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

NCT02446704 | Unknown Phase 1 DMC

• 1 other identifier: 15-121
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Small Cell Lung Cancer

Keywords

Small Cell Lung Cancer; SCLC

Outcome Measures

Primary Outcomes (2)

• MTD of Olaparib and Temozolomide

  Primary outcome measure for Phase 1 portion

  2 Years

• Overall Response Rate for Olaparib and Temozolomide

  Primary outcome measure for Phase 2 portion

  2 Years

Secondary Outcomes (5)

• Safety, assessed using CTCAE version 4.0 criteria

  2 Years

• Overall Survival

  2 Years

• Progression Free Survival

  2 Years

• Methylation promoter methylation status

  2 Years

• PAR levels

  2 Years

Study Arms (1)

Olaparib and Temozolomide

EXPERIMENTAL

\- 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

Drug: Olaparib; Drug: Temozolomide

Interventions

Olaparib DRUG

Also known as: Lynparza

Olaparib and Temozolomide

Temozolomide DRUG

Also known as: Temodar®

Olaparib and Temozolomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zofia Piotrowska: lead
• AstraZeneca: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

olaparib; Temozolomide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Anna Farago, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: May 14, 2015
• First Posted: May 18, 2015
• Study Start: October 13, 2015
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2023
• Last Updated: February 7, 2022

Record last verified: 2022-01

Locations

US (3)