- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02937818
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, Open-Label, Multi-Arm Study to Determine the Preliminary Efficacy of Novel Combinations of Treatment in Patients With Platinum Refractory Extensive-Stage Small-Cell Lung Cancer
Study Overview
Status
Intervention / Treatment
Detailed Description
This study is modular in design, allowing evaluation of the preliminary efficacy, safety, tolerability, and immunogenicity of novel combinations of immunotherapies and/or deoxyribonucleic acid (DNA) damage repair inhibitors in patients with platinum refractory or resistant extensive-stage-disease SCLC. Patients who have progressive disease (PD) during first-line platinum-based chemotherapy (platinum refractory) or PD within 90 days after completing first-line platinum-based chemotherapy (platinum resistant) will be enrolled to the study. The primary objective of the study is to assess the preliminary efficacy of each treatment arm based on objective response rate (ORR).
This study consists of a number of arms (sub-studies), each evaluating the efficacy, safety, and tolerability of a specific agent or combination. This study was initially open with 2 arms (Arms A and B), and additional arms may open, provided there is compelling rationale for the combination and safe and tolerable doses and schedules have been determined from ongoing Phase I studies. There are 2 pre-defined arms:
A. Durvalumab + tremelimumab followed by durvalumab monotherapy B. AZD1775 + carboplatin (CBDP)
Further arm was added in amendment 3:
C. AZD6738 + olaparib Amendment #4 was updated with possibility to allow expansion of any arm, to a total of 40 eligible subjects, based on Review Committee assessment of data from the first 20 subjects (from Stage 1 and Stage 2). Currently Arm A will enroll 20 additional patients into expansion.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Gauting, Germany, 82131
- Research Site
-
-
-
-
-
Kecskemét, Hungary, 6000
- Research Site
-
Miskolc, Hungary, 3529
- Research Site
-
Székesfehérvár, Hungary, 8000
- Research Site
-
Törökbálint, Hungary, 2045
- Research Site
-
-
-
-
-
Poznań, Poland, 60-569
- Research Site
-
Warszawa, Poland, 02-781
- Research Site
-
-
-
-
-
Sevilla, Spain, 41009
- Research Site
-
Valencia, Spain, 46009
- Research Site
-
-
-
-
-
Dnipro, Ukraine, 49102
- Research Site
-
Ivano-Frankivsk, Ukraine, 76018
- Research Site
-
Sumy, Ukraine, 40022
- Research Site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ARM A
|
Durvalumab + tremelimumab via intravenous (IV) infusion every 4 weeks (q4w), starting on Week 0, for up to a total of 4 months (4 cycles) followed by durvalumab monotherapy via IV infusion q4w, starting on Week 16 until PD, or for other discontinuation criteria.
|
Experimental: ARM B
|
AZD1775 twice daily (oral) for 2.5 days from Day 1 + CBDP area under the curve 5 (Day1) (IV); every 3 weeks.
|
Experimental: ARM C
|
AZD6738 once a day (oral) for 7 days from Day 1 + olaparib twice a day(oral) for 28 days from Day 1, every 4 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Overall Response
Time Frame: Until disease progression [PD] (Up to 3.5 Years)
|
Overall Response Rate (ORR) using Investigator assessments according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
ORR was defined as the number (percentage) of participants with a confirmed Complete Response (CR) or confirmed Partial Response (PR) and was estimated for each treatment arm with corresponding 2-sided 95% exact confidence intervals (CIs).
A confirmed response of CR/PR meant that a response of CR/PR was recorded at one visit and confirmed by repeat imaging, preferably at the next regularly scheduled imaging visit, and not less than 4 weeks after the visit when the response was first observed, with no evidence of progression between the initial and CR/PR confirmation visit.
|
Until disease progression [PD] (Up to 3.5 Years)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Duration of Response (DoR)
Time Frame: Until disease progression or data cut-off or Death (Up to 3.5 Years)
|
The DoR was defined as the time from the date of first documented response (which was subsequently confirmed) CR/PR until the date of documented progression, or death in the absence of disease progression.
The DoR in participants with confirmed objective response are reported.
|
Until disease progression or data cut-off or Death (Up to 3.5 Years)
|
Percentage of Participants With Disease Control at 12 Weeks
Time Frame: At 12 Weeks
|
The disease control rate (DCR) at 12 weeks was defined as the percentage of participants who had a best objective response of CR or PR in the first 13 weeks or who had demonstrated stable disease (SD) for a minimum interval of 11 weeks following the start of study treatment.
