Olaparib and Bevacizumab in Relapsed Small Cell Lung Cancer Subjects

NCT04939662 | Completed Phase 2

• 1 other identifier: SUKSES-B2
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single arm, multi-centre phase II study of olaparib and bevacizumab combination therapy in subjects with relapsed small cell lung cancer (SCLC) as a second or third line (systemic) therapy. Subjects will receive olaparib and bevacizumab combination therapy. The arm is composed of 28 subjects. Olaparib 300 mg bid per os every 12 hours administered each cycle day and bevacizumab 15 mg/kg via IV administered on Day 1 of every cycle for every 3 weeks. One cycle consists of 21 days.

Conditions

Lung Cancer

Keywords

SCLC; olaparib; bevacizumab; relapsed small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) by RECIST 1.1

  Response rate of chemotherapy in patients.

  through study completion, an average of 1 year

Secondary Outcomes (2)

• Overall survival (OS) and progression-free survival (PFS)

  through study completion, an average of 1 year

• Subgroup analyses based on biomarker

  through study completion, an average of 1 year

Study Arms (1)

Olaparib+Bevacizumab to SCLC patients

EXPERIMENTAL

Regimen and administration: Administration of olaparib Olaparib 300 mg bid per os every 12 hours D1-21 administered in each cycle days. One cycle consists of 21 days. Olaparib tablets should be taken at the same time each day, approximately 12 hours apart with one glass of water. Administration of bevacizumab Bevacizumab 15 mg/kg via IV administered on Day1 of each cycle. One cycle is consisted of 21 days. The subject's body weight criterion is based on C1D1 (first dose date), and if more than 10% of BW is increased and decreased, the drug dose is changed to that BW.

Drug: Olaparib+Bevacizumab to SCLC patients

Interventions

Olaparib+Bevacizumab to SCLC patients DRUG

Olaparib 300 mg bid per os every 12 hours D1-21 administered in each cycle days. One cycle consists of 21 days. Bevacizumab 15 mg/kg via IV administered on Day1 of each cycle. One cycle is consisted of 21 days. The subject's body weight criterion is based on C1D1 (first dose date), and if more than 10% of BW is increased and decreased, the drug dose is changed to that BW.

Also known as: Drug Combination Intervention

Olaparib+Bevacizumab to SCLC patients

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures
• SCLC that satisfies one or more of the following conditions; Histologically confirmed SCLC with documented
• \) ATM deficiency, SLFN11 positive, POU2F3 positive by immunohistochemistry 2) HR(homologous recombination) pathway gene mutation: BRCA 1/2, MRE11A, 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 with or without iCPI.
• Refractory to first-line chemotherapy or relapse within 6 months since the last dose of first-line chemotherapy
• If the subject corresponds to sensitive relapse (relapse more than 6 months since the last dose of first-line chemotherapy), she / he should receive second-line treatment before entering the study 4. Subjects (male/female) must be \> 18 years of age. 5. Subjects must have normal organ and bone marrow function measured within 14 days prior to administration of study treatment as defined below (transfusion allowed);
• Haemoglobin ≥ 10.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• No features suggestive of MDS/AML on peripheral blood smear
• White blood cells (WBC) \> 3x109/L
• Platelet count ≥ 100 x 109/L
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN
• Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 51 mL/min (Cockcroft-gault method).

You may not qualify if:

• Involvement in the planning and / or conduct of the study (applies to both AstraZeneca/Roche staff and / or staff at the study sites)
• Previous enrolment in the any of SUKSES umbrella trials.
• 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 not limited to olaparib.
• More than two prior chemotherapy regimens 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.
• Subjects with second primary cancer stable without treatment for 2 years are eligible for the trials. Adequately treated non-melanoma skin cancer, superficial urothelial tumor, early gastric cancer, in-situ cancer of the cervix, thyroid cancer or other solid tumours curatively treated with currently no evidence of disease is eligible for the trial.
• Subjects 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 subject 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.
• Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting \<\<select olaparib or study treatment\>\> is 2 weeks
• Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting \<\<select olaparib or study treatment\>\> is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
• 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.
• Subjects with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The subject can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. The subjects with brain metastases who is previously treated and currently in stable status, no clinical symptom or image confirmed disease progression, are eligible for the trial. The subjects with untreated asymptomatic brain metastases is also allowed for the trial.
• Major surgery within 14 days of starting study treatment or subjects not being recovered from any effects of any major surgery
• Subjects considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled major seizure discorder, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord compression which cause neurologic symptom (untreated and unstable for at least 28 days prior to study entry), superior vena cava syndrome, extensive bilateral lung disease on HRCT scan which cause respiratory distress or any psychiatric disorder that prohibits obtaining informed consent.

Sponsors & Collaborators

• Se-Hoon Lee: lead
• AstraZeneca: collaborator
• Roche Pharma AG: collaborator

Study Sites (1)

Samsung Medical Center

Seoul, Gangnam-gu, South Korea

Location

MeSH Terms

Conditions

Lung Neoplasms; Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Se-Hoon Lee, Professor

  Samsung Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Samsung Medical Center

Model Details: Interventional Arm

Study Record Dates

• First Submitted: June 2, 2021
• First Posted: June 25, 2021
• Study Start: June 11, 2021
• Primary Completion: October 27, 2023
• Study Completion: October 27, 2023
• Last Updated: January 2, 2024

Record last verified: 2023-12

Locations

KR (1)