Study of NK012 and 5-FU/LV in Solid Tumors Followed by Dose Expansion in Colorectal Cancer

NCT01238939 | Completed Phase 1

• 1 other identifier: A6012113US
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective is to determine the maximum tolerated dose/recommended phase II dose of the combination regimen of NK012 and 5-fluorouracil in patients with advanced solid tumors.

Conditions

Advanced Solid Tumors; Metastatic Colorectal Cancer

Keywords

solid tumors; colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Number of patients with dose-limiting toxicity as determinant of the maximum tolerated dose/recommended dose

  From date of first dose to off-study (or 30 days since last dose)

Secondary Outcomes (4)

• Number of patients with adverse events as a measure of safety and tolerability

  From date of first dose to off-study (or 30 days since last dose)

• Tumor measurements, as a measure of efficacy

  Baseline, then every on average every 2 months until off-study

• Area under the plasma concentration versus time curve (AUC) of NK012 and fluorouracil

  15,30min, 1,6,24,46.5,48,72hrs, Wk1,2,3,4 of cycle 1

• Peak Plasma Concentration (Cmax) of NK012 and fluorouracil

  15,30min, 1,6,24,46.5,72hrs, week 1,2,3,4 of cycle 1

Study Arms (1)

Treatment

EXPERIMENTAL

Drug: NK012 and 5-FU

Interventions

NK012 and 5-FU DRUG

NK012 infusion on Day 1 of each 28 day cycle 5-FU continuous infusion on Days 1 and 15 of each 28 day cycle

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of advanced solid tumor for which no efficacious therapy exists, or for which a camptothecin-based regimen would be appropriate.
• For the dose expansion at MTD/RD only:
• The patient must have failed oxaliplatin-based first line therapy for metastatic colorectal cancer. This includes patients who failed oxaliplatin-based therapy with progressive disease, as well as patients who, based on toxicity or MD/patient discretion, are no longer candidates for oxaliplatin. Patients who failed adjuvant therapy with oxaliplatin-based chemotherapy regimens within one year of last dose of oxaliplatin-based chemotherapy will also be considered eligible for this study.
• Patients must have had no more than one prior chemotherapy regimen in the metastatic setting. Patients who had radiosensitizing chemotherapy during radiation treatment will not have this treatment count as a prior chemotherapy regimen.
• Patients must have measurable disease by RECIST (version 1.1).
• Patient must have recovered from all acute adverse effects of prior therapies, excluding alopecia.
• For patients enrolled in the dose escalation phase, no more than 4 prior cytotoxic regimens in the metastatic setting.
• Prior irradiation to no more than 25% of the bone marrow.
• ECOG performance status of 0-1.
• Life expectancy of at least 12 weeks.
• Patients are at least 18 years of age.
• Adequate bone marrow function as defined by ANC ≥ 1500/mm\^3 and platelet count ≥ 100,000/mm\^3.
• AST and ALT ≤ 3.0 x ULN (5 x ULN if documented liver metastases) and total bilirubin ≤ 1.5 x ULN.
• Serum creatinine ≤ 1.5 x ULN, or creatinine clearance ≥ 60 mL/min by Cockcroft-Gault formula\* for patients with serum creatinine \> 1.5 x ULN.
• \*Cockcroft-Gault formula for creatinine clearance (CrCl): Males: CrCl (ml/min) = (140 - age) x wt (kg) / (serum creatinine x 72) Females: Multiply the above result by 0.85

You may not qualify if:

• Prior chemotherapy, radiation therapy, or investigational therapy within 4 weeks (exception: 6 weeks for nitrosoureas or mitomycin C); or prior non-cytotoxic therapy within 5 drug half-lives (or 4 weeks, which ever is shorter); or monoclonal antibodies within 4 weeks prior to the first dose of study treatment.
• Concurrent use of other investigational agent.
• History of brain metastases or spinal cord compression, unless irradiated or treated a minimum of 4 weeks prior to first study treatment and stable without requirement of corticosteroids for \> 1 week.
• Concurrent serious infections requiring parenteral antibiotic therapy.
• Pregnant or of childbearing potential and not using methods to avoid pregnancy. A negative pregnancy test must be documented at baseline for women of childbearing potential. Patients may not breast-feed infants while on this study.
• Significant cardiac disease including heart failure that meets NYHA class III and IV definitions, history of myocardial infarction within 6 months of study entry, uncontrolled dysrhythmias or poorly controlled angina.
• History of serious ventricular arrhythmia (VT or VF, ≥ 3 beats in a row), QTc ≥ 450 msec for men and 470 msec for women, or LVEF ≤ 40% by MUGA or ECHO.
• History of allergic reactions attributed to compounds of topoisomerase I inhibitors.
• Prior treatment with irinotecan.

Sponsors & Collaborators

• Nippon Kayaku Co., Ltd.: lead

Study Sites (1)

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2010
• First Posted: November 11, 2010
• Study Start: August 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: March 1, 2014
• Last Updated: November 13, 2014

Record last verified: 2014-11

Locations

US (1)