Clinical Trial 19177

Cancer Type:
Interventions:AZD2171 (Cediranib); Cediranib (Recentin); Olaparib (Lynparza); Paraplatin (carboplatin); carboplatin; cisplatin; etoposide

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Alberto Chiappori

Overview

Study Title

A Phase II Study of Olaparib Plus Cediranib in Combination with Standard Therapy for Small Cell Lung Cancer

Summary

The purpose of this study is to test two things: (1) Compare any good and bad effects of using cediranib with the usual chemotherapy for SCLC (carboplatin/cisplatin and etoposide) (2) Compare any good and bad effects of adding olaparib and cediranib after the completion of chemotherapy (what is called maintenance therapy) to the usual method, which is no maintenance therapy after completion of chemotherapy.

Objective

To determine whether the addition of cediranib plus olaparib as maintenance therapy in small cell lung cancer (SCLC) leads to improved progression-free survival (PFS) compared to standard therapy (no maintenance treatment) utilizing RECIST version 1.1 criteria.

Inclusion Criteria

  • Histologically or cytologically confirmed diagnosis of extensive-stage small cell lung cancer with no prior systemic treatment
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • Eastern Cooperative Oncology Group (ECOG) performance status equal to or less than 2 (Karnofsky >= 60%)
  • Adequate renal, hepatic and bone marrow function
  • White blood cell count (WBC) >= 3 x 10^9/L
  • No features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) on peripheral blood smear
  • Ability to swallow and retain oral medication
  • Women of child-bearing potential and male patients and their partners who are sexually active must agree to use two highly effective forms of contraception in combination for the duration of study participation and for 3 months after completion of olaparib and cediranib administration.
  • Ability to understand and the willingness to sign a written informed consent document
  • Participants must have archival tumor tissue available for analysis (minimum 20 5 um slide) or be able to undergo a baseline fresh tumor tissue biopsy
  • Adequately controlled blood pressure
  • Adequately controlled thyroid function

  • Exclusion Criteria

  • Have had major surgery or trauma within 28 days prior to entering the study; patients must have recovered from any effects of any major surgery and surgical wound should have healed prior to starting treatment
  • Have had radiotherapy within 14 days prior to entering the study
  • A non-healing wound, fracture, or ulcer
  • Have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Common Terminology Criteria for Adverse Events [CTCAE] grade 1 or baseline, with the exception of alopecia)
  • Are receiving any other investigational agents
  • Symptomatic central nervous system (CNS) metastases or leptomeningeal carcinomatosis
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib, cediranib, carboplatin, cisplatin, or etoposide
  • A history of myelodysplastic syndrome (MDS)
  • A history of acute myeloid leukemia (AML), or a history of any other primary malignancy within 3 years prior to initiation of treatment on this study; exceptions include: patients with a history of malignancies (other than AML) that were treated curatively and have not recurred within 3 years prior to study entry; resected basal and squamous cell carcinomas of the skin; and completely resected carcinoma in situ of any type
  • Clinically significant gastrointestinal abnormalities
  • A history of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or insufficiently treated deep venous thrombosis (DVT) within the past 3 months; Note: Participants with recent DVT who have been treated with therapeutic anti-coagulants for at least 6 weeks are eligible, with the exception of participants being treated with warfarin, which is prohibited on this study; other oral anti-coagulants may be allowed after discussion with overall principle investigator (PI), but short half-life low molecular weight heparins are strongly preferred
  • Evidence of active bleeding diathesis
  • Hemoptysis in excess of 2.5 mL within 6 weeks prior to the first dose of study medication
  • Patients receiving any medications or substances that are potent inhibitors or inducers of CYP3A4 are ineligible; the required washout period for strong inhibitors is 2 weeks and at least one week for moderate inhibitors; the required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 4 weeks for other agents
  • Require concomitant therapy with phenytoin, phenobarbital, arbamazepine, or valproic acid
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Women who are pregnant; breastfeeding should be discontinued if the mother is treated with olaparib or cediranib
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Participants must be willing and able to check and record daily blood pressure readings if receiving cediranib