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Dose-escalation Study of Oral CX-4945

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ClinicalTrials.gov Identifier: NCT00891280
Recruitment Status : Unknown
Verified June 2011 by Cylene Pharmaceuticals.
Recruitment status was:  Recruiting
First Posted : May 1, 2009
Last Update Posted : June 15, 2011
Sponsor:
Information provided by:
Cylene Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE April 29, 2009
First Posted Date  ICMJE May 1, 2009
Last Update Posted Date June 15, 2011
Study Start Date  ICMJE February 2009
Estimated Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 30, 2009)
  • Safety (Dose limiting toxicities, maximum tolerated dose) [ Time Frame: One year (Assessed at Cycle 1) ]
  • Drug-related adverse events [ Time Frame: One Year (Asessed from first administration of study drug through 30 days after the last dose) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2009)
  • Pharmacokinetic and pharmacodynamic assessments [ Time Frame: One Year (Assessed during Cycle 1) ]
  • Observe evidence of antitumor activity [ Time Frame: One Year (Assessed after every two cycles) ]
  • Establish the recommended Phase 2 dose [ Time Frame: One Year (Study completion) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-escalation Study of Oral CX-4945
Official Title  ICMJE A Phase 1, Multi-Center, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of CX-4945 Administered Orally to Patients With Advanced Solid Tumors, Castleman's Disease or Multiple Myeloma
Brief Summary This Phase 1 study of oral CX-4945 is designed to test the safety, tolerability and highest safe dose level of this CK2 inhibitor in patients with advanced solid tumor cancers, Castleman's Disease or Multiple Myeloma.
Detailed Description Elevated CK2 activity has been associated with malignant transformation and aggressive tumor growth and overexpression of CK2 has been documented in multiple types of cancer. CK2 has emerged as a potential anticancer target and inhibition of CK2 represents a potential therapeutic strategy to target a specific molecular defect perpetuating many cancers. CX-4945 has demonstrated potent inhibition of CK2 enzymatic activity. This study will evaluate the safety, pharmacokinetics (PK), and pharmacodynamic (PD) effects of CX-4945 administered to patients with malignancies or lymphoproliferative disorders known to overexpress CK2 including advanced solid tumors, Multiple Myeloma and Castleman's Disease.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumors
  • Breast Cancer
  • Inflammatory Breast Cancer
  • Castleman's Disease
  • Multiple Myeloma
Intervention  ICMJE Drug: CX-4945 oral formulation
CX-4945 Capsules, Oral, Dose escalation study, Dose schedule: twice daily or four times daily for 21 consecutive days every 28 days.
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: February 18, 2011)
55
Original Estimated Enrollment  ICMJE
 (submitted: April 30, 2009)
40
Estimated Study Completion Date  ICMJE December 2011
Estimated Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed malignancy or lymphoproliferative disorder known to over express CK2 which has failed standard therapies (surgery, radiotherapy, endocrine therapy, chemotherapy) or for which effective therapy is not available, including the following types: (examples)

    • Lung cancer
    • Renal cell cancer
    • Breast cancer
    • Inflammatory breast cancer
    • Head and neck cancer - squamous cell
    • Prostate cancer
    • Colorectal cancer
    • Castleman's disease (multi-centric disease)
    • Multiple myeloma (Eligible patients must have quantifiable M-protein levels present in serum and/or urine)
  • At least 18 years of age.
  • One or more tumors measurable on radiograph or CT scan, or evaluable disease defined as non-measurable lesions per RECIST or detection of protein M in serum and/or urine of patients with Multiple Myeloma (serum ≥ 10 gm/L and urine ≥ 200 mg/24 hr).
  • Laboratory data as specified below:
  • Hematology: ANC >1500 cells/mm3, platelet count >100,000 cells/mm3 and Hemoglobin > 9 gm/L
  • Hepatic: bilirubin <1.5 X ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 X ULN. Patients with known liver metastases or liver neoplasms: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5.0 X ULN
  • Renal: serum creatinine within normal limits (WNL), defined as within 10% of the institution's stated reference range, or a calculated creatinine clearance >60 mL/min/1.73 m2 for patients with abnormal, increased, creatinine levels. Patients with Multiple Myeloma (only): serum creatinine ≤ 2.5 the institutional upper limit of the normal range and a calculated creatinine clearance > 40 mL/min/1.73 m2.
  • Coagulation: INR < 1.5 times normal, aPTT < 1.5 times normal. Patients receiving therapeutic doses of anticoagulant therapy may be considered eligible for the trial if INR and aPTT are within the acceptable therapeutic limits for the institution.
  • A negative pregnancy test (if female of childbearing potential).
  • Estimated life expectancy of at least 3 months
  • Karnofsky Performance Status ≥ 70%
  • For men and women of child-producing potential, use of effective contraceptive methods during the study
  • Ability to understand the requirements of the study, provide written informed consent.

Exclusion Criteria:

  • Pregnant or nursing women.
  • Seizure disorders requiring anticonvulsant therapy.
  • Known brain metastases (unless previously treated and well controlled for a period of > or = 3 months).
  • Major surgery, other than diagnostic surgery, within 4 weeks prior to the first dose of test drug.
  • Treatment with radiation therapy or surgery within one month prior to study entry
  • Treatment with chemotherapy or investigational drugs within 21 days prior to the screening visit. Acute toxicities from prior therapy must have resolved to Grade ≤ 1 above baseline.
  • Patients with a history of a second malignancy within 3 years of the baseline visit excluding cutaneous carcinomas and in-situ carcinoma.
  • Concurrent severe or uncontrolled medical disease.
  • Active symptomatic fungal, bacterial and/or viral infection including active HIV or viral hepatitis.
  • Difficulty with swallowing or an active malabsorption syndrome
  • Chronic diarrhea
  • Gastrointestinal diseases including gastritis, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis
  • History of gastric or small bowel surgery involving any extent of gastric or small bowel resection.
  • Clinically significant bleeding event within the last 3 months, unrelated to trauma, or underlying condition that would be expected to result in a bleeding diathesis
  • Patients who have exhibited allergic reactions to a similar structural compound or to a formulation component.
  • Concomitant use of warfarin and HMG-CoA reductase inhibitors (statins)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00891280
Other Study ID Numbers  ICMJE C4-08-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Study Director, Cylene Pharmaceuticals Inc
Study Sponsor  ICMJE Cylene Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director Cylene Pharmaceuticals
PRS Account Cylene Pharmaceuticals
Verification Date June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP