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Phase II Trial of Dasatinib in Patients With Isocitrate Dehydrogenase (IDH)-Mutant Advanced Intrahepatic Cholangiocarcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Bristol-Myers Squibb
TargetCancer Foundation
Information provided by (Responsible Party):
Andrew X. Zhu, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT02428855
First received: April 23, 2015
Last updated: February 16, 2017
Last verified: February 2017
  Purpose
This research study is studying Dasatinib as a possible treatment for cancer of bile ducts.

Condition Intervention Phase
Cholangiocarcinoma
Drug: Dasatinib
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase II Trial of Dasatinib in Patients With Isocitrate Dehydrogenase (IDH)-Mutant Advanced Intrahepatic Cholangiocarcinoma

Resource links provided by NLM:


Further study details as provided by Andrew X. Zhu, MD, Massachusetts General Hospital:

Primary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: 8 Weeks ]
    RECIST Criteria


Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Baseline, 2 Years ]
  • Overall Survival [ Time Frame: Baseline, 2 Years ]
  • Number of Participants with Adverse Events [ Time Frame: 8 Weeks ]
  • Biologic correlative studies of target inhibition [ Time Frame: 2 Years ]
    Patients will have mandatory core tumor biopsies at baseline, 8 weeks following dasatinib treatment and at the time of progression for those who had either SD or responses for more than 4 months. Tumor biopsies will be tested for changes in phospho-paxillin (Src kinase target), activated beta-catenin, Ki-67 (proliferation) and cleaved-caspase 3 (cell death).


Enrollment: 8
Actual Study Start Date: April 2015
Estimated Study Completion Date: September 2022
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dasatinib

Patients with advanced intrahepatic cholangiocarcinoma who have either IDH1 or IDH2 mutations and have received at least one prior platinum containing regimen

  • Dasatinib, oral, daily, predetermined dosage per cycle
  • Radiologic Response Assessment every 2 cycles
Drug: Dasatinib
Other Name: SPRYCEL ™

Detailed Description:

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The standard treatment for metastatic cholangiocarcinoma is combination chemotherapy with gemcitabine and cisplatin. The FDA (the U.S. Food and Drug Administration) has not approved dasatinib for your specific disease (Cholangiocarcinoma) but it has been approved for other uses (Chronic Myeloid Leukemia)

  Eligibility

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

Inclusion Criteria:

  • Participants must meet the following criteria on screening examination to be eligible to participate in the study:
  • Participants must have unresectable or metastatic histologically confirmed intrahepatic cholangiocarcinoma
  • Patients must have either IDH1 or IDH2 mutations (any known mutations) based on the SNaPshot platform or other molecular testing platform from either archived tissue or fresh biopsy (tested in CLIA-certified lab)
  • Patients with other biliary tract cancers (extrahepatic or gallbladder cancers) with IDH1 or IDH2 mutations are allowed
  • Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥10 mm with spiral CT scan. See section 10 for the evaluation of measureable disease.
  • Participants must have received at least one prior platinum-based regimen for advanced cholangiocarcinoma and had progressive disease or become intolerable to the regimen
  • Age ≥18 years.
  • Life expectancy of ≥3 months.
  • ECOG performance status 0 or 1 (see Appendix A).
  • Participants must have adequate organ and marrow function as defined below:

    • Absolute neutrophil count ≥ 1,200/mcL
    • Platelets ≥75,000/mcL
    • Hemoglobin ≥9 g/dL
    • Total bilirubin ≤ 2.5 x the upper limit of normal
    • AST (SGOT)/ALT (SGPT) ≤ 5 X institutional upper limit of normal
    • PT/PTT ≤ 1.5 x ULN
    • Creatinine ≤ 1.5 or GFR ≥ 60 mL/min/1.73m2
    • Serum Albumin ≥2.8 g/dl
  • Prior chemoembolization, radiofrequency ablation, or radiation to the liver is allowed as long as the patient has measurable disease outside of the treated area or measurable progression at the site of the treated area
  • Ability to understand and the willingness to sign a written informed consent document.
  • Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (eg, male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s).
  • Women of childbearing potential must have a negative pregnancy test at screening. Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Postmenopause is defined as amenorrhea ≥ 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason.

Exclusion Criteria:

  • Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
  • Prior treatment with dasatinib
  • Periampullary tumors
  • Chemotherapy, within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin) or those who have not recovered to less than or equal to grade 1 from adverse events due to agents administered more than 4 weeks earlier.
  • The subject has received radiation therapy:

    • to bone or brain metastasis within 14 days of the first dose of study treatment
    • to any other site(s) within 28 days of the first dose of study treatment
  • The subject has active brain metastases or epidural disease (Note: Subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. (Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility.)
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

    • Cardiovascular disorders including

      • Congestive heart failure (CHF): New York Heart Association (NYHA) Class III (moderate) or Class IV (severe) at the time of screening
      • Concurrent uncontrolled hypertension defined as sustained BP > 140 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
      • Diagnosed or suspected congenital long QT syndrome
      • Any of the following within 6 months before the first dose of study treatment:

        • Unstable angina pectoris
        • Clinically-significant cardiac arrhythmias
        • Stroke (including TIA, or other ischemic event)
        • Myocardial infarction
        • Thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter (e.g. vena cava filter) are not eligible for this study)
        • Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
        • Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec), may use either the Fridericia and Bazett's correction
        • Hypokalemia or hypomagnesemia that is not corrected prior to dasatinib administration
        • Patients should not be taking drugs that are generally accepted to have a risk of causing Torsades de Pointes. The following must be discontinued at least 7 days prior to starting dasatinib to be eligible:quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide,dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine,levomethadyl, pentamidine, sparfloxacin, lidoflazine
    • Other clinically significant disorders such as:

      • active infection requiring systemic treatment within 28 days before the first dose of study treatment
      • serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
    • Patients with known moderate/severe pleural effusions that are unrelated to malignancy or established diagnosis of pulmonary arterial hypertension
  • Concurrent malignancy (other than adequately treated non-melanoma skin cancer, superficial transitional cell carcinoma of the bladder, and cervical carcinoma in situ) diagnosed within the past 3 years or any currently active malignancy
  • Psychiatric illness/social situations that would limit compliance with study requirements.
  • The subject has received any other type of investigational agent within 28 days before the first dose of study treatment.
  • The subject is unable to swallow tablets
  • Individuals who are known to be HIV-positive are excluded from this study.
  • Pregnant women are excluded from this study due to the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with dasatinib, breastfeeding should be discontinued if the mother is treated with dasatinib. These potential risks may also apply to other agents used in this study.
  • Subjects may not be receiving any other study agents concurrently while on this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02428855

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Massachusetts General Hospital
Bristol-Myers Squibb
TargetCancer Foundation
Investigators
Principal Investigator: Andrew X. Zhu, MD, PhD Massachusetts General Hospital
  More Information

Responsible Party: Andrew X. Zhu, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02428855     History of Changes
Other Study ID Numbers: 15-007
Study First Received: April 23, 2015
Last Updated: February 16, 2017

Keywords provided by Andrew X. Zhu, MD, Massachusetts General Hospital:
Cholangiocarcinoma

Additional relevant MeSH terms:
Cholangiocarcinoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 25, 2017