Clinical Trials /

Study of Olaparib and Temozolomide in Patients With Recurrent Small Cell Lung Cancer Following Failure of Prior Chemotherapy

NCT02446704

Description:

This research study is evaluating the combination of olaparib and temozolomide as a possible treatment for Small Cell Lung Cancer.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Olaparib and Temozolomide in Patients With Recurrent Small Cell Lung Cancer Following Failure of Prior Chemotherapy
  • Official Title: Phase I/II Study of Olaparib and Temozolomide in Patients With Recurrent Small Cell Lung Cancer Following Failure of Prior Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: 15-121
  • NCT ID: NCT02446704

Conditions

  • Small Cell Lung Cancer

Interventions

DrugSynonymsArms
OlaparibLynparzaOlaparib and Temozolomide
TemozolomideTemodar®Olaparib and Temozolomide

Purpose

This research study is evaluating the combination of olaparib and temozolomide as a possible treatment for Small Cell Lung Cancer.

Detailed Description

      This research study is a Phase I/II clinical trial, which has two parts. The participant will
      be asked to participate in one part of the study. The first part tests the safety of the
      combination of drugs and tries to define the appropriate dose to use for future studies. The
      second part tests whether the combination of drugs is effective in treating small cell lung
      cancer. "Investigational" means that the combination of drugs is being studied. It also means
      that the U.S. Food and Drug Administration (FDA) has not approved the combination of drugs
      for Small Cell Lung Cancer.

      Olaparib (Lynparza) is FDA approved for the treatment of a type of ovarian cancer associated
      with a particular DNA change. Olaparib works by blocking the activity of a protein called
      poly (ADP-ribose) polymerase (PARP) which is involved in DNA repair. Cancer cells rely on
      PARP to repair their DNA and enable them to continue dividing. Olaparib has been used in
      research studies with other cancers. Information from those other research studies suggests
      that this drug may help to treat patients with small cell lung cancer. While it is not
      approved by the FDA for small cell lung cancer, it is considered part of standard treatment
      for other cancer.

      Temozolomide (Temodar) is approved by the FDA for the treatment of a type of brain tumor,
      glioblastoma. It has been studied in small cell lung cancer in previous research studies.
      While it is not approved by the FDA for small cell lung cancer, it is considered part of
      standard treatment for relapsed disease.

      In this research study, the investigators are looking for the maximum tolerated dose or MTD
      of the combination of olaparib and temozolomide that can be given safely. The investigators
      will also begin to collect information about the effects of the combination on small cell
      lung cancer
    

Trial Arms

NameTypeDescriptionInterventions
Olaparib and TemozolomideExperimental- Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. Once the MTD is determined, the study will move to the phase II portion. Olaparib- Oral, on determined days per cycle Temozolomide- Oral, on determined days per cycle
  • Olaparib
  • Temozolomide

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must meet the following criteria on screening examination to be eligible to
             participate in the study. The eligibility criteria apply to both the phase I and phase
             II portions of the study.

          -  Participant must have histologically or cytologically confirmed small cell lung cancer
             and may not be a candidate for potentially curative therapy.

          -  Presence of measurable disease (RECIST 1.1): 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.

          -  The small cell lung cancer must have progressed radiographically following a
             platinum-based (cisplatin and/or carboplatin) standard prior chemotherapy regimen. Any
             number of interval prior lines of therapy is allowed. Patients who have received prior
             platinum-based chemotherapy and radiation for limited stage SCLC and have subsequently
             developed relapsed disease are eligible, as long as the platinum-based therapy was
             given within 12 months prior to the time of relapse.

          -  Participant (male/female) must be ≥18 years of age.

          -  Participant must have normal organ and bone marrow function measured within 28 days
             prior to administration of study treatment as defined below:

               -  Hemoglobin ≥ 10.0 g/dL

               -  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)

               -  AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal (unless liver
                  metastases are present in which case it must be ≤5 x ULN)

               -  Serum creatinine ≤1.5 x institutional upper limit of normal (ULN)

          -  ECOG performance status 0-1

          -  Participant must have a life expectancy ≥ 16 weeks.

          -  Women of childbearing potential must have a negative urine or serum pregnancy test
             within 28 days of initial dose of olaparib and temozolomide AND must agree to the use
             of two highly effective forms of contraception (see Section 5.5) throughout their
             participation in the study and for at least 3 months after the last dose of olaparib
             and temozolomide, OR confirmed prior to treatment on day 1 to be postmenopausal or
             surgically sterile. 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 sterilisation (bilateral oophorectomy or hysterectomy).

