A Study of Galunisertib (LY2157299) in Combination With Nivolumab in Advanced Refractory Solid Tumors and in Recurrent or Refractory NSCLC or Hepatocellular Carcinoma.
- Conditions
- Advanced Refractory SolidTumours (Phase 1b) and in Recurrent or RefractoryNon–Small Cell Lung Cancer or Hepatocellular Carcinoma, (Phase 2)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-002093-20-DE
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 75
•For Phase 1b, must have advanced refractory solid tumors in any line of therapy. In the Phase 2 if fewer than 3 NSCLC, HCC or glioblastoma participants are not included in the Phase 1b, then a safety run-in must occur for any of the cohorts that have fewer than 3 participants in Phase 1.
•For Phase 2, must have one of the following tumor types: recurrent or refractory NSCLC (any histology) or HCC with elevated alpha-fetoprotein (AFP) =200 nanogram/milliliter (ng/mL)
•For Phase 2 only, have had disease progression or be refractory or intolerant to 1 prior line of therapy (first line therapy) for recurrent or refractory for NSCLC or HCC and have refused currently approved second-line therapy. First line therapy is defined as therapy used to treat advanced disease. This may include multiple chemotherapeutic, targeted or immunotherapeutic agents with or without radiation therapy and/or surgery. Each subsequent line of therapy is preceded by disease progression. A switch of an agent within the same drug class (eg, cisplatinum to carboplatinum) within a regimen in order to manage toxicity does not define the start of a new line of therapy.
•For NSCLC:
oPrior lines of therapy must include a platinum-based therapy. Investigational agents used in combination with standard therapies are allowed. Participants who received platinum-based neoadjuvant or adjuvant therapy and subsequently received platinum-based therapy as first-line therapy are eligible.
oParticipants who have completed neo-adjuvant or adjuvant therapy with a platinum doublet and have experienced disease recurrence within 6 months of completing the platinum doublet are eligible.
oTumors with driver mutations (epidermal growth factor receptor mutation positive or anaplastic lymphoma kinase fusion oncogene positive) treated with a tyrosine kinase inhibitor or crizotinib are eligible. For participants who have progressed on a tyrosine kinase inhibitor or crizotinib or are intolerant to this targeted therapy, that participant must receive platinum-based therapy prior to enrollment in this study. Documentation of such mutations must be available and entered into the electronic case report form (eCRF).
oMaintenance or switch maintenance therapy after first-line chemotherapy will be considered part of the first-line regimen and is acceptable.
Participants who completed and progressed on a platinum-containing regimen as adjuvant, neoadjuvant, or part of a course of chemoradiation therapy given from locally advanced disease and developed recurrent (local or metastatic) disease within the 6 months before screening would be counted as having received 1 prior platinum-containing regimen and therefore would not require re-treatment with a platinum-containing regimen for Stage IIIB, IV, or recurrent disease and are eligible. However, participants must have received at least 2 cycles of a platinum doublet based chemotherapy before discontinuation for toxicity. If participants received only one cycle of a platinum doublet and discontinue due to clear progression, that regimen should be counted as a prior line of therapy.
•For HCC:
oOne prior line of therapy which must include sorafenib or participant must have progressed or been intolerant to sorafenib for participants not eligible for transarterial chemoembolization. Participants who had sorafenib for locally advanced disease or are intolerant to sorafenib are eligible. Participants may have had clinical progression only foll
•Have moderate or severe cardiovascular disease:
oHave the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension.
oHave documented major electrocardiogram (ECG) abnormalities which are clinically significant at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrioventricular block, bundle-branch blocks, ventricular hypertrophy, or recent myocardial infarction).
oHave major abnormalities documented by Echocardiogram with Doppler (for example, moderate or severe heart valve function defect and/or left ventricular ejection fraction <50%, evaluation based on the institutional lower limit of normal).
oHave predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, personal history of aneurysm in any location, family history of aneurysms in any location, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computed tomography [CT] scan/magnetic resonance imaging [MRI] with contrast).
•Have evidence of interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity or active, noninfectious pneumonitis.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method