SGI-110 Plus Durvalumab/Tremelimumab in SCLC
Condition: Extensive-stage Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine if a combination of investigational agents is safe
      to give to people with small cell lung cancer (SCLC) after standard chemotherapy has been
      attempted. Subjects enrolled in this trial will receive 3 investigational drugs: SGI-110
      (guadecitabine), durvalumab (MEDI4736) and tremelimumab.
    

Detailed description: 
      SCLC accounts for approximately 15% of new cases of lung cancer, and an estimated 33,000
      cases are expected to be diagnosed in the United States in 2016. Compared to NSCLC, SCLC
      typically has a more rapid doubling time, a higher growth fraction, and earlier development
      of distant metastases. Patients with limited stage (LS) disease are treated with curative
      intent using definitive, concurrent chemotherapy and thoracic radiotherapy. For patients with
      extensive stage (ES) disease, systemic chemotherapy can prolong survival in most cases,
      however long-term survival is rare. Despite the activity of several agents in SCLC, an
      etoposide plus platinum (i.e. cisplatin) doublet regimen remains the standard of care in the
      first-line setting because of its higher activity compared to other chemotherapy regimens, as
      well as the ease of combining it with radiation. Initial response rates may be as high as
      70-90% in LS-SCLC and 50-70% in ES-SCLC. However, the disease typically recurs rapidly which
      is reflected by median survival rates of 9 to 11 months for ES-SCLC and a 2-year survival
      rate of less than 5%.

      This study has a 3 + 3 design that will be used to assess the safety of SGI-110 given prior
      to flat doses of durvalumab (1500 mg) and tremelimumab (75 mg). The starting dose of SGI-110
      will be 30 mg/m2 (dose level 0) and the target dose that is predicted to be safe and most
      effective will be 45 mg/m2 (dose level 1). These doses have been chosen based on safety and
      efficacy data from phase 1 clinical trials in other solid tumors, as described above.
      Patients enrolled in any given dose level will be evaluated for safety (adverse events
      monitoring) and efficacy. There will be mandatory pre- and on-treatment tumor biopsies
      performed in alternating fashion on cycle 1 day 8 +/- 2 days or cycle 2 day 8 +/- 2 days. The
      dose-limiting toxicity (DLT) observation period will last for 4 weeks (28 days) and ends on
      C2D1. Delayed serious immune-mediated adverse events will also be monitored but will not be
      considered dose limiting toxicities.
    

Intervention name(s): Durvalumab; Tremelimumab; SGI-110
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 1500 mg IV on day 8 (flat dose) until progression; 75 mg IV on day 8 (flat dose) x 4 doses; SC daily for 5 days (days 1-5) until progression or toxicity
Dose escalation scheme:
Dose level -1 - SGI-110 20 mg/m2 SC daily; Dose level 0 - SGI-110 30 mg/m2 SC daily; Dose level 1 - SGI-110 45 mg/m2 SC daily; and SGI-110 given on days 1-5 of every 28 day cycle
Other intervention name(s): MEDI4736; CP-675,206; Guadecitabine
Intervention MeSH terms: Durvalumab; Tremelimumab; Guadecitabine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment