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A Phase II, Study to Determine the Preliminary Efficacy of Novel Combinations of Treatment in Patients With Platinum Refractory Extensive-Stage Small-Cell Lung Cancer
A Phase II, Study to Determine the Preliminary Efficacy of Novel Combinations of Treatment in Patients With Platinum Refractory Extensive-Stage Small-Cell Lung Cancer
CompletedPhase 2
Sponsor: AstraZeneca
Conditions: Platinum Refractory Extensive-Stage Small Cell Lung Carcinoma
Interventions: Durvalumab and Tremelimumab, AZD1775 and carboplatin (CBPT), AZD6738 and olaparib
Countries: Germany, Hungary, Poland, Spain, Ukraine
Study design This is a Phase II, open-label, multi-drug, multi-center, multi-arm, signal-searching study in patients with extensive-stage small-cell lung cancer (SCLC) who have refractory or resistant disease from prior platinum-based chemotherapy.
Eligibility overview
Sex: ALL
Age: 18 Years to 130 Years
Healthy volunteers: No
Study type: INTERVENTIONAL
Eligibility criteria
Inclusion criteria (applicable to all arms) * Adults with histologically or cytologically documented ED SCLC who have demonstrated progressive disease either during first-line platinum-based chemotherapy (platinum refractory) or within 90 days of completing platinum based-chemotherapy (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 (per RECIST v 1.1 guidelines) * Life expectancy of at least 8 weeks. * 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. 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. * Uncontrolled intercurrent illness, including but not limited to interstitial lung disease. * History of another primary malignancy, leptomeningeal carcinomatosis or spinal cord compression. Exclusion criteria (Arm A specific) * Active autoimmune disease, including a paraneoplastic syndrome. * Active or prior documented autoimmune or inflammatory disorders. * Any unresolved toxicity (CTCAE Grade \>2) from previous anticancer therapy. * Active infection including tuberculosis, HIV, Hepatitis B or C. 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. Co-administration of rosuvastatin, atorvastatin, simvastatin and lovastatin, 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 and moderate CYP3A inhibitors * Concomitant use of known strong and moderate CYP3A inducers * Persisting (\> 4 weeks) severe pancytopenia due to previous therapy * Cardiac dysfunction * Refractory nausea and vomitting, chronic gastrointenstinal diseases or previous significant bowel resection * Patients with uncontrolled seizures * Intenstinal obstruction or CTCAE grade 3 or grade 4 GI bleeding within 4 weeks before dosing
Locations (12)
- Gauting, Germany
- Kecskemét, Hungary
- Miskolc, Hungary
- Székesfehérvár, Hungary
- Törökbálint, Hungary
- Poznan, Poland
- Warsaw, Poland
- Seville, Spain
- Valencia, Spain
- Dnipro, Ukraine
- Ivano-Frankivsk, Ukraine
- Sumy, Ukraine