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)

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)

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.

Study Overview

• Status: Completed
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: Olaparib

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Olaparib 300 mg; Olaparib 300 mg BID per os every 12 hours administered daily. One cycle is consisted of 21 days

Drug: Olaparib; Dosage and Schedule : Olaparib 300 mg BID per os every 12 hours administered daily. One cycle is consisted of 21 days. Two x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water. The olaparib tablets should be swallowed whole and not chewed, crushed, dissolved or divided. Olaparib can be taken with a light meal/snack.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (ORR) by RECIST 1.1	Up to 30 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): January 1, 2021
• Study Completion (Actual): January 1, 2021

Study Registration Dates

• First Submitted: December 27, 2016
• First Submitted That Met QC Criteria: January 3, 2017
• First Posted (Estimate): January 4, 2017

Study Record Updates

• Last Update Posted (Actual): February 18, 2021
• Last Update Submitted That Met QC Criteria: February 16, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Olaparib
• Other Study ID Numbers: 2016-03-078