Study of NK012 and Carboplatin in Solid Tumors With Dose Expansion in Triple Negative Breast Cancer

NCT01238952 | Completed Phase 1

• 1 other identifier: A6012121US
• Study Type: interventional
• Target: 4
• 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 carboplatin in patients with advanced solid tumors.

Conditions

Advanced Solid Tumors; Metastatic Triple Negative Breast Cancer

Keywords

solid tumors; breast cancer; triple negative breast cancer; HER2 negative; ER negative; PR negative

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 on average every 2 months until off-study

• Peak Plasma Concentration (Cmax) of NK012 and carboplatin

  15,30,60min,1,6,24,48,50,72hrs,1,2,3,4wk

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

  15,30,60min,1,6,24,48,50,72hrs,1,2,3,4wk

Interventions

NK012 and carboplatin DRUG

NK012 and carboplatin via infusion once every 28 days

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 the MTD/RD only:
• 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 follows:
• 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
• No less than one and no more than two prior chemotherapy regimens for advanced or metastatic breast cancer.
• Patients must have measurable disease by RECIST (version 1.1).
• Patients 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 or 1.
• Life expectancy of at least 12 weeks.
• Patients are at least 18 years of age.
• Adequate bone marrow function defined as ANC ≥ 1500/mm\^3 and platelet count ≥ 100,000/mm\^3.
• AST and ALT ≤ 3.0 x ULN (5X ULN if documented liver metastases) and total bilirubin ≤ 1.5 x ULN.

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 another 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 child-bearing 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, or platinum-containing compounds.
• Prior treatment with irinotecan.
• Prior treatment with more than 6 cycles of platinum drugs.

Sponsors & Collaborators

• Nippon Kayaku Co., Ltd.: lead

Study Sites (1)

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Howard Burris, MD

  SCRI Development Innovations, LLC

  PRINCIPAL INVESTIGATOR

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: July 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: March 1, 2013
• Last Updated: November 13, 2014

Record last verified: 2013-03

Locations

US (1)