Patients with extensive-stage small-cell lung cancer (ED-SCLC) who have refractory or resistant disease from prior platinum-based chemotherapy. MedDRA version: 21.1 Level: PT Classification code 10041068 Term: Small cell lung cancer extensive stage System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: durvalumab
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: durvalumab
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Conce
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria (applicable to all arms) - Adults with ED SCLC who have have demonstrated progressive disease either during first-line platinum-based chemotherapy (platinum refractory) or within 90 days of completing platinum basedchemotherapy (platinum resistant) and have not received further treatment. - Brain metastases must be asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatment. - At least 1 lesion, not previously irradiated, that can be accurately measured at baseline. - Life expectancy of at least 8 weeks. - Adequate organ and marrow function - WHO/ECOG PS of 0-1 at enrollment Inclusion criteria (Arm A specific) - Body weight >30 kg. - No prior exposure to immune mediated therapy, excluding therapeutic anticancer vaccines. Inclusion criteria (Arm B specific) - Able and willing to swallow oral medication Inclusion Criteria (Arm C specific) -Able and willing to swallow oral medication Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: Exclusion criteria (applicable to all arms) - Participation in another clinical study, major surgery, radiation therapy within 28 days. - Any condition that, in the opinion of the Investigator, would interfere with the evaluation of the IP or interpretation of patient safety or study results. - History of ILD, another primary malignancy, leptomeningeal carcinomatosis or spinal cord compression Exclusion criteria (Arm A specific) - Any concurrent cancer treatment. - Live vaccines within 30 days. - Known hypersensitivity to IP or excipient. - Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study. - Active autoimmune disease, including a paraneoplastic syndrome of autoimmune nature. - Active or prior documented autoimmune or inflammatory disorders. - Any unresolved toxicity (CTCAE Grade >2) from previous anticancer therapy. - History of allogenic organ transplantation or active primary immunodeficiency. - Active infection. - Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. Exclusion criteria (Arm B specific) - Prior exposure to any WEE1 inhibitors. - Products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4. Coadministration of rosuvastatin, aprepitant or fosaprepitant or any herbal preparations.. Grapefruit and Seville oranges should be avoided while taking AZD1775. - Any known hypersensitivity or contraindication to IP or CBDP. - QTcF > 470 msec or congenital long QT syndrome. - Any current or within 6 months cardiac diseases NYHA = Class 2: unstable angina pectoris, congestive heart failure, acute MI, conduction abnormality not controlled with pacemaker or medication, significant ventricular or supraventricular arrhythmias. - A recent history of Torsades de pointes Exclusion criteria (Arm C specific) - Cytotoxic chemotherapy within 21 days of Cycle 1 Day 1 is not permitted - Previous treatment with a PARP inhibitor (including olaparib) or ATR inhibitor - Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors - Concomitant use of known strong or moderate CYP3A inducers - Persisting (> 4 weeks) severe pancytopenia due to previous therapy - Cardiac dysfunction - Refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection - Patients with uncontrolled seizures - Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks before the dosing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the preliminary efficacy of each treatment arm in terms of Overall Response Rate. ORR will be evaluated using Investigator assessments according to RECIST 1.1;Secondary Objective: 1. To further assess the preliminary efficacy of each treatment arm in terms of DoR, DCR, TTR, PFS, and overall survival (OS) 2. To assess the pharmacokinetics (PK) of novel combination treatments ;Primary end point(s): Overall Response rate evaluated by using Investigator assessments according to RECIST 1.1;Timepoint(s) of evaluation of this end point: The primary analysis of ORR will occur approximately 12 weeks after the last patient has initiated treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To further assess the preliminary efficacy of each treatment arm in terms of DoR, DCR, TTR, PFS, and overall survival (OS);Timepoint(s) of evaluation of this end point: The primary analysis of ORR will occur approx. 12 weeks after the last patient has initiated treatment. This is planned to ensure the data cut off for ORR analysis follows the 12 week RECIST assessment for the last subject to be treated. However, in the situation where this scan does not occur due to this subject having experienced another progression event (e.g. death) the primary analysis DCO will be when all subjects have been followed for at least 12 weeks or until death if this is earlier. All study endpoints will be analyzed at this time includingincluding OS. The Sponsor will determine at that time whether any further follow up for OS would be required. | — |
Countries
Germany, Hungary, Poland, Spain, Ukraine
Contacts
Public ContactInformation Center
AstraZeneca AB
Outcome results
None listed