The DCR was determined programmatically based on RECIST 1.1 using site Investigator data and all data up until the first progression event.
|
At 12 Weeks
|
Time to Response (TTR)
Time Frame: Until disease progression or data cut-off or Death (Up to 3.5 Years)
|
The TTR (per RECIST 1.1 as assessed by the Investigator) was defined as the time from the date of first dose until the first date of documented response.
|
Until disease progression or data cut-off or Death (Up to 3.5 Years)
|
Progression Free Survival (PFS)
Time Frame: Until disease progression or data cut-off or Death (Up to 3.5 Years)
|
The PFS (per RECIST 1.1 according to the Investigator's assessment) was defined as the time from the date of the first dose of study treatment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from allocated therapy or received another anti-cancer therapy prior to progression.
|
Until disease progression or data cut-off or Death (Up to 3.5 Years)
|
Overall Survival (OS)
Time Frame: Until disease progression or data cut-off or Death (Up to 3.5 Years)
|
The OS was defined as the time from the date of the first dose of study treatment until death due to any cause.
|
Until disease progression or data cut-off or Death (Up to 3.5 Years)
|
Time to Maximum Concentration (Tmax)
Time Frame: Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose)
|
Time to maximum concentration for ceralasertib and olaparib are reported.
|
Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose)
|
Maximum Concentration (Cmax)
Time Frame: Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose)
|
Maximum concentration for ceralasertib and olaparib are reported.
|
Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose)
|
Partial Area Under the Concentration-time Curve (AUC0-6)
Time Frame: Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) and Cycle 1 Day 7 (pre-dose and post-dose)
|
Partial area under the concentration-time curve for ceralasertib and olaparib are reported.
|
Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) and Cycle 1 Day 7 (pre-dose and post-dose)
|
Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t)
Time Frame: Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) and Cycle 1 Day 7 (pre-dose and post-dose)
|
Area under the concentration-time curve from time zero to the last measurable concentration for Ceralasertib and Olaparib are reported.
|
Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) and Cycle 1 Day 7 (pre-dose and post-dose)
|
Time to Maximum Concentration at Steady State (Tmax,ss)
Time Frame: Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose)
|
Time to maximum concentration at steady state for Ceralasertib and Olaparib are reported.
|
Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose)
|
Maximum Concentration at Steady State (Cmax,ss)
Time Frame: Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose)
|
Maximum concentration at steady state for Ceralasertib and Olaparib are reported.
|
Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose)
|
Minimum Concentration at Steady State (Cmin,ss)
Time Frame: Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose)
|
Minimum concentration at steady state for Ceralasertib and Olaparib are reported.
|
Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose)
|
Area Under the Concentration-time Curve at Steady State (AUCss)
Time Frame: Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose)
|
Area under the concentration-time curve at steady state at steady state for Ceralasertib and Olaparib are reported.
|
Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose)
|
Apparent Clearance of Drug at Steady State at Steady State (CLss/F)
Time Frame: Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose)
|
Area under the concentration-time curve at steady state at steady state for Ceralasertib and Olaparib are reported.
|
Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose)
|
Serum Concentrations of Durvalumab and Tremelimumab
Time Frame: Durvalumab: Cycle 1 (each cycle was 4 weeks) Day 1(post-dose); Cycle 2 Day 1(pre-dose); Cycle 5 Day 1 (pre-dose); Tremelimumab: Cycle 1 (each cycle was 4 weeks) Day 1 (post-dose); Cycle 2 Day 1 (pre-dose); Cycle 5 Day 1 (No dose); Cycle 7 Day 1 (No dose)
|
Serum concentrations of Durvalumab and Tremelimumab are reported.
|
Durvalumab: Cycle 1 (each cycle was 4 weeks) Day 1(post-dose); Cycle 2 Day 1(pre-dose); Cycle 5 Day 1 (pre-dose); Tremelimumab: Cycle 1 (each cycle was 4 weeks) Day 1 (post-dose); Cycle 2 Day 1 (pre-dose); Cycle 5 Day 1 (No dose); Cycle 7 Day 1 (No dose)
|
Plasma Concentrations of Adavosertib and Carboplatin
Time Frame: Adavosertib: Cycle 1 (each cycle was 21 days) Day 3 (pre-dose and post-dose); Cycle 3 Day 3 (pre-dose and post-dose); Carboplatin: Cycle 1 (each cycle was 21 days) Day 1 (post-dose)
|
Plasma concentrations of Adavosertib and Carboplatin are reported.
|
Adavosertib: Cycle 1 (each cycle was 21 days) Day 3 (pre-dose and post-dose); Cycle 3 Day 3 (pre-dose and post-dose); Carboplatin: Cycle 1 (each cycle was 21 days) Day 1 (post-dose)
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Day 1 until disease progression, and follow-up visit (Up to 3.5 Years)
|
An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
SAE is an AE that results in any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, or is a significant medical event.
