Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    CAURAL
Previous Study | Return to List | Next Study

Study of AZD9291 Plus MEDI4736 Versus AZD9291 Monotherapy in NSCLC After Previous EGFR TKI Therapy in T790M Mutation Positive Tumours (CAURAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02454933
Recruitment Status : Active, not recruiting
First Posted : May 27, 2015
Results First Posted : August 10, 2018
Last Update Posted : June 11, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
A Phase III, Multi-Centre, Open Label, Randomized Study to Assess the Efficacy and Safety of AZD9291 in Combination with MEDI4736 versus AZD9291 Monotherapy in patients with Locally Advanced or Metastatic Epidermal Growth Factor Receptor T790M mutation-positive Non-Small Cell Lung Cancer who have received Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy

Condition or disease Intervention/treatment Phase
Locally Advanced or Metastatic EGFR T790M+ NSCLC Drug: AZD9291 Drug: MEDI4736 Phase 3

Detailed Description:

This a phase III, Multi Centre, Open Label, Randomized, Study to Assess the Efficacy and Safety of AZD9291 (80 mg, orally, once daily) in Combination with MEDI4736 (10 mg/kg (IV) infusion q2w) versus AZD9291 Monotherapy (80 mg, orally, once daily) in patients with a confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) T790M mutation positive NSCLC, who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent. The randomization will be stratified by previous lines of treatment (2nd or 3rd+) and ethnicity (Asian or Non-Asian). A mandatory biopsy will be needed for central testing of T790M mutation status following confirmed disease progression on the most recent treatment regimen. The primary objective of the study is To investigate the safety and tolerability profile of AZD9291 in combination with MEDI4736.

350 patients were originally planned to be evaluated across the two below populations. The recruitment was stopped due to new information on safety of the combination, received from another trial in similar patient population

  1. 2nd line: patients who have progressed following an approved first-line EGFR-TKI treatment but who have not received further treatment.
  2. 3rd line or higher: patients who have progressed following prior therapy with an approved EGFR-TKI and an additional anti-cancer treatment. Patients may have also received additional lines of treatment.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Multi-Centre, Open Label, Randomized Study to Assess the Efficacy and Safety of AZD9291 in Combination With MEDI4736 Versus AZD9291 Monotherapy in Patients With Locally Advanced or Metastatic Epidermal Growth Factor Receptor T790M Mutation-positive Non-Small Cell Lung Cancer Who Have Received Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy (CAURAL)
Actual Study Start Date : July 15, 2015
Actual Primary Completion Date : August 21, 2017
Estimated Study Completion Date : December 20, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: MEDI4736 & AZD9291 Combination
10mg/kg q2w (IV) infusion & once daily tablet 80 mg
Drug: AZD9291
Once daily tablet 80 mg

Drug: MEDI4736
10mg/kg q2w (IV) infusion

Experimental: AZD9291 Monotherapy
Once daily tablet 80 mg
Drug: AZD9291
Once daily tablet 80 mg




Primary Outcome Measures :
  1. Number of Subjects With Adverse Events (AEs) as a Measure of the Safety and Tolerability of Osimertinib in Combination With Durvalumab [ Time Frame: From Baseline up to 3 months after the last dose (up to 24 months). ]
    As a measure of the safety and tolerability of osimertinib in combination with durvalumab the number of subjects who experienced any treatment emergent AE (TEAE), any causally related AE, any serious AE (SAE), and any causally related SAE are presented.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged at least 18 years. Japan patients aged at least 20 years.
  • Locally advanced/metastatic NSCLC, not amenable to curative surgery or radiotherapy
  • Confirmation from a previous archival sample that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity
  • Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI. Additional other lines of therapy may have been given. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study.
  • Patients must have central lab confirmation of tumour T790M status from a biopsy taken after disease progression on the most recent treatment regimen. Only patients with T790M+ will be included in the study
  • At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline as ≥ 10mm in the longest diameter (except lymph nodes which must have short axis ≥ 15mm) with computerised tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements
  • World Health Organisation (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks
  • Females of child-bearing potential using contraception; negative pregnancy test

Exclusion Criteria:

  • Treatment with an EGFR-TKI within 5x half-life of study entry; any cytotoxic chemotherapy, investigational agents or other anticancer drugs within 14 days of study entry; current treatment with potent inhibitors/inducers of cytochrome P450 3A4 (CYP3A4); previous treatment with AZD9291 (or other agents specifically targeted against EGFR T790M mutation positive NSCLC); Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months of starting 1st EGFR TKI treatment; prior exposure to immune-mediated therapy including, but not limited to, other anti cytotoxic T-lymphocyte-associated antigen 4 (anti CTLA-4), anti- programmed cell death 1 (anti-PD-1), anti- programmed cell death ligand 1 (anti-PD-L1), and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines; radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks; major surgery within 4 weeks;
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736 (excluding intranasal, inhaled, topical steroids, or local steroid injections)
  • Unresolved toxicities from prior therapy
  • History of active primary immunodeficiency
  • Unstable brain metastases or spinal cord compression
  • Severe/uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant, bleeding diatheses or infection
  • Cardiac disease
  • Ophthalmological conditions
  • Refractory nausea/vomiting, chronic gastrointestinal diseases or bowel resection
  • Past history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
  • History of another primary malignancy
  • Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment
  • History of organ transplant that requires use of immunosuppressive medications
  • Known history of tuberculosis
  • Receipt of live, attenuated vaccine within 30 days prior to the first dose of MEDI4736
  • Inadequate bone marrow reserve or organ function

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): NCT02454933


Locations
Layout table for location information
Canada, Ontario
Research Site
Toronto, Ontario, Canada, M5G 2M9
Korea, Republic of
Research Site
Busan, Korea, Republic of, 47392
Research Site
Daegu, Korea, Republic of, 42601
Research Site
Incheon, Korea, Republic of, 21565
Research Site
Jinju-si, Korea, Republic of, 660-702
Research Site
Seongnam-si, Korea, Republic of, 13620
Research Site
Seoul, Korea, Republic of, 03080
Research Site
Seoul, Korea, Republic of, 03181
Research Site
Seoul, Korea, Republic of, 156-707
Research Site
Ulsan, Korea, Republic of, 44033
Taiwan
Research Site
Kaohsiung, Taiwan
Research Site
Taichung, Taiwan, 40705
Research Site
Taipei, Taiwan, 10002
Sponsors and Collaborators
AstraZeneca
Investigators
Layout table for investigator information
Principal Investigator: Leora Horn, MD Vanderbilt University, Nashville, USA
Principal Investigator: James CH Yang, MD National Taiwan University Hospital, Taiwan
  Study Documents (Full-Text)

Documents provided by AstraZeneca:
Study Protocol  [PDF] March 2, 2017
Statistical Analysis Plan  [PDF] August 21, 2017


Additional Information:
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02454933     History of Changes
Other Study ID Numbers: D5165C00001
First Posted: May 27, 2015    Key Record Dates
Results First Posted: August 10, 2018
Last Update Posted: June 11, 2019
Last Verified: June 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
Phase III Open Label Study; AZD9291 plus MEDI4736 versus AZD9291 Monotherapy; NSCLC After Previous EGFR TKI Therapy; T790M Mutation Positive Tumours.

Additional relevant MeSH terms:
Layout table for MeSH terms
Durvalumab
Osimertinib
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action