Small Cell Lung Cancer
Conditions
Keywords
Small Cell Lung Cancer, SCLC
Brief summary
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
Interventions
DRUGOlaparib
DRUGTemozolomide
Sponsors
AstraZeneca
Zofia Piotrowska
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MTD of Olaparib and Temozolomide | 2 Years | Primary outcome measure for Phase 1 portion |
| Overall Response Rate for Olaparib and Temozolomide | 2 Years | Primary outcome measure for Phase 2 portion |
Secondary
| Measure | Time frame |
|---|---|
| Progression Free Survival | 2 Years |
| Safety, assessed using CTCAE version 4.0 criteria | 2 Years |
| PAR levels | 2 Years |
| Methylation promoter methylation status | 2 Years |
| Overall Survival | 2 Years |
Countries
United States
Outcome results
None listed