SUKSES-B: 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

Sponsor

Samsung Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT03009682

Collaborator

(none)

Enrollment

Location

Arm

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Cancer	Drug: Olaparib	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Aug 1, 2016

Actual Primary Completion Date :

Jan 1, 2021

Actual Study Completion Date :

Jan 1, 2021

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) by RECIST 1.1 [Up to 30 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Provision of informed consent prior to any study specific procedures
Small cell lung cancer that satisfies one or more of the following conditions:

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.

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.

Patients (male/female) must be > 20 years of age.
Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
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,
Provision of informed consent for genetic research.

Exclusion Criteria:

Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
Previous enrolment in the present study
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).
Any previous treatment with a PARP inhibitor, including olaparib.
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.
Patients with second primary cancer
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.
Concomitant use of known CYP3A4 inhibitors such as ketokonazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir
Persistent toxicities (>=CTCAE grade 2) with the exception of alopecia, caused by previous cancer therapy.
Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
Patients with myelodysplastic syndrome/acute myeloid leukaemia
Patients with symptomatic uncontrolled brain metastases.
Major surgery within 14 days of starting study treatment or patients not being recovered from any effects of any major surgery
Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
Breast feeding women
Immunocompromised patients,
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.
Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
Patients with uncontrolled seizures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Samsung Medical Center	Seoul		Korea, Republic of	135-710

Sponsors and Collaborators

Samsung Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Keunchil Park, professor, MD, Samsung Medical Center

ClinicalTrials.gov Identifier:

NCT03009682

Other Study ID Numbers:

2016-03-078

First Posted:

Jan 4, 2017

Last Update Posted:

Feb 18, 2021

Last Verified:

Feb 1, 2021

Additional relevant MeSH terms:

Lung Neoplasms

Small Cell Lung Carcinoma

Olaparib

Study Results

No Results Posted as of Feb 18, 2021