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Trial record 5 of 148 for:    cholangiocarcinoma | Recruiting, Not yet recruiting, Available Studies

Study of CX-4945 in Combination With Gemcitabine and Cisplatin for Frontline Treatment of Cholangiocarcinoma

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ClinicalTrials.gov Identifier: NCT02128282
Recruitment Status : Recruiting
First Posted : May 1, 2014
Last Update Posted : October 23, 2017
Sponsor:
Information provided by (Responsible Party):
Senhwa Biosciences, Inc.

Brief Summary:
This study considers the safety and tolerability of increasing doses of CX-4945 in combination with gemcitabine plus cisplatin to determine the maximum tolerated dose (MTD), followed by a randomized study that compares antitumor activity in cholangiocarcinoma patients receiving the standard of care gemcitabine plus cisplatin versus CX-4945 at the combination MTD with gemcitabine plus cisplatin.

Condition or disease Intervention/treatment Phase
Cholangiocarcinoma Drug: CX-4945 Drug: Cisplatin Drug: Gemcitabine Phase 1 Phase 2

Detailed Description:

Protein kinase CK2 is a constitutively active serine/threonine kinase with a long history as a pro-survival, anti-apoptotic kinase. Given the wide spread overexpression of CK2 in multiple cancers and its role in multiple non-oncogenic processes required to sustain the cancer phenotype, a selective inhibitor of CK2 is an attractive targeted approach to treating cancer.

CX-4945 is a tetracyclic, small molecule carboxylate acid salt that exhibits potent and highly selective inhibition of CK2. Protein kinase CK2 is also known to play an important role in the DNA damage repair mechanisms of cancer cells, and this study of CX-4945 in combination with gemcitabine plus cisplatin will determine if inhibition of CK2, in conjunction with the use of chemotherapy drugs, will result in improved clinical outcomes for patients with non-resectable cholangiocarcinoma.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 209 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of CX-4945 in Combination With Gemcitabine and Cisplatin in the Frontline Treatment of Patients With Cholangiocarcinoma
Study Start Date : June 2014
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Experimental: CX-4945 and cisplatin plus gemcitabine

CX-4945 capsules at the combination MTD on Days 0, 1 and 2, and Days 7, 8 and 9.

PLUS Cisplatin 25 mg/m.sq. by IV infusion on Days 1 and 8. PLUS Gemcitabine 1,000 mg/m.sq. by IV infusion on Days 1 and 8. On a 21 day cycle.

Drug: CX-4945
Capsules administered twice daily on Days 0, 1 and 2, and Days 7, 8 and 9 of each 21 day cycle.

Drug: Cisplatin
25 mg/m.sq. administered by IV infusion on Days 1 and 8 of a 21 day cycle.
Other Name: Platinol

Drug: Gemcitabine
1,000 mg/m.sq. administered by IV infusion on Days 1 and 8 of a 21 day cycle.
Other Name: Gemzar

Active Comparator: Cisplatin plus Gemcitabine
Cisplatin 25 mg/m.sq. by IV infusion on Days 1 and 8. PLUS Gemcitabine 1,000 mg/m.sq. by IV infusion on Days 1 and 8. On a 21 day cycle.
Drug: Cisplatin
25 mg/m.sq. administered by IV infusion on Days 1 and 8 of a 21 day cycle.
Other Name: Platinol

Drug: Gemcitabine
1,000 mg/m.sq. administered by IV infusion on Days 1 and 8 of a 21 day cycle.
Other Name: Gemzar




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of CX-4945 when used in combination with gemcitabine plus cisplatin [ Time Frame: Up to twenty-one (21) days ]
    The Maximum Tolerated Dose of CX-4945 will be determined from safety observations during the first cycle, as the CX-4945 dose is escalated in cohorts of three patients in combination with standard gemcitabine plus cisplatin.

  2. Comparison of the Progression-free survival (PFS) between the test and the control arms using Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 [ Time Frame: From date of randomization to date of progression or death from any cause up to 52 weeks. ]
    Tumor measurements will be compared to baseline every six weeks, and the PFS will be determined using RECIST v. 1.1.


