Advanced solid tumors and first-line metastatic squamous NSCLC
Conditions
Interventions
Product Name: Nanoparticle Cisplatin
Product Code: NC-6004
Pharmaceutical Form: Infusion
INN or Proposed INN: Not available
Current Spon
Sponsors
NanoCarrier Co, Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provide signed written informed consent prior to the initiation of any study-specific procedures. 2. (Part 2 only) Cohort 1: Have histologically or cytologically confirmed diagnosis of Stage IV squamous NSCLC and have not received prior chemotherapy for metastatic disease. Patients with known sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) fusion oncogene must have received at least 1 and up to 2 targeted therapies prior to enrollment. - A patient with stable, treated brain metastases is eligible, provided that there is no evidence of progression after treatment and the patient does not require corticosteroids, or, if the patient requires corticosteroid, has been receiving a stable dose of corticosteroids for at least 14 days prior to assignment to treatment. - Patients whose tumors are known to harbor an exon 19 deletion or exon 21 L858R EGFR mutation must have had intolerance or have progressed on at least 1 and up to 2 EGFR tyrosine kinase inhibitors. - Patients whose tumors are known to harbor an ALK translocation must have had intolerance or have progressed on at least 1 and up to 2 ALK inhibitors. (Part 2 only) Cohort 2: Have histologically or cytologically confirmed diagnosis of nonresectable, recurrent, or metastatic biliary tract carcinoma (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, or ampullary carcinoma) and have not received prior systemic anticancer therapy for advanced or metastatic disease. (Part 2 only) Cohort 3: Have histologically or cytologically confirmed diagnosis of metastatic or locally advanced TCC of the urinary tract (bladder, urethra, ureter, renal pelvis) (T3b-T4 N0 M0, Tany N1-N3 M0, or Tany Nany M1) and are not candidates for surgery. - Patients must not have received prior treatment with systemic anticancer therapy for metastatic or locally advanced urinary tract cancer. - Certain mixed histologies that are predominantly (>50%) TCC are eligible: squamous, adenocarcinoma, and undifferentiated. Mixed undifferentiated histology requires immunohistochemistry consistent with a TCC origin. Predominantly squamous or neuroendocrine tumors are excluded. 3. Have measurable disease per RECIST version 1.1. 4. Are males or females aged =18 years. 5. Have an ECOG performance status of 0 to 1. 6. Have adequate bone marrow reserve defined as: - Absolute neutrophil count of at least 1.5 × 109/L, - Platelet count of at least 100 × 109/L, and - Hemoglobin level of 10 g/dL (transfusion is allowed to achieve hemoglobin level of at least 10 g/dL). 7. Have adequate liver function defined as:
Exclusion criteria
Exclusion criteria: 1. Have received prior platinum therapy in the past 3 months (Part 1) or 6 months in the adjuvant or neoadjuvant setting (Part 2). 2. Have received prior cisplatin and gemcitabine concomitantly within the last 6 months or are refractory to cisplatin and gemcitabine. 3. Are unable to receive platinum-based therapy due to previous toxicity. 4. Have unresolved toxicity from prior radiation, chemotherapy, or other targeted treatment, including investigational treatment, with the exception of alopecia and =Grade 1 peripheral neuropathy according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 (National Cancer Institute 2010). Clinical judgment by the investigator is allowed to determine if Grade 1 fatigue at screening is residual toxicity from prior treatment or is a symptom of the patient’s general condition or disease. The investigator and Medical Monitor will discuss the eligibility of patients with baseline toxicity 5. Have evidence suggesting pulmonary fibrosis or interstitial pneumonia. 6. Have a history of thrombocytopenia with complications including hemorrhage or bleeding of =Grade 2 according to the NCI CTCAE version 4.03 that required medical intervention or have any hemolytic condition or coagulation disorders that would make participation unsafe in the opinion of the investigator. 7. Have known hypersensitivity to platinum compounds or gemcitabine. 8. Have uncontrolled diabetes or have hypertension requiring more than 3 medications for control of hypertension. 9. Are pregnant or breast-feeding. 