Clinical Trials /

Olaparib Monotherapy in Relapsed Small Cell Lung Cancer Patients With HR Pathway Gene Mutations Not Limited to BRCA 1/2 Mutations, ATM Deficiency or MRE11A Mutations

NCT03009682

Description:

This study is a single arm, multi-center phase II study of olaparib monotherapy in patients with relapsed small cell lung cancer (SCLC) harboring HR pathway gene mutations not limited to BRCA 1/2 mutations, ATM deficiency or MRE11A mutations as second or third line chemotherapy. Target subject population: Patients with small cell lung cancer that have progressed following first-line platinum-based therapy. Patients must have imaging confirmed progression on 1st line chemotherapy for SCLC treatment, which must have contained platinum-based regimen, with at least one measurable lesion per RECIST 1.1.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Olaparib Monotherapy in Relapsed Small Cell Lung Cancer Patients With HR Pathway Gene Mutations Not Limited to BRCA 1/2 Mutations, ATM Deficiency or MRE11A Mutations
  • Official Title: Phase II, Single-arm Study of Olaparib Monotherapy in Relapsed Small Cell Lung Cancer Patients With HR Pathway Gene Mutations Not Limited to BRCA 1/2 Mutations, ATM Deficiency or MRE11A Mutations(SUKSES-B)

Clinical Trial IDs

  • ORG STUDY ID: 2016-03-078
  • NCT ID: NCT03009682

Conditions

  • Small Cell Lung Cancer

Interventions

DrugSynonymsArms
OlaparibOlaparib 300 mg

Purpose

This study is a single arm, multi-center phase II study of olaparib monotherapy in patients with relapsed small cell lung cancer (SCLC) harboring HR pathway gene mutations not limited to BRCA 1/2 mutations, ATM deficiency or MRE11A mutations as second or third line chemotherapy. Target subject population: Patients with small cell lung cancer that have progressed following first-line platinum-based therapy. Patients must have imaging confirmed progression on 1st line chemotherapy for SCLC treatment, which must have contained platinum-based regimen, with at least one measurable lesion per RECIST 1.1.

Trial Arms

NameTypeDescriptionInterventions
Olaparib 300 mgOtherOlaparib 300 mg BID per os every 12 hours administered daily. One cycle is consisted of 21 days
  • Olaparib

Eligibility Criteria

        Inclusion Criteria:

          1. Provision of informed consent prior to any study specific procedures

          2. Small cell lung cancer that satisfies one or more of the following conditions:

        1) BRCA1 or BRCA2 mutation, ATM deficiency, MRE11A mutation 2) Mutation of other
        HR(homologous recombination) pathway genes: BLM, NBN, RAD50, RAD52, RAD54L, RAD51, RAD51B,
        RAD51C, RAD51D, RECQL, RECQL4, RECQL5, RPA1, WRN etc.

        3. Small cell lung cancer that has progressed during or after first-line therapy.

          -  The 1st line regimen must have contained platinum based regimen.

          -  Refractory to first-line chemotherapy or relapse within 6 months since the last dose
             of first-line chemotherapy

          -  If the patient correspond to sensitive relapse (relapse more than 6 months since the
             last dose of first-line chemotherapy), she/he should get second- line treatment.

             4. Patients (male/female) must be > 20 years of age.

             5. Patients must have normal organ and bone marrow function measured within 28 days
             prior to administration of study treatment as defined below:

             6. ECOG performance status 0-1 7. Patients must have a life expectancy ≥ 16 weeks 8.
             Evidence of non-childbearing status for women of childbearing potential: negative
             urine or serum pregnancy test within 28 days of study treatment, confirmed prior to
             treatment on day 1 9. Patient is willing and able to comply with the protocol for the
             duration of the study including undergoing treatment and scheduled visits and
             examinations including follow up. 10. At least one lesion, not previously irradiated,
             11. Provision of informed consent for genetic research.

        Exclusion Criteria:

          1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             staff and/or staff at the study site)

          2. Previous enrolment in the present study

          3. Participation in another clinical study with an investigational product during the
             last 2 weeks (or a longer period depending on the defined characteristics of the
             agents used).

          4. Any previous treatment with a PARP inhibitor, including olaparib.

          5. More than two prior chemotherapy regimen for the treatment of small cell lung cancer.
             Pazopanib maintenance or immune checkpoint inhibitor (CTLA4, PD-1 or PD-L1 monoclonal
             antibody) is not considered as line of treatment.

          6. Patients with second primary cancer

          7. Patients receiving any systemic chemotherapy, radiotherapy (except for palliative
             reasons), within 2 weeks from the last dose prior to study treatment (or a longer
             period depending on the defined characteristics of the agents used). The patient can
             receive a stable dose of bisphosphonates or denosumab for bone metastases, before and
             during the study as long as these were started at least 4 weeks prior to treatment
             with study drug.

          8. Concomitant use of known CYP3A4 inhibitors such as ketokonazole, itraconazole,
             ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir

          9. Persistent toxicities (>=CTCAE grade 2) with the exception of alopecia, caused by
             previous cancer therapy.

         10. Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or
             family history of long QT syndrome.

         11. Patients with myelodysplastic syndrome/acute myeloid leukaemia

         12. Patients with symptomatic uncontrolled brain metastases.

         13. Major surgery within 14 days of starting study treatment or patients not being
             recovered from any effects of any major surgery

         14. Patients considered a poor medical risk due to a serious, uncontrolled medical
             disorder, non-malignant systemic disease or active, uncontrolled infection.

         15. Patients unable to swallow orally administered medication and patients with
             gastrointestinal disorders likely to interfere with absorption of the study
             medication.

         16. Breast feeding women

         17. Immunocompromised patients,

         18. Patients with known active hepatic disease (i.e., Hepatitis B or C) due to risk of
             transmitting the infection through blood or other body fluids.

         19. Patients with a known hypersensitivity to olaparib or any of the excipients of the
             product.

         20. Patients with uncontrolled seizures.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR) by RECIST 1.1
Time Frame:Up to 30 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of response
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Disease control rate
Time Frame:at 12 weeks
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Number of participants with Adverse Events as Assessed by CTCAE v4.03
Time Frame:Up to 30 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Samsung Medical Center

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