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A Phase I Study of NK012 in Combination With Infusional 5-fluorouracil and Leucovorin in Patients With Advanced Solid Tumors Followed by a Dose Expansion Phase in Patients With Metastatic Colorectal Cancer

Phase 1
18 Years
Open (Enrolling)
Advanced Solid Tumors, Metastatic Colorectal Cancer

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Trial Information

A Phase I Study of NK012 in Combination With Infusional 5-fluorouracil and Leucovorin in Patients With Advanced Solid Tumors Followed by a Dose Expansion Phase in Patients With Metastatic Colorectal Cancer

On Day 1 of each 28 day cycle, NK012 will be administered as a 30 minute IV infusion,
followed by continuous infusion of 5-FU over 46 hours. On Day 15 of each cycle, patients
again receive 5-FU continuous infusion. Treatment is expected to continue for 6 cycles,
unless disease progression or the development of unacceptable toxicity requires
discontinuation of the drug. At the discretion of the investigator, patients who show signs
of benefit may continue beyond 6 cycles.

Once a MTD/RD has been determined for the combination regimen, a dose expansion cohort of
patients with metastatic colorectal cancer will be treated at the determined MTD.

(Prior to Amendment 2, patients were receiving NK012 and 5-FU and leucovorin (LV). The
dosing regimen was changed as of Amendment 2 to NK012 and 5-FU.)

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of advanced solid tumor for which
no efficacious therapy exists, or for which a camptothecin-based regimen would be

2. For the dose expansion at MTD/RD only:

1. 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.

2. 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

3. Patients must have measurable disease by RECIST (version 1.1).

3. Patient must have recovered from all acute adverse effects of prior therapies,
excluding alopecia.

4. For patients enrolled in the dose escalation phase, no more than 4 prior cytotoxic
regimens in the metastatic setting.

5. Prior irradiation to no more than 25% of the bone marrow.

6. ECOG performance status of 0-1.

7. Life expectancy of at least 12 weeks.

8. Patients are at least 18 years of age.

9. Adequate bone marrow function as defined by ANC ≥ 1500/mm^3 and platelet count ≥

10. AST and ALT ≤ 3.0 x ULN (5 x ULN if documented liver metastases) and total bilirubin
≤ 1.5 x ULN.

11. 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

12. Able to understand and show willingness to sign a written informed consent document.

Exclusion Criteria:

1. 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.

2. Concurrent use of other investigational agent.

3. 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.

4. Concurrent serious infections requiring parenteral antibiotic therapy.

5. 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.

6. 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.

7. 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.

8. History of allergic reactions attributed to compounds of topoisomerase I inhibitors.

9. Prior treatment with irinotecan.

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

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

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

August 2010

Completion Date:

December 2014

Related Keywords:

  • Advanced Solid Tumors
  • Metastatic Colorectal Cancer
  • solid tumors
  • colorectal cancer
  • Colorectal Neoplasms
  • Neoplasms



Sarah Cannon Research Institute Nashville, Tennessee  37203