Phase II, single-arm study of olaparib and bevacizumab combination therapy in relapsed small cell lung cancer subjects
- Conditions
- Neoplasms
- Registration Number
- KCT0006306
- Lead Sponsor
- Samsung Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 28
Subjects must fulfill all of the following inclusion criteria.
1.Provision of informed consent prior to any study specific procedures
2.SCLC that satisfies one or more of the following conditions;
Histologically confirmed SCLC with documented
1)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.
3.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 = 20 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).
A.CrCl = (140-age) x (weight (kg)) x (0.85 for female)
i.----------------------------------------------------------
A.(72 x serum creatinine (mg/dL))
6.ECOG performance status 0-2 subject must have a life expectancy = 16 weeks.
7.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. Postmenopausal is defined as:
-Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments,
-LH and FSH levels in the post-menopausal range for women under 50,
-radiation-induced oophorectomy with last menses > 1 year ago,
-chemotherapy-induced menopause with > 1-year interval since last menses,
-or surgical sterilization (bilateral oophorectomy or hysterectomy).
8. The subject 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.
9. At least one lesion, not previously irradiated, that can be accurately measured at baseline as = 10 mm in the longest diameter (except lymph nodes which must have short axis = 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
10. Provision of informed consent for genetic research.
11. Male patients must use a condom during treatment and for 6 months after the last dose when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients and female patients should also use a highly effective form of contraception ([see appendix A for acceptable method
Subjects meeting any of the following exclusion criteria will be excluded from study.
1.Involvement in the planning and / or conduct of the study (applies to both AstraZeneca/Roche staff and / or staff at the study sites)
2.Previous enrolment in the any of SUKSES umbrella trials.
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 not limited to olaparib.
5.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.
6.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.
7.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.
8.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 <> 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 <> is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
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.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.
12.Major surgery within 14 days of starting study treatment or subjects not being recovered from any effects of any major surgery
13.Subjects considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. E
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) by RECIST 1.1
- Secondary Outcome Measures
Name Time Method Overall survival (OS) and progression-free survival (PFS)