A Phase 1 Dose-Escalation and Pharmacokinetic Study of NC-4016 in Patients With Advanced Solid Tumors or Lymphoma

Lymphoma Clinical Trial

Official title:

A Phase 1 Dose-Escalation and Pharmacokinetic Study of NC-4016 in Patients With Advanced Solid Tumors or Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01999491
• Other study ID #: 2013-0466
• Secondary ID: NCI-2014-00555
• Status: Active, not recruiting
• Phase: Phase 1
• First received: November 26, 2013
• Last updated: April 19, 2017
• Start date: November 4, 2013
• Est. completion date: November 2018

Study information

• Verified date: April 2017
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Study Groups:

If you are found to be eligible to take part in this study, you will be enrolled in either a dose escalation group or the dose expansion group.

Dose Escalation:

If you are in a dose escalation group, you will be assigned to a dose level based on when you 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:

If you are in the dose expansion group, you will receive NC-4016 at the highest dose that was tolerated in the escalation groups.

Study Drug Administration:

Each study cycle is 21 days.

On Day 1 of each cycle, you will receive NC-4016 by vein over 2 hours.

You will be given standard drugs to help decrease the risk of side effects. You may ask the study staff for information about how the drugs are given and their risks.

If you have a severe side effect, your dose of study drug may be delayed.

Study Visits:

On Day 1 of each cycle:

• You will have a physical exam.

• Your vital signs (blood pressure, heart rate, breathing rate, and temperature) will be monitored every 20 minutes during the infusion and 1 hour after the end of the infusion during Cycle 1 and right before and at the end of the infusion for all other cycles.

• Blood (about 3 teaspoons) will be drawn for routine tests.

• You will have a neurological exam and electromyogram.

• You will have an EKG before the start of the infusion, at the end of the infusion, and 1 hour after the end of the infusion (Cycle 1 and 2 only). After Cycle 1, you will only have 1 EKG before dosing.

On Days 8 and 15 of each cycle, blood (about 3 teaspoons) will be drawn for routine tests.

On Day 2 of Cycle 1 you will have an EKG corresponding to the 24 hour PK testing.

Every 3 cycles (every 9 weeks):

• You will have an x-ray, CT, MRI, or PET scan to check the status of the disease.

• If you have lymphoma, you will have a bone marrow biopsy to check the status of the disease.

• You will have a nerve conduction evaluation.

• If the doctor thinks it is needed, blood (about 1 teaspoon) will be drawn for tumor marker testing.

PK Testing:

Blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing. PK testing measures the amount of study drug in the body at different time points.

• On Day 1 of Cycles 1 and 3, blood will be drawn before, then at 0.5, 1, and 2 hours during the infusion, and then 9 more times up to 12 hours after you receive the study drug (13 draws total each day).

• On Days 2, 3, 4, 6, 8, and 15 of Cycles 1 and 3, blood will be drawn 1 time after you receive the study drug.

• On Day 1 of Cycles 2 and Cycle 4, blood will be drawn 1 time before you receive the study drug.

Urine Collection:

Urine will be collected for PK testing at the following time points during Cycles 1 and 3:

• Before you receive the study drug

• 0-2 hours (during the infusion)

• 2-4 hours after you received the study drug

• 4-8 hours after you received the study drug

• 8-12 hours after you received the study drug

• 12-24 hours after you received the study drug

You will collect your urine at home over 24 hours during the following times after you received the study drug:

• Days 1-2

• Days 2-3

• Days 7-8

• Days 14-15

• Days 21-22

Your study doctor will provide you with urine collection bottles. Your urine samples will contain a very small amount of platinum from the study drug. This is not considered to be a risk to you, but as a precaution, the urine collection containers should only be handled by you, and the containers will be labeled as a "Bio-Hazard".

If you have a severe side effect, you may have extra tests until the side effects have gotten better.

Length of Study:

You may continue taking the study drug for as long as you are benefitting. You will be taken off study early if the disease gets worse, intolerable side effects occur, you develop new health problems, your doctor thinks that it is no longer in your best interest to receive the study drug, or if you are unable to follow study directions.

Your participation on the study will be over after the end-of-dosing visit.

End-of-Dosing Visit:

Within 28 days after the last dose of NC-4016:

• You will have a physical exam.

• You will have a neurological exam and an electromyogram.

• You will have a chest x-ray.

• You will have an x-ray, CT scan, MRI scan, or PET scan, or a bone marrow biopsy if you have lymphoma, to check the status of the disease.

• Blood (about 3 teaspoons) and urine will be collected for routine tests.

• You will have an EKG and an ECHO or MUGA.

• If the doctor thinks it is needed, blood (about 1 teaspoon) will be drawn for tumor marker testing.

This is an investigational study. NC-4016 is not commercially available or FDA approved. It is currently being used for research purposes only. The study doctor can explain how NC-4016 is designed to work.

Up to 40 participants will be enrolled in this study. All will be enrolled at MD Anderson.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 39
• Est. completion date: November 2018
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Have signed written informed consent prior to the initiation of any study-specific procedures

2. Be a male or female 18 years or older

3. Have a histologically or cytologically confirmed diagnosis of advanced solid tumor or lymphoma, or primitive hepatocarcinoma with radiological diagnosis

4. Have advanced or metastatic disease refractory to standard curative or palliative therapy or contraindication to standard therapy

5. Have an ECOG performance status of 0-2

6. 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)

7. 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

8. Have adequate renal function: glomerular filtration rate >=50 mL/min (calculated according to the formula of Cockcroft and Gault)

9. 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

10. 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)

11. 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:

1. 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

2. 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

3. 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

4. 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

5. Have known hypersensitivity to Pt compounds

6. 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

7. Is pregnant or breast-feeding

8. 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

9. 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

10. Have known hepatitis B or C, or human immunodeficiency virus infection

11. 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

Related Conditions & MeSH terms

• Advanced Cancers
• Lymphoma

Intervention

Drug:
• NC-4016
Dose Escalation Group Starting Dose: 15 mg/m2 by vein on Day 1 of a 21 Day cycle. Dose Expansion Group Starting Dose: Maximum tolerated dose from Dose Escalation Group.

Locations

Country	Name	City	State
United States	University of Texas MD Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	NanoCarrier Co., Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) of NC-4016	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.	21 days
Secondary	Pharmacokinetic (PK) and Free (Ultrafiltrate) Platinum (Pt) Following Single and Multiple Infusions of NC-4016 Determined for the Cycle 1 and 3 Infusions in all Participants.		During the First 4 Cycles of Treatment
Secondary	Excretion Profile of Total and Free (Ultrafiltrate) Platinum (Pt) Following Single and Multiple Infusions of NC-4016 Collected at Various Time Points During Cycle 1 and Cycle 3.		Various Time Points During Cycle 1 and Cycle 3

External Links

•   University of Texas MD Anderson Cancer Center Website