Clinical Trials /

A Study of Olaparib and Low Dose Radiotherapy for Small Cell Lung Cancer

NCT03532880

Description:

The purpose of this study is to test the safety of a new medication, Olaparib, combined with radiation therapy for participants with small cell lung cancer.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Olaparib and Low Dose Radiotherapy for Small Cell Lung Cancer
  • Official Title: A Phase I Study of Olaparib and Low Dose Thoracic Radiotherapy for Extensive Stage Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 18-195
  • NCT ID: NCT03532880

Conditions

  • Small-cell Lung Cancer
  • Small Cell Lung Carcinoma

Interventions

DrugSynonymsArms
Olaparib Pill 50 mgParticipants with Small Cell Lung Cancer
Olaparib Pill 100 mgParticipants with Small Cell Lung Cancer
Olaparib Pill 150 mgParticipants with Small Cell Lung Cancer
Olaparib Pill 200 mgParticipants with Small Cell Lung Cancer
Olaparib Pill 250 mgParticipants with Small Cell Lung Cancer
Olaparib Pill 300 mgParticipants with Small Cell Lung Cancer

Purpose

The purpose of this study is to test the safety of a new medication, Olaparib, combined with radiation therapy for participants with small cell lung cancer.

Trial Arms

NameTypeDescriptionInterventions
Participants with Small Cell Lung CancerExperimental
  • Olaparib Pill 50 mg
  • Olaparib Pill 100 mg
  • Olaparib Pill 150 mg
  • Olaparib Pill 200 mg
  • Olaparib Pill 250 mg
  • Olaparib Pill 300 mg

Eligibility Criteria

        Inclusion Criteria:

          -  Histological documented diagnosis of SCLC confirmed by a MSKCC pathologist.

          -  Documented extensive disease, defined as any tumor beyond the above limited disease
             definition, including ipsilateral lung metastases and malignant pleural effusion

          -  Completion of induction chemotherapy with a minimum of 4 and no more than 6 cycles of
             a platinum agent and etoposide within 8 weeks of trial initiation.

          -  No disease progression (i.e.SD or better response by RECIST 1.1) at the completion of
             chemotherapy.

          -  Age 18 years or older.

          -  Intrathoracic disease should be encompassable in acceptable radiation fields per
             investigator clinical judgement.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnosfsky
             Performance Score (KPS) >/= 70

          -  Patients must have adequately recovered from any adverse events associated with prior
             immune-chemotherapy

          -  Adequate organ and marrow function, including:

               1. Haemoglobin >/= 8.0 g/dL with no blood transfusion in the past 28 days.

               2. Absolute neutrophil count (ANC) >/= 1.5 x 10^9/L.

               3. Platelet count >/= 100 x 10^9/L.

               4. Total bilirubin </= 1.5 x institutional upper limit of normal (ULN)

               5. Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT))
                  / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT))
                  </= 2.5 x institutional upper limit of normal unless liver metastases are present
                  in which case they must be </= 5x ULN.

               6. Patients must have creatinine clearance estimated using the Cockcroft-Gault
                  equation of >/= 51 mL/min

          -  Patients must have a life expectancy >/= 16 weeks.

          -  Postmenopausal or evidence of non-childbearing status for women of childbearing
             potential: negative serum pregnancy test within 28 days of study treatment and
             confirmed prior to treatment on day 1.

             a. Postmenopausal is defined as any one or more of the following: i. Age >/= 60 years.
             ii. Age < 60 and amenorrheic for 1 year or more in the absence of chemotherapy and/or
             hormonal treatment.

        iii. Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post
        menopausal range for women under 60.

        iv. Radiation-induced oophorectomy with last menses >1 year ago v. Chemotherapy-induced
        menopause with > 1 year interval since last menses. vi. Surgical sterilisation (bilateral
        oophorectomy or hysterectomy).

          -  Men and women of childbearing potential must be willing to us two highly effective
             forms of contraception while on treatment and for at least 3 months after last dose of
             study drug.

          -  Patient is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations.

          -  Written informed consent

        Exclusion Criteria:

          -  Untreated brain metastases.

          -  Pneumonitis

          -  Previous radiotherapy to thorax (prior breast RT is permitted).

          -  Patient is not a candidate for or declines consolidative thoracic radiotherapy.

          -  Patients receiving any systemic chemotherapy or thoracic radiotherapy within 3 weeks
             prior to study treatment.

          -  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.

          -  Exposure to an investigational product within 30 days or 5 half lives (whichever is
             longer) prior to start of the current study drug.

          -  Any previous treatment with PARP inhibitor, including olaparib, for the treatment of
             small cell lung cancer

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

          -  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 olaparib is 2 weeks.

          -  Concomitant use of known strong CYP3A inducers (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 olaparib is 5 weeks for enzalutamide or phenobarbital
             and 3 weeks for other agents.

          -  For patients who have received prior immunotherapy, treatment must be held from 10
             days prior to protocol treatment until 10 days after completing protocol treatment.

          -  Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2)
             caused by previous cancer therapy, excluding alopecia.

          -  Patients with myelodysplastic syndrome/acute leukaemia or with features suggestive
             thereof.

          -  Major surgery within 2 weeks of study treatment initiation and patients must have
             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. Examples
             include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3
             months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal
             cord compression, superior vena cava syndrome, extensive interstitial bilateral lung
             disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder
             that prohibits obtaining informed consent.

          -  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, e.g., patients who are known to be serologically positive
             for human immunodeficiency virus (HIV).

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

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

          -  Previous allogenic bone marrow transplant or double umbilical cord blood
             transplantation (dUCBT).

          -  Whole blood transfusions in the last 120 days prior to entry to the study (packed red
             blood cells and platelet transfusions are acceptable, for timing refer to inclusion
             criteria number 8)

          -  Other malignancy within the last 5 years except: adequately treated non-melanomatous
             skin cancer, curatively treated in situ cervical cancer, ductal carcinoma in situ
             (DCIS), FIGO Grade 1 endometrial carcinoma, or other solid tumours including lymphomas
             (without bone marrow involvement) curatively treated with no evidence of disease for
             >/= 5 years. Patients with a history of localised triple negative breast cancer may be
             eligible, provided they completed their adjuvant chemotherapy more than three years
             prior to registration, and that the patient remains free of recurrent or metastatic
             disease

          -  Absence of brain metastases is not required. Patients must not have symptomatic brain
             metastatic disease. The patient may be symptomatically controlled on a stable dose of
             corticosteroids before and during the study as long as these were started at least 4
             weeks prior to treatment.

          -  Patients with spinal cord compression unless considered to have received definitive
             treatment for this and evidence of clinically stable disease for 28 days.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) of olaparib in combination with low dose thoracic radiotherapy
Time Frame:1 year
Safety Issue:
Description:For safety, all adverse events as determined by the investigator using CTCAE

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Olaparib
  • Radiation therapy
  • 18-195
  • Memorial Sloan Kettering Cancer Center

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