Secondary Outcome Measures :
  1. Comparison of the Overall-response rate (ORR) between the test and the control arms using Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 [ Time Frame: From date of randomization to date of progression or death from any cause up to 52 weeks. ]
    Tumor measurements will be compared to baseline, and the ORR will be determined using RECIST v. 1.1



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Presence of an unresectable liver mass consistent with cholangiocarcinoma, for which treatment with gemcitabine plus cisplatin is intended.
  • For patients enrolled in the Dose Escalation Phase, one or more tumors measurable on radiograph or CT scan, or evaluable disease defined as non-measurable lesions per RECIST v. 1.1 (e.g., malignant ascites). All patients enrolled to the Randomized Study Phase must have measurable disease only.
  • Laboratory data as specified below:

    • Hematology: Absolute neutrophil count (ANC) >1,500 cells/mm3, platelet count >100,000 cells/ mm.cu. and hemoglobin > 9 g/dL
    • Hepatic: bilirubin <1.5 X Upper Limit of Normal (ULN); alkaline phosphatase (ALP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5.0 X ULN
    • Renal: serum creatinine within normal limits (WNL), defined as within 25% of the institution's stated reference range, or a calculated creatinine clearance >45 mL/min/1.73 m. sq. for patients with abnormal, increased, creatinine levels.
    • Coagulation: International Normalized Ratio (INR) < 1.5 times normal, activated Partial Thromboplastin Time (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.
  • Estimated life expectancy of at least 3 months.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 1.

Exclusion Criteria:

  • A history of prior systemic treatment with gemcitabine or cisplatin. At least six months must have elapsed if gemcitabine or cisplatin was administered in an adjuvant treatment setting.
  • Seizure disorders requiring anticonvulsant therapy.
  • Known brain metastases (unless previously treated and well controlled for a period of at least 3 months).
  • Major surgery other than diagnostic surgery, within 4 weeks prior to the first dose of test drug, minor surgery including diagnostic surgery within 2 weeks (14 days) excluding central IV port placements and needle aspirate/core biopsies. Radio frequency ablation or transcatheter arterial chemoembolization within 6 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 another malignancy within 3 years of the baseline visit. (Patients with cutaneous carcinomas or in-situ carcinomas will be considered for study entry on a case-by-case basis).
  • Concurrent severe or uncontrolled medical disease (i.e., systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure).
  • Active symptomatic fungal, bacterial and/or viral infection including active HIV or viral (A, B or C) hepatitis.
  • Difficulty with swallowing or an active malabsorption syndrome.
  • Chronic diarrhea (excess of 2-3 stools/day above normal frequency).
  • 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 of CX-4945.
  • Concomitant use either of warfarin and/or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02128282


Locations
United States, Arizona
Mayo Clinic Recruiting
Scottsdale, Arizona, United States, 85259-5499
Contact: Mayo Clinic Clinical Trials Office    855-776-0015      
Principal Investigator: Mitesh Borad, M.D.         
United States, Colorado
University of Colorado- Denver Recruiting
Aurora, Colorado, United States, 80045
Contact: Amy Szilard    720-848-0702    Amy.Szilard@ucdenver.edu   
Principal Investigator: Sarah (Lindsey) Davis, MD         
United States, Florida
Mayo Clinic Recruiting
Jacksonville, Florida, United States, 32224
Contact: Mayo Clinic Clinical Trials Office    855-776-0015      
Principal Investigator: Kabir Mody, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mayo Clinic Clinical Trials Office    855-776-0015      
Principal Investigator: Joleen Hubbard, MD         
United States, Texas
Texas Oncology - Baylor Charles A. Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: Tammy Carmical, RN    214-370-1937    tammy.carmical@usoncology.com   
Principal Investigator: Carlos Becerra, M.D.         
Texas Oncology-Tyler Recruiting
Tyler, Texas, United States, 75702
Contact: Karen Poe, RN    903-579-9869    karen.poe@usoncology.com   
Principal Investigator: Donald A Richards, M.D.         
Korea, Republic of
Samsung Medical Center Recruiting
Seoul, Korea, Republic of
Contact: Eunyou Lee    82-2-3410-0955    ley0709@samsung.com   
Principal Investigator: Joon Oh Park, MD         
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of
Contact: Myoungsun Choi    82-2-2072-7612    iamyou3@hanmail.net   
Principal Investigator: Do-Youn Oh, MD         
Severance Hospital, Yonsei University Health System Recruiting
Seoul, Korea, Republic of
Contact: So Young Hwang    82-2-2228-8180    syhwang@yuhs.ac   
Principal Investigator: Sun Young Rha, MD         
Taiwan
China Medical University Hospital Recruiting
Taichung City, Taiwan
Contact: Pei-Chen Hsu    +886-4-2205-2121    peggyshiu0807@gmail.com   
Principal Investigator: Li-Yuan Bai, M.D.         
Sponsors and Collaborators
Senhwa Biosciences, Inc.
Investigators
Principal Investigator: Mitesh Borad, M.D. Mayo Clinic

Responsible Party: Senhwa Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT02128282     History of Changes
Other Study ID Numbers: S4-13-001
First Posted: May 1, 2014    Key Record Dates
Last Update Posted: October 23, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Senhwa Biosciences, Inc.:
Cholangiocarcinoma
Bile duct cancer
Biliary tract cancer

Additional relevant MeSH terms:
Cholangiocarcinoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Cisplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs