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Dose-Escalation Study of Oral CX-4945
This study is currently recruiting participants.
Verified by Cylene Pharmaceuticals, April 2009
First Received: April 29, 2009   Last Updated: April 30, 2009   History of Changes
Sponsored by: Cylene Pharmaceuticals
Information provided by: Cylene Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00891280
  Purpose

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.


Condition Intervention Phase
Advanced Solid Tumors
Breast Cancer
Inflammatory Breast Cancer
Castleman's Disease
Multiple Myeloma
Drug: CX-4945 oral formulation
Phase I

Genetics Home Reference related topics: aceruloplasminemia breast cancer hemophilia
MedlinePlus related topics: Breast Cancer Cancer Multiple Myeloma
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study
Official Title: 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

Further study details as provided by Cylene Pharmaceuticals:

Primary Outcome Measures:
  • Safety (Dose limiting toxicities, maximum tolerated dose) [ Time Frame: One year (Assessed at Cycle 1) ] [ Designated as safety issue: Yes ]
  • Drug-related adverse events [ Time Frame: One Year (Asessed from first administration of study drug through 30 days after the last dose) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetic and pharmacodynamic assessments [ Time Frame: One Year (Assessed during Cycle 1) ] [ Designated as safety issue: No ]
  • Observe evidence of antitumor activity [ Time Frame: One Year (Assessed after every two cycles) ] [ Designated as safety issue: No ]
  • Establish the recommended Phase 2 dose [ Time Frame: One Year (Study completion) ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: February 2009
Estimated Study Completion Date: March 2010
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: CX-4945 oral formulation
    CX-4945 Capsules, Oral, Dose escalation study, Dose schedule: twice daily for 21 consecutive days every 28 days.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00891280

Locations
United States, Arizona
Mayo Clinic Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Clinical Trials Office Mayo Clinic Cancer Center     507-538-7623        
Principal Investigator: Donald Northfelt, MD            
United States, Colorado
Front Range Cancer Specialists Recruiting
Fort Collins, Colorado, United States, 80528
Contact: J. Shelby, RN     970-212-7609        
Principal Investigator: Robert F Marschke, MD            
Sponsors and Collaborators
Cylene Pharmaceuticals
Investigators
Study Director: Study Director Cylene Pharmaceuticals
  More Information

No publications provided

Responsible Party: Cylene Pharmaceuticals Inc ( Study Director )
Study ID Numbers: C4-08-001
Study First Received: April 29, 2009
Last Updated: April 30, 2009
ClinicalTrials.gov Identifier: NCT00891280     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Cylene Pharmaceuticals:
Inflammatory breast cancer
Castleman's Disease
Multiple Myeloma
Breast cancer
Solid tumors
CK2 inhibitor

Study placed in the following topic categories:
Immunoproliferative Disorders
Skin Diseases
Hematologic Diseases
Blood Protein Disorders
Giant Lymph Node Hyperplasia
Blood Coagulation Disorders
Vascular Diseases
Breast Neoplasms
Paraproteinemias
Hemostatic Disorders
Multiple Myeloma
Lymphatic Diseases
Hyperplasia
Hemorrhagic Disorders
Inflammatory Breast Cancer
Castleman's Disease
Lymphoproliferative Disorders
Breast Diseases
Neoplasms, Plasma Cell

Additional relevant MeSH terms:
Immunoproliferative Disorders
Neoplasms by Histologic Type
Skin Diseases
Immune System Diseases
Hematologic Diseases
Blood Protein Disorders
Giant Lymph Node Hyperplasia
Vascular Diseases
Breast Neoplasms
Paraproteinemias
Hemostatic Disorders
Multiple Myeloma
Lymphatic Diseases
Neoplasms
Hemorrhagic Disorders
Neoplasms by Site
Cardiovascular Diseases
Lymphoproliferative Disorders
Breast Diseases
Neoplasms, Plasma Cell

ClinicalTrials.gov processed this record on May 07, 2009