|
Day 1 until disease progression, and follow-up visit (Up to 3.5 Years)
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Haiyi Jiang, M.D., AstraZeneca
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- Platinum Refractory Extensive-Stage Carcinoma, Small Cell Lung
- Platinum Refractory Extensive-Stage Oat Cell Carcinoma of Lung
- Platinum Refractory Extensive-Stage Oat Cell Lung Cancer
- Platinum Refractory Extensive-Stage Small Cell Cancer Of The Lung
- Platinum Refractory Extensive-Stage Small Cell Lung Cancer
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma
- Small Cell Lung Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Poly(ADP-ribose) Polymerase Inhibitors
- Carboplatin
- Olaparib
- Durvalumab
- Tremelimumab
- Adavosertib
Other Study ID Numbers
- D419QC00002
- 2016-001202-42 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Platinum Refractory Extensive-Stage Small Cell Lung Carcinoma
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingPlatinum-Resistant Lung Small Cell Carcinoma | Platinum-Sensitive Lung Small Cell Carcinoma | Recurrent Extensive Stage Lung Small Cell Carcinoma | Refractory Extensive Stage Lung Small Cell CarcinomaUnited States
-
National Cancer Institute (NCI)RecruitingExtensive Stage Lung Small Cell Carcinoma | Limited Stage Lung Small Cell Carcinoma | Platinum-Resistant Lung Small Cell Carcinoma | Platinum-Sensitive Lung Small Cell Carcinoma | Recurrent Lung Small Cell CarcinomaUnited States
-
Jonsson Comprehensive Cancer CenterPfizer; Translational Research in OncologyRecruitingRecurrent Extensive Stage Small Cell Lung Carcinoma | Refractory Extensive Stage Small Cell Lung CarcinomaUnited States
-
National Cancer Institute (NCI)Active, not recruitingExtensive Stage Lung Small Cell Carcinoma | Limited Stage Lung Small Cell Carcinoma | Platinum-Resistant Lung Small Cell Carcinoma | Platinum-Sensitive Lung Small Cell Carcinoma | Bladder Small Cell Neuroendocrine Carcinoma | Extrapulmonary Small Cell Neuroendocrine Carcinoma | Recurrent Lung... and other conditionsUnited States
-
Institut BergoniéAstraZeneca; PharmaMarRecruitingSmall Cell Lung Cancer | Platinum-Sensitive Lung Small Cell Carcinoma | Extensive-stage Small-cell Lung CancerFrance
-
SWOG Cancer Research NetworkNational Cancer Institute (NCI)RecruitingExtensive Stage Lung Small Cell Carcinoma | Limited Stage Lung Small Cell Carcinoma | Lung Small Cell CarcinomaUnited States, Canada, Korea, Republic of, Mexico
-
University of WashingtonNational Cancer Institute (NCI); Imago BioSciences, Inc., a subsidiary of Merck...RecruitingExtensive Stage Lung Small Cell Carcinoma | Limited Stage Lung Small Cell CarcinomaUnited States
-
Vanderbilt-Ingram Cancer CenterGenentech, Inc.RecruitingStage IV Lung Cancer | Extensive Stage Lung Small Cell CarcinomaUnited States
-
Ohio State University Comprehensive Cancer CenterNational Institute on Aging (NIA)RecruitingStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage IV Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Extensive Stage Lung Small Cell Carcinoma | Unresectable Lung Non-Small Cell Carcinoma | Advanced Lung Non-Small Cell Carcinoma | Advanced... and other conditionsUnited States
-
University of WashingtonAstraZenecaWithdrawnStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage IV Lung Cancer AJCC v8 | Extensive Stage Lung Small Cell CarcinomaUnited States
Clinical Trials on Durvalumab and Tremelimumab
-
Canadian Cancer Trials GroupAstraZenecaActive, not recruiting
-
University of Erlangen-Nürnberg Medical SchoolActive, not recruitingLocally Advanced Head and Neck Squamous Cell CarcinomaGermany
-
John L. Villano, MD, PhDActive, not recruitingTumor, SolidUnited States
-
Centre Georges Francois LeclercAstraZenecaCompletedColorectal Cancer MetastaticFrance
-
Seoul National University HospitalUnknownDurvalumab + Tremelimumab Combination Treatment, Pulmonary Sarcomatoid Carcinoma, NSCLCKorea, Republic of
-
Yonsei UniversityCompletedMetastatic Breast CancerKorea, Republic of
-
Samsung Medical CenterActive, not recruitingHead and Neck Squamous Cell CarcinomaKorea, Republic of
-
Memorial Sloan Kettering Cancer CenterAstraZenecaCompletedAdenocarcinoma of the Bladder | Squamous Cell Carcinoma of the Bladder | Metastatic Bladder Cancer | Non-Transitional Cell Carcinoma of the Urothelial Tract | Small Cell of the BladderUnited States
-
Italian Network for Tumor Biotherapy FoundationAstraZenecaUnknownPeritoneal Mesothelioma | Pleural MesotheliomaItaly
-
Assistance Publique - Hôpitaux de ParisAstraZenecaNot yet recruitingBCLC A Hepatocellular Carcinoma Non-resectable and Not Amenable for RFAFrance