A Phase 1 Dose-Escalation and Pharmacokinetic Study of NC-4016 in Patients With Advanced Solid Tumors or Lymphoma
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- NanoCarrier Co., Ltd.
- Enrollment
- 34
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose (MTD) of NC-4016
Study Overview
Brief Summary
The goal of this clinical research study is to find the highest tolerated dose of NC-4016 that can be given to patients with advanced solid tumors or lymphoma. The safety of the drug will also be studied.
Detailed Description
Study Groups:
If participants are found to be eligible to take part in this study, they will be enrolled in either a dose escalation group or the dose expansion group.
Dose Escalation:
If participants are in a dose escalation group, they will be assigned to a dose level based on when they joined this study. Up to 6 dose levels of NC-4016 will be tested and at least 3 patients will be enrolled at each dose level. The first group of participants will receive the lowest dose level of NC-4016. Each new group will receive a higher dose of NC-4016 than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of NC-4016 is found.
Dose Expansion:
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Have signed written informed consent prior to the initiation of any study-specific procedures
- •Be a male or female 18 years or older
- •Have a histologically or cytologically confirmed diagnosis of advanced solid tumor or lymphoma, or primitive hepatocarcinoma with radiological diagnosis
- •Have advanced or metastatic disease refractory to standard curative or palliative therapy or contraindication to standard therapy
- •Have an ECOG performance status of 0-2
- •Have adequate bone marrow reserve: a. Absolute neutrophil count at least 1.5 x 10^9/L, b. Platelet count at least 100 x 10^9/L, and c. Hemoglobin at least 10 g/L (transfusion is allowed to achieve hemoglobin of 10 g/L)
- •Have adequate liver function: a. Total serum bilirubin no more than 1.5 x upper limit of normal (ULN), and b. Alanine aminotransferase and aspartate aminotransferase<= 2.5 x ULN or <= 5.0 x ULN in case of documented hepatic metastasis
- •Have adequate renal function: glomerular filtration rate >=50 mL/min (calculated according to the formula of Cockcroft and Gault)
- •Be reasonably recovered from preceding major surgery as judged by the investigator or no major surgery within 4 weeks prior to the start of Day 1 treatment
- •Have a negative pregnancy test for females at screening, preferably done within 1 week before Day 1 of treatment (not applicable to patients with bilateral oophorectomy and/or hysterectomy)
- •Be willing to abstain from heterosexual activity or practice physical barrier contraception from study entry to 6 months after the last day of treatment
Exclusion Criteria
- •Have peripheral neuropathy of Grade 3 or Grade 4 at screening, according to National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE)v4.03, 14 June 2010 scale; or TNSc score greater than 4
- •Have an interval from previous neurotoxic platinums of less than 6 months and/or from previous other neurotoxic drugs less than 3 months (eg, taxanes) unless reasonably recovered from all grades of neurotoxicity as judged by the investigator
- •Have a history of thrombocytopenia with complications including hemorrhage or bleeding >= Grade 2 using NCI CTCAE v4.03, 14 June 2010 that required medical intervention or any hemolytic condition or coagulation disorders that would make participation unsafe in the opinion of the investigator
- •Have unresolved toxicity from previous treatment or previous investigational agents; excluding alopecia. 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
- •Have known hypersensitivity to Pt compounds
- •Have received investigational agents or systemic anticancer agents (other than neurotoxic compounds) within 14 days of Day 1 of treatment, or 28 days for those agents with unknown elimination half-lives, or known elimination half-lives greater than 50 hours; or 6 weeks for mitomycin C or for nitrosourea agents
- •Is pregnant or breast-feeding
- •Have signs or symptoms of end organ failure, major chronic illnesses other than cancer, or any severe concomitant conditions which, in the opinion of the investigator, make it undesirable for the patient to participate in the study, or which could jeopardize compliance with the protocol
- •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
- •Have known hepatitis B or C, or human immunodeficiency virus infection
- •Is unwilling or unable to comply with study procedures, or is planning to take a vacation for 7 or more consecutive days during the treatment phase of the study
Arms & Interventions
NC-4016
Dose Escalation Group: NC-4016 will be administered as 2-hour intravenous infusion once every 3 weeks. Initial dose level 15 mg/m2. The dose level of NC-4016 in subsequent cohorts determined by the toxicity profile of the previous cohort, and dose level increased to 25, 30, 40, 60, and 80 mg/m2 or higher at each subsequent cycle until the highest dose level is reached or DLT prohibits further dose-level escalation. Dose level 1 will be the starting dose level (DL). If 2 out of the first 3 patients enrolled at DL1 experience a DLT during Cycle 1 or Cycle 2,then the next cohort of patients will be enrolled at DL0 (10 mg/m2).
Dose Expansion Group: Maximum tolerated dose from Dose Escalation Group
Intervention: NC-4016 (Drug)
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD) of NC-4016
Time Frame: 21 days
MTD defined as the highest dose level at which no more than 1 of 6 dose limiting toxicity (DLT) evaluable patients experience a DLT during Cycle 1 of dosing. DLT determined by NCI CTCAE v4.03, 14 June 2010.
Secondary Outcomes
- T1/2(During the First 4 Cycles of Treatment (each cycle is 21 days))
- AUC(During the First 4 Cycles of Treatment (each cycle is 21 days))
- Vz(During the First 4 Cycles of Treatment (each cycle is 21 days))
- Excretion Profile of Total and Free (Ultrafiltrate) Platinum (Pt)(Cycle 1 and Cycle 3 (each cycle is 21 days))
- Cmax(During the First 4 Cycles of Treatment (each cycle is 21 days))
- Tmax(During the First 4 Cycles of Treatment (each cycle is 21 days))
- CL(During the First 4 Cycles of Treatment (each cycle is 21 days))
- Vss(During the First 4 Cycles of Treatment (each cycle is 21 days))