Nilotinib With Radiation for High Risk Chordoma

Sponsor
Massachusetts General Hospital (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01407198
Collaborator
(none)
29
Enrollment
1
Location
1
Arm
172
Duration (Months)
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study drug, Nilotinib, is believed to slow down tumor growth by regulating a gene involved in cellular growth of chordoma cells. During this research study, subjects will also receive radiation therapy which is considered a standard treatment for advanced chordomas. It is hoped by adding nilotinib, the benefits of radiation therapy can be enhanced without adding significant toxicities.

The purpose of this research study is to determine the safety of nilotinib when used in combination with radiation therapy, and the highest dose of nilotinib that can be given safely with radiation therapy.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Detailed Description

Nilotinib will be taken orally daily in two cycles of 28 days each. Two weeks after taking nilotinib, subjects will begin radiation therapy. Radiation therapy will continue every weekday until Day 56 of the study. If it is determined that the subject's tumor cannot be removed by surgery, an additional 3 weeks of radiation therapy will be applied after Day 56 of the study.

During study visits subjects will have physical exams, routine blood tests, urine and blood clotting tests, and EKGs. Subjects will also have tumor assessment by chest CT and MRI or CT of the tumor at screening, on approximately Day 56 of the study, then every 6 months for one year and then annually thereafter if ther is no disease progression.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
29 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I Study of Nilotinib Given With Radiation For Patients With High Risk Chordoma
Study Start Date :
Aug 1, 2011
Actual Primary Completion Date :
Feb 1, 2016
Anticipated Study Completion Date :
Dec 1, 2025

Arms and Interventions

ArmIntervention/Treatment
Experimental: Nilotinib/XRT

Nilotinib is administered 400mg PO BID for 2 weeks and then administered concurrently with daily radiation therapy until completion of radiation therapy. Participants can then undergo surgery if clinically possible. After either surgery or definitive radiation, participants have the option to continue on nilotinib therapy.

Drug: Nilotinib
Orally, daily 200 - 400 mg BID
Other Names:
  • AMN 107
  • Tasigna
  • Radiation: Radiation therapy
    External beam radiation will be delivered at 1.8 Gy per day, 5 days per week (excluding holidays)for a total of 28 fractions over a 6 weeks period.
    Other Names:
  • External beam radiation
  • Outcome Measures

    Primary Outcome Measures

    1. To determine the dose limiting toxicities (DLTs) for participants when treated above the maximum tolerated dose (MTD). [2 years]

      A DLT will be defined as any of the following events occurring during days 1-56 of study according to CTCAE version 4.0. MTD is then determined by identifying a dose cohort demonstrating > or = 30% rate of DLTs, which are defined as: Any Grade ≥ 3 nonhematologic toxicity except alopecia, nausea, or vomiting not otherwise controlled by maximual supportive care. Grade 4 neutropenia (ANC < 500/µL) lasting > 5 days, Grade 3 thrombocytopenia lasting > 7 days, or Grade 4 thrombocytopenia Failure to resume treatment delays within a defined period of time.

    Secondary Outcome Measures

    1. Number of Participants with Adverse Events [2 years]

      Adverse event profile, as determined by CTC AE version 4.0, will be determined for patients treated with nilotinib and radiation therapy. Adverse events analyses will include: Detailed examination of adverse events Laboratory test results Vital signs or other physical findings Frequency and extent of dose modification The assessment of adverse events will be based mainly on the frequency of adverse events, particularly adverse events leading to discontinuation of treatment and on the number of significant laboratory abnormalities.

    2. Survival [2 years]

      To obtain preliminary data regarding local control, distant control, disease-free survival, and overall survival with this regimen

    3. PDGFR signaling [2 years]

      To determine if nilotinib decreases PDGFR signaling in chordoma tumor samples in treated patients

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically confirmed chordoma

    • Considered to have high risk disease

    • Measurable disease

    • Life expectancy > 3 months

    • Adequate organ function

    • Able to swallow oral capsules

    Exclusion Criteria:
    • Previous treatment with any other tyrosine kinase inhibitor

    • Previous treatment with radiotherapy to the primary or recurrent chordomas

    • Impaired cardiac function

    • Currently receiving treatment with strong CYP3A4 inhibitors

    • Requires anticoagulation with coumadin

    • Impaired GI function or GI disease that may significantly alter the absorption of study drug

    • Acute or chronic pancreatic disease

    • Known cytopathologically confirmed CNS infiltration

    • Another primary malignant disease which requires systemic treatment

    • Acute or chronic liver disease or severe renal disease considered unrelated to the cancer

    • History of significant congenital or acquired bleeding disorder unrelated to cancer

    • Major surgery within 4 weeks prior to Day 1 of the study or who have not recovered from prior surgery

    • Treatment with other investigational agents within 30 days of Day 1

    • History of non-compliance to medical regimens

    • Pregnant or breast-feeding

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Massachusetts General HospitalBostonMassachusettsUnited States02114

    Sponsors and Collaborators

    • Massachusetts General Hospital

    Investigators

    • Principal Investigator: Edwin Choy, MD, PhD, Massachusetts General Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Edwin Choy, MD, Instructor, Massachusetts General Hospital
    ClinicalTrials.gov Identifier:
    NCT01407198
    Other Study ID Numbers:
    • 11-072
    First Posted:
    Aug 2, 2011
    Last Update Posted:
    Oct 29, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Edwin Choy, MD, Instructor, Massachusetts General Hospital
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 29, 2021