          -  Participant is willing to comply with the protocol for the duration of the study, and
             undergo treatment and scheduled visits and examinations including follow up.
             Participant must obtain prior approval from insurance to reimburse for oral
             temozolomide for the duration of the study or agree to self-pay for oral temozolomide.

        Exclusion Criteria:

          -  Participants who exhibit any of the following conditions at screening will not be
             eligible for admission into the study. The exclusion criteria apply to both the phase
             I and phase II portions of the study.

          -  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.

          -  Participation in another clinical study with an investigational product during the 21
             days prior to first dose of olaparib and temozolomide.

          -  Participants 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 for bone metastases, before and during the
             study as long as these were started at least 4 weeks prior to treatment with olaparib
             and temozolomide.

          -  Participants are to discontinue the use of the following classes of inhibitors of
             CYP3A4. Patients who are on these drugs are eligible if a washout period of a minimum
             of 7 days occurs before start of olaparib and temozolomide.

               -  Azole antifungals

               -  Macrolide antibiotics

               -  Protease inhibitors

          -  Persistent clinically significant toxicities (>=CTCAE v. 4.0 grade 2) caused by
             previous cancer therapy, with the exception of alopecia.

          -  Participants with a previously documented diagnosis of myelodysplastic syndrome (MDS)
             (or any dysplastic leukocyte morphology suggestive of MDS) or acute myeloid leukaemia.

          -  Participants with symptomatic uncontrolled brain metastases. Baseline brain imaging by
             CT or MRI is required for all patients. Participants with brain metastases that have
             been treated with prior radiation therapy and are stable on a subsequent scan are
             allowed. Participants with untreated possible brain metastases that are new at the
             time of screening and are < 1 cm and asymptomatic are allowed. The participant can
             receive corticosteroids as long as these were started and at a stable dose at least 28
             days prior to treatment.

          -  Major surgery within 14 days of starting study treatment and patients must have
             recovered from any effects of any major surgery.

          -  Participants 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, QTc prolongation > 470 msec, uncontrolled ventricular
             arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord
             compression (untreated and unstable for at least 28 days prior to study entry),
             extensive bilateral lung disease with less than 20% predicted lung function by DLCO
             (Lung Diffusion Capacity Testing), or any psychiatric disorder that prohibits
             obtaining informed consent.

          -  Participants unable to swallow orally administered medication and patients with
             gastrointestinal disorders likely to interfere with absorption of the study
             medication.

          -  Pregnant or Breast feeding women. All patients (male and female) must agree to
             practice a medically acceptable method of contraception as defined in section 5.5.
             Should a woman become pregnant or suspect that she is pregnant while participating in
             this study, she should inform her treating physician immediately.

          -  Patients who have a history of and are known to be serologically positive for human
             immunodeficiency virus (HIV) and are receiving antiviral therapy. Baseline testing is
             not required.

          -  Patients with known active Hepatitis B or C. Baseline testing is not required.

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

          -  Patients with uncontrolled seizures.

          -  Patients with second primary cancer, except: adequately treated non-melanoma skin
             cancer, curatively treated in-situ cancer of the cervix, or other solid tumors
             curatively treated with no evidence of disease for ≥ 5 years.

          -  Patients with current and symptomatic pneumonitis, or extensive bilateral lung disease
             on high resolution CT scan.

          -  Patients with whole blood transfusion in the last 120 days prior to entry to the
             study.

          -  Patients with previous allogeneic bone marrow transplant.

          -  Patients with active, uncontrolled infection.

          -  Patients who need to continue treatment with any prohibited medications listed in
             Section 5.6

          -  Patients who have not completed the appropriate washout period for the prohibited
             medications in Section 5.6
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:MTD of Olaparib and Temozolomide
Time Frame:2 Years
Safety Issue:
Description:Primary outcome measure for Phase 1 portion

Secondary Outcome Measures

Measure:Safety, assessed using CTCAE version 4.0 criteria
Time Frame:2 Years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:2 Years
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:2 Years
Safety Issue:
Description:
Measure:Methylation promoter methylation status
Time Frame:2 Years
Safety Issue:
Description:
Measure:PAR levels
Time Frame:2 Years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Small Cell Lung Cancer
  • SCLC

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