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

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ClinicalTrials.gov Identifier: NCT03579784
Recruitment Status : Recruiting
First Posted : July 9, 2018
Last Update Posted : September 27, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Do-Youn Oh, Seoul National University Hospital

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

Condition or disease Intervention/treatment Phase
Advanced Gastric Cancer Drug: Paclitaxel Drug: Olaparib Drug: Durvalumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Biomarker-oriented Study of Durvalumab (MEDI4736) in Combination With Olaparib and Paclitaxel in Gastric Cancer
Actual Study Start Date : November 26, 2018
Estimated Primary Completion Date : April 30, 2020
Estimated Study Completion Date : April 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Stomach Cancer

Arm Intervention/treatment
Experimental: Durvalumab+Olaparib+Paclitaxel
  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
Paclitaxel 80 mg/m2 mg iv on D1, D8, D15 Every 4 weeks

Drug: Olaparib
Olaparib 150mg bid on D1-28 Every 4 weeks

Drug: Durvalumab
Durvalumab 1.5 g iv on D1 Every 4 weeks




Primary Outcome Measures :
  1. Disease control rate [ Time Frame: 8weeks ]
    The percentage of patients who have achieved CR, PR, SD based on RECIST v1.1


Secondary Outcome Measures :
  1. Overall response rate [ Time Frame: 8weeks ]
    According to RECIST 1.1, ir response criteria

  2. Progression-free survival [ Time Frame: 8weeks ]
    Time from randomization until disease progression or death

  3. Duration of response [ Time Frame: 8weeks ]
    Time from documentation of tumor response to disease progression

  4. Overall survival [ Time Frame: 8weeks ]
    Time from randomization until death from any cause

  5. Safety and tolerability as measured by number and grade of toxicity events [ Time Frame: 2weeks ]
    Overall Safety Profile by CTCAE V4.1, irAE



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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent and any locally-required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
  2. Age >= 19 years at time of study entry
  3. Histologically proven gastric cancer
  4. Unresectable or recurrent
  5. 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)
  6. Should have measurable lesion based on RECIST V1.1
  7. Without previous expose to immune-oncology agents including anti-CTLA4, anti-PD1, anti-PDL1, etc
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 , and body weight >30 kg
  9. Life expectancy of > 12weeks
  10. 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.>>
    • AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
    • Serum creatinine CL>51 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
  11. Female subjects must either be of non-reproductive potential or must have a negative serum pregnancy test upon study entry.

    Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal subjects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

  12. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Exclusion Criteria:

  1. 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
  2. Participation in another clinical study with an investigational product during the last 3weeks
  3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
  4. 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.)
  5. 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.
  6. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction
  7. 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
  8. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria

    -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.

  9. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1
  10. 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
    • Subjects with celiac disease controlled by diet alone
  11. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  12. History of primary immunodeficiency
  13. History of allogeneic organ transplant
  14. History of hypersensitivity to durvalumab or any excipient
  15. History of hypersensitivity to the combination or comparator agent
  16. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  17. History of leptomeningeal carcinomatosis
  18. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab
  19. Female subjects who are pregnant or breastfeeding or male or female subjects of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.
  20. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  21. Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.
  22. Subjects with uncontrolled seizures.
  23. Features of MDS/ AML

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03579784


Contacts
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Contact: Do-Youn Oh, MD, PhD 82-2-2072-0701 ohdoyoun@snu.ac.kr

Locations
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Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Do-Youn Oh, MD, PhD    82-2-2072-0701    ohdoyoun@snu.ac.kr   
Sponsors and Collaborators
Do-Youn Oh
AstraZeneca
Investigators
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Principal Investigator: Do-Youn Oh, MD, PhD Seoul National University Hospital

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Responsible Party: Do-Youn Oh, Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT03579784     History of Changes
Other Study ID Numbers: ESR-15-11655
First Posted: July 9, 2018    Key Record Dates
Last Update Posted: September 27, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Durvalumab
Olaparib
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immunologic Factors
Physiological Effects of Drugs
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors