Clinical Trial: Nilotinib With Radiation for High Risk Chordoma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase I Study of Nilotinib Given With Radiation For Patients With High Risk Chordoma

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.


Detailed Summary:

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.


Sponsor: Massachusetts General Hospital

Current Primary Outcome: To determine the dose limiting toxicities (DLTs) for participants when treated above the maximum tolerated dose (MTD). [ Time Frame: 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.


Original Primary Outcome: To determine Maximum Tolerated Dose (MTD) of nilotinib(and/or recommended phase 2 dose RP2D) and DLTs of nilotinib when combined with radiation therapy for patients with high risk chordoma. [ Time Frame: 2 years ]

MTD is determined by identifying a dose cohort demonstrating > or = 30% rate of DLTs. A DLT will be defined as any of the following events occurring during days 1-56 of study according to CTCAE version 4.0:

  • 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.


Current Secondary Outcome:

  • Number of Participants with Adverse Events [ Time Frame: 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.

  • Survival [ Time Frame: 2 years ]
    To obtain preliminary data regarding local control, distant control, disease-free survival, and overall survival with this regimen
  • PDGFR signaling [ Time Frame: 2 years ]
    To determine if nilotinib decreases PDGFR signaling in chordoma tumor samples in treated patients


Original Secondary Outcome:

  • Feasibility and Safety [ Time Frame: 2 years ]

    Adverse event profile, as determined by CTC AE version 4.0, will be determined for patients treated with nilotinib and radiation therapy.

    Safety 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 safety 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.

  • Survival [ Time Frame: 2 years ]
    To obtain preliminary data regarding local control, distant control, disease-free survival, and overall survival with this regimen
  • PDGFR signaling [ Time Frame: 2 years ]
    To determine if nilotinib decreases PDGFR signaling in chordoma tumor samples in treated patients


Information By: Massachusetts General Hospital

Dates:
Date Received: July 28, 2011
Date Started: August 2011
Date Completion: December 2017
Last Updated: February 22, 2017
Last Verified: February 2017