NCT02664181

Rational EpigenetiC Immunotherapy for SEcond Line Therapy in Patients With NSCLC: PRECISE Trial

Phase II Evaluation of Nivolumab, an Immune Checkpoint Inhibitor Alone or in Combination With Oral Decitabine/Tetrahydrouridine as Second Line Therapy for Non-small Cell Lung Cancer

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: Case Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to assess whether treatment with the study drug tetrahydrouridine-decitabine (THU-Dec) in combination with nivolumab is more effective than treatment with nivolumab alone in patients with NSCLC. Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1 (DNMT1). DNMT1 is an enzyme, or protein that causes chemical changes, often increased in cancer. Blocking DNMT1 has been shown to reduce tumor formation. Decitabine is experimental in this study because it is not approved by the Food and Drug Administration (FDA) for patients with lung cancer. Decitabine is approved by the FDA for treating patients with a blood disease called myelodysplastic syndrome (MDS, a condition where the bone marrow does not make blood cells normally). THU is an investigational (experimental) drug that works by blocking an enzyme that breaks down decitabine. This enzyme is highly expressed in solid tissues of the body, limiting the distribution of decitabine into these tissues, including solid cancer tissues. So, THU will increase the time cells are exposed to decitabine. The idea is that THU will also increase the time that the lung cancer cells are exposed to decitabine. THU is experimental because it is also not approved by the FDA, although it has been extensively used in clinical trials, including several cancer trials.

Detailed description

Primary objective: To determine if non-cytotoxic oral THU-Dec when combined with nivolumab can improve objective response rates of nivolumab Secondary objectives: i) To evaluate clinical efficacy end points and toxicity of oral THU-Dec when combined with nivolumab ii) evaluate the induction of a T-cell response in patients with metastatic NSCLC iii) To evaluate hypotheses regarding mechanisms of resistance and predictive biomarkers for response to nivolumab Study design: This is a Phase 2 randomized two arm trial of nivolumab alone or in combination with THU-Dec, in previously treated patients with stage IV Non-Small Cell Lung Cancer (NSCLC). The primary goal of this trial is to compare the efficacy of oral THU-Dec as a way of enhancing the anti-tumor immune response to nivolumab to that of nivolumab alone. The primary efficacy endpoint is overall RECIST-defined response. To accomplish this goal 60 patients will be randomized 2:1 to THU-Dec plus nivolumab or nivolumab only respectively.

Conditions

• Lung Cancer
• Non-small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Nivolumab	Nivolumab will be given at 3mg/kg by IV every two weeks until progression
DRUG	oral decitabine	oral decitabine \~0.2 mg/kg 60 minutes after the THU, twice weekly on consecutive days.
DRUG	Tetrahydrouridine	Oral THU \~10 mg/kg twice weekly on consecutive days

Timeline

• Start date: 2017-06-06
• Primary completion: 2019-07-02
• Completion: 2024-05-19
• First posted: 2016-01-26
• Last updated: 2024-09-03
• Results posted: 2020-12-10

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study