10. Have signs or symptoms of organ failure, major chronic illnesses other than cancer, or any concomitant medical or social conditions that, in the opinion of the investigator, make it undesirable for the patient to participate in the study or that could jeopardize compliance with the protocol. 11. Have experienced any of the following within the 6-month period prior to screening: angina pectoris, coronary artery disease or cerebrovascular accident, transient ischemic attack, cardiac failure with known ejection fraction less than 40%, or cardiac arrhythmia requiring medical therapy. 12. Are unwilling or unable to comply with study procedures or are planning to take a vacation for 7 or more consecutive days during the treatment phase of the study without prior consent from the Medical Monitor.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In the expansion phase of the study (Part 2), to evaluate the activity of NC-6004 in combination with gemcitabine in patients with first-line Stage IV squamous NSCLC, first-line advanced or metastatic biliary tract cancer, and first-line metastatic or locally advanced bladder cancer compared with historical control as measured by local investigator/radiologist-assessed progression-free survival (PFS), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.; Secondary Objective: - To evaluate ORR, DCR (DCR = complete response [CR] + partial response [PR] + stable disease [SD]), DOR, PFS, and OS; - To evaluate therapy-related AEs; - To evaluate the safety and tolerability of NC-6004 when combined with gemcitabine; - To evaluate QoL using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30); - To evaluate acute and delayed symptoms using the MD Anderson Symptom Inventory (MDASI) and a nausea and vomiting patient diary. ;Primary end point(s): The primary endpoint progression-free survival (PFS), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. will be continuously updated and compared with the historical PFS from Phase 3 pivotal cisplatin and gemcitabine trials within each cohort. The PFS hazard model will be updated as PFS data accrue. A hazard ratio (HR) for PFS for each cohort versus historical control will be obtained.;Timepoint(s) of evaluation of this end point: Progression-free survival will be defined as the time from first dose of study product until the first date of either disease progression or death due to any cause and will be evaluated for each dose level and for all patients in the FAS. The date of disease progression will be defined as the earliest date of radiological disease progression as assessed by the investigator using RE | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The exploratory endpoints of this study include exploratory safety endpoints of the occurrence of AEs and SAEs after 6 cycles of treatment and the following PK endpoints for micellar platinum in plasma and total platinum in plasma and plasma ultrafiltrate calculated for all patients using noncompartmental analysis: Cmax (maximum concentration) Tmax (time to maximum concentration) AUClast (area under the concentration-time curve from time zero to the last quantifiable concentration) AUC0-t (area under the concentration-time curve from time zero to the end of the dosing interval) AUC0-8 (area under the concentration-time curve from time zero to infinity) AI (accumulation index) Vss (volume of distribution at steady-state) MRT (mean residence time) ?z (terminal elimination phase rate constant) T½ (terminal half-life) CL (clearance) Vz (volume of distribution) - Safety endpoints: The safety endpoints for this study are the incidence and severity of AEs and laboratory abnormalities, according to the NCI CTCAE version 4.03, the occurrence of SAEs and treatment discontinuations due to AEs, and nausea severity and vomiting incidence obtained from the patient diary. - Efficasy analysis. ; Timepoint(s) of evaluation of this end point: Pharmacokinetic plasma and plasma ultrafiltrate will be collected at the following times in Part 2 for up to 6 cycles: • Before the start of the NC-6004 infusion on Day 1 • At the end of NC-6004 infusion • Before gemcitabine infusion on Day 8 • At End-of-Treatment visit Adverse events will be evaluated at each visit during every cycle and graded according to th | — |
Countries
Bulgaria, Italy, Poland, Romania, United States
Contacts
Public ContactPeter Mascenik
PPD, Inc.
Outcome results
None listed