks

• Overall survival

  8weeks

• Safety and tolerability as measured by number and grade of toxicity events

  2weeks

Study Arms (1)

Durvalumab+Olaparib+Paclitaxel

EXPERIMENTAL

1. st cycle : Paclitaxel+Olaparib * Olaparib 150mg bid on D1-28 * Paclitaxel 80 mg/m2 mg iv on D1, D8, D15 2. nd cycle and thereafter: Durvalumab+Olaparib+Paclitaxel : * Olaparib 150mg bid on D1-28 * Durvalumab 1.5 g iv on D1 * Paclitaxel 80 mg/m2 mg iv on D1, D8, D15 Every 4 weeks During first 4 weeks, palictaxel/olaparib dual combination will be used. Since 2nd cycle, palictaxel/olaparib/Durvalumab combination will be used.

Drug: Paclitaxel; Drug: Olaparib; Drug: Durvalumab

Interventions

Paclitaxel DRUG

Paclitaxel 80 mg/m2 mg iv on D1, D8, D15 Every 4 weeks

Durvalumab+Olaparib+Paclitaxel

Olaparib DRUG

Olaparib 150mg bid on D1-28 Every 4 weeks

Durvalumab+Olaparib+Paclitaxel

Durvalumab DRUG

Durvalumab 1.5 g iv on D1 Every 4 weeks

Durvalumab+Olaparib+Paclitaxel

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and any locally-required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Age \>= 19 years at time of study entry
• Histologically proven gastric cancer
• Unresectable or recurrent
• Previous exposure to 1 palliative chemotherapy for their unresectable or recurrent cancer (Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy containing 5-Fluoropyrimidine monotherapy or 5-fluoropyrimidine and platinum based regimen is considered as first-line therapy)
• Should have measurable lesion based on RECIST V1.1
• Without previous expose to immune-oncology agents including anti-CTLA4, anti-PD1, anti-PDL1, etc
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 , and body weight \>30 kg
• Life expectancy of \> 12weeks
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥ 10.0 g/dL without transfusion within 28 days
• No features of MDS/AML
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 per mm3)
• Platelet count ≥ 100 x 109/L (\>100,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). \<\<This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.\>\>

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)Previous enrollment or randomization in the present study
• Participation in another clinical study with an investigational product during the last 3weeks
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 28 days prior to the first dose of study drug (14 days prior to the first dose of study drug for subjects who have received prior TKIs \[e.g., erlotinib, gefitinib and crizotinib\] and within 6 weeks for nitrosourea or mitomycin C). (If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period may be required.)
• Brain metastases or spinal cord compression unless the patient is stable (asymptomatic; no evidence of new or emerging brain metastases; and stable and off steroids for at least 14 days prior to start of study treatment). Following radiotherapy and/or surgery of the brain metastases subjects must wait 4 weeks following the intervention and before randomisation with imaging to confirm stability.
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction
• Current or prior use of immunosuppressive medication within 14days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
• Subjects with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Subjects with vitiligo or alopecia
• Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Subjects without active disease in the last 5 years may be included but only after consultation with the study physician

Sponsors & Collaborators

• Do-Youn Oh: lead
• AstraZeneca: collaborator

Study Sites (1)

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

MeSH Terms

Interventions

Paclitaxel; olaparib; durvalumab

Intervention Hierarchy (Ancestors)

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

Study Officials

• Do-Youn Oh, MD, PhD

  Seoul National University Hospital

  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: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 19, 2018
• First Posted: July 9, 2018
• Study Start: November 26, 2018
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: April 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)