Olaparib and Low Dose Radiation Therapy in Treating Participants with Extensive Stage Small Cell Lung Cancer

Status: Active

Description

This phase I trial studies the side effects and best dose of olaparib when giving together with radiation therapy in treating participants with small cell lung cancer that has spread from the original site of growth to other sites. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving olaparib and radiation therapy may work better in treating participants with extensive stage small cell lung cancer.

Eligibility Criteria

Inclusion Criteria

  • Histological documented diagnosis of small cell lung cancer (SCLC) confirmed by a Memorial Sloan Kettering Cancer Center (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. stable disease [SD] or better response by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) at the completion of chemotherapy.
  • Intrathoracic disease should be encompassable in acceptable radiation fields per investigator clinical judgement.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky performance score [KPS] >= 70).
  • Hemoglobin >= 8.0 g/dL with no blood transfusion in the past 28 days.
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L.
  • Platelet count >= 100 x 10^9/L.
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN).
  • 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.
  • 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. * Postmenopausal is defined as any one or more of the following: ** Age >= 60 years. ** Age < 60 and amenorrheic for 1 year or more in the absence of chemotherapy and/or hormonal treatment. ** Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 60. ** Radiation-induced oophorectomy with last menses > 1 year ago. ** Chemotherapy-induced menopause with > 1 year interval since last menses. ** 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.
  • Previous radiotherapy to thorax (prior breast radiation therapy [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 enrollment 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 electrocardiogram (ECG) with corrected QT (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.
  • Persistent toxicities (> Common Terminology Criteria for Adverse Event [CTCAE] grade 2) caused by previous cancer therapy, excluding alopecia.
  • Patients with myelodysplastic syndrome/acute leukemia 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.
  • 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), International Federation of Gynecology and Obstetrics (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.

Locations & Contacts

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025

New York

Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Rockville Centre
Memorial Sloan Kettering Rockville Centre
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To assess the safety of combining olaparib with low dose thoracic radiotherapy.

II. To establish the maximum tolerated dose (MTD) of olaparib with low dose thoracic radiotherapy.

SECONDARY OBJECTIVES:

I. To determine the cumulative incidence of locoregional recurrence within the radiation field at 6 months and 1 year.

II. To assess progression-free survival and overall survival at 6 months and 1 year.

III. To assess acute and chronic toxicities up to 1 year.

EXPLORATORY OBJECTIVES:

I. To evaluate exploratory biomarker correlates to clinical outcomes (as defined by OS and PFS): SLFN11 and PARP1 protein expression, gene expression by ribonucleic acid sequencing (RNA-Seq), homologous recombination deficiency and mutational burden/driver mutational status as evaluated by Memorial Sloan Kettering (MSK)-Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) and/or whole exome sequencing.

OUTLINE: This is a dose-escalation study of olaparib.

Participants receive olaparib orally (PO) twice daily (BID) for 3 weeks and undergo thoracic radiation therapy once daily (QD) 5 days a week for 2 weeks beginning the week after olaparib is started in the absence of disease progression or unacceptable toxicity.

After study completion of study treatment, patients are followed up at week 3 and at month 3, 6, 9, and 12.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Andreas Rimner

Trial IDs

Primary ID 18-195
Secondary IDs NCI-2018-01520
Clinicaltrials.gov ID NCT03532880