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

NCT02937818 | Completed Phase 2 Results

• 2 other identifiers: D419QC000022016-001202-42
• Study Type: interventional
• Target: 72
• Locations: 5 countries
• Sites: 12

Brief Summary

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.

Conditions

Platinum Refractory Extensive-Stage Small Cell Lung Carcinoma

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Overall Response

  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 Outcomes (17)

• Duration of Response (DoR)

  Until disease progression or data cut-off or Death (Up to 3.5 Years)

• Percentage of Participants With Disease Control at 12 Weeks

  At 12 Weeks

• Time to Response (TTR)

  Until disease progression or data cut-off or Death (Up to 3.5 Years)

• Progression Free Survival (PFS)

  Until disease progression or data cut-off or Death (Up to 3.5 Years)

• Overall Survival (OS)

  Until disease progression or data cut-off or Death (Up to 3.5 Years)

Study Arms (3)

ARM A

EXPERIMENTAL

Drug: Durvalumab and Tremelimumab

ARM B

EXPERIMENTAL

Drug: AZD1775 and carboplatin (CBPT)

ARM C

EXPERIMENTAL

Drug: AZD6738 and olaparib

Interventions

Durvalumab and Tremelimumab DRUG

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.

ARM A

AZD1775 and carboplatin (CBPT) DRUG

AZD1775 twice daily (oral) for 2.5 days from Day 1 + CBDP area under the curve 5 (Day1) (IV); every 3 weeks.

ARM B

AZD6738 and olaparib DRUG

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

ARM C

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Body weight \>30 kg.
• No prior exposure to immune mediated therapy, excluding therapeutic anticancer vaccines.
• Able and willing to swallow oral medication.

You may not qualify if:

• 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.
• 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.
• 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.
• Cytotoxic chemotherapy within 21 days of Cycle 1 Day 1 is not permitted

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (12)

Research Site

Gauting, 82131, Germany

Location

Research Site

Kecskemét, 6000, Hungary

Location

Research Site

Miskolc, 3529, Hungary

Location

Research Site

Székesfehérvár, 8000, Hungary

Location

Research Site

Törökbálint, 2045, Hungary

Location

Research Site

Poznan, 60-569, Poland

Location

Research Site

Warsaw, 02-781, Poland

Location

Research Site

Seville, 41009, Spain

Location

Research Site

Valencia, 46009, Spain

Location

Research Site

Dnipro, 49102, Ukraine

Location

Research Site

Ivano-Frankivsk, 76018, Ukraine

Location

Research Site

Sumy, 40022, Ukraine

Location

Related Links

• Related Info
• Related Info
• CSR Synopsis

MeSH Terms

Interventions

durvalumab; tremelimumab; adavosertib; Carboplatin; ceralasertib; olaparib

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Haiyi Jiang, M.D.

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2016
• First Posted: October 19, 2016
• Study Start: November 28, 2016
• Primary Completion: June 22, 2020
• Study Completion: November 27, 2023
• Last Updated: June 7, 2024
• Results First Posted: September 9, 2021

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

PL (2); UA (3); DE (1); HU (4); ES (2)