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A Phase I Study of NK012 in Combination With Carboplatin in Patients With Advanced Solid Tumors Followed by a Dose Expansion Phase in Patients With Triple Negative Metastatic Breast Cancer

Phase 1
18 Years
Not Enrolling
Advanced Solid Tumors, Metastatic Triple Negative Breast Cancer

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Trial Information

A Phase I Study of NK012 in Combination With Carboplatin in Patients With Advanced Solid Tumors Followed by a Dose Expansion Phase in Patients With Triple Negative Metastatic Breast Cancer

NK012 will be administered as a 30 minute IV infusion, followed by a 30 minute carboplatin
IV infusion. Both drugs will be administered once every 28 days. 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, a dose expansion cohort of patients with metastatic
triple negative breast cancer will be treated at the determined MTD.

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 the MTD/RD only:

1. Patients must have triple-negative breast cancer with locally advanced disease
for which there is no surgical option, or stage IV disease. Triple-negative
breast cancer is defined as HER2-negative, ER-negative, and PR-negative as

For HER2- negative (must meet one of the following 3):

( i) FISH negative (ratio <2.2); or ( ii) IHC 0 or 1+; or (iii) IHC 2+ or 3+
and FISH negative (ratio <2.2) For ER negative and PR negative: ≤ 10% tumor
staining by IHC

2. No less than one and no more than two prior chemotherapy regimens for advanced
or metastatic breast cancer.

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

3. Patients 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 or 1.

7. Life expectancy of at least 12 weeks.

8. Patients are at least 18 years of age.

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

10. AST and ALT ≤ 3.0 x ULN (5X 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 > 1.5x 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

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 another 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 child-bearing
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,
or platinum-containing compounds.

9. Prior treatment with irinotecan.

10. Prior treatment with more than 6 cycles of platinum drugs.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, 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:


Principal Investigator

Howard Burris, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sarah Cannon Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

July 2010

Completion Date:

March 2013

Related Keywords:

  • Advanced Solid Tumors
  • Metastatic Triple Negative Breast Cancer
  • solid tumors
  • breast cancer
  • triple negative breast cancer
  • HER2 negative
  • ER negative
  • PR negative
  • Breast Neoplasms
  • Neoplasms



Sarah Cannon Research InstituteNashville, Tennessee  37203