BNCT and IG-IMRT for Recurrent Head and Neck Cancer

A Phase I/II Trial of Boron Neutron Capture Therapy (BNCT) Combined With Image-guided Intensity Modulated Radiotherapy (IG-IMRT) for Locally Recurrent Head and Neck Cancer

This is a boron neutron capture therapy (BNCT) combined with image-guided intensity modulation radiotherapy (IG-IMRT) for patients with previously irradiated and locally recurrent head and neck cancer. The primary end points are treatment toxicities and response rate. The secondary endpoints are time to tumor progression, progression-free survival, overall survival and change quality of life.

Head and neck(H & N) carcinomas that recur locally after conventional irradiation pose a therapeutic challenge. Boron neutron capture therapy (BNCT) is based on the nuclear capture reaction that occurs when non-radioactive boron is irradiated with neutrons of thermal energy to yield high energy alpha particles and recoiling lithium nuclei. The effect of alpha and 7Li is primarily limited to boron-containing cells. Preferential uptake of boron into cancerous tissue is achieved using boron carriers such as a derivative of phenylalanine, boronophenylalanine (BPA). After administration of BPA by intravenous infusion, the tumor site is irradiated with neutrons, the source of which is currently a nuclear reactor, like the Tsing Hua Open-Pool Reactor (THOR), a 2MW research reactor at National Tsing Hua University (NTHU) in Taiwan. Since it is a target radiotherapy, low complication rate after BNCT can be obtained. However, further local recurrence after BNCT for recurrent H & N cancer was reported in several publications.

Image-guided radiation therapy (IGRT) is the process of frequent two and three-dimensional imaging, during a course of radiation treatment, used to direct radiation therapy utilizing the imaging coordinates of the approved radiation treatment plan. IGRT such as Cone-Beam CT (CBCT) using an On-Board Imager (OBI) enhance delivery and further improve outcomes as the treatments create a higher level of precision. By combining BNCT and IG-IMRT, we expect to procure high control rate of recurrent H & N cancer with acceptable toxicity. This study will be the first BNCT plus IG-IMRT trial to treat head and neck cancer in Taiwan.

Study Overview

• Status: Unknown
• Conditions: Recurrence; Head and Neck Cancer
• Intervention / Treatment: Radiation: BNCT + IG-IMRT

• Study Type: Interventional
• Enrollment (Anticipated): 28
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 112
    • Recruiting
    • Taipei Veterans General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• For BNCT:

  1. Patients with locoregionally recurrent, histologically proved malignancy of the head and neck, including primary sites of oral cavity, oropharynx, hypopharynx, nasopharynx, paranasal sinus, nasal cavity, the orbit, thyroid and larynx. Pathology types like melanoma and sarcoma are also included.
  2. Prior conventional radiotherapy administered has been given for the disease (except melanoma).
  3. Bi-dimensionally measurable disease by MRI and/or CT scan and ≦ 12 cm in largest dimension.
  4. Age greater than 18 years and < 80 years, ECOG performance status ≦ 2
  5. WBC > 2.5 x109/L, neutrophil count >1.0 x109/L, platelet count >75x109/L, serum creatinine <1.25xULN.
  6. Informed consent signed.
  7. Tumor/normal tissue (T/N) ratio≧2.5 by BPA-PET scan.

• For IG-IMRT:

  1. ECOG performance status ≦ 2
  2. No evidence of disease progression by physical examination or CT simulation.
  3. Nutrition support (feeding tube and/or IV fluid) already given for dysphagia, if present.
  4. Severity of mucositis and radiation dermatitis improved or downgrading, compared with those found in the 2nd or 3rd week after BNCT.

Exclusion Criteria:

• For BNCT:

  1. Lymphoma or other tumor type that is expected to respond to cancer chemotherapy or to a dose of conventional radiation therapy that can be safely given.
  2. Patients who have an effective standard treatment option available.
  3. Distant metastasis outside of the head and neck region.
  4. Expecting life less than 3 months.
  5. A time interval less than 6 months from previous radiation therapy.
  6. Prior high-dose radiotherapy (Biological Effective Dose> 70 Gy/35 fractions) has been given for the present recurrent site within one year.
  7. Patients who had radiation myelitis or radiation necrosis of the brain/brain stem
  8. Time to recurrence from completion of prior surgery less than 6 months.
  9. Concurrent systemic cancer treatment including chemotherapy or target therapy (including cetuximab or EGFR oral tyrosine kinase inhibitor).
  10. Severe congestive heart failure or renal failure.
  11. Pregnancy
  12. Restless patients who were unable to lie or sit in a cast for 30-60 min.
  13. A cardiac pace-maker or an unremovable metal implant present in the head and neck region that will interfere with MRI-based dose-planning or tumor response evaluation.

• For IG-IMRT:

  1. Any grade IV toxicity after BNCT.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BNCT+ IG-IMRT; single arm	Radiation: BNCT + IG-IMRT; Single faction of BNCT (20 Gy) plus IG-IMRT (40 Gy/20 fractions)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
treatment toxicities	To evaluate both acute and late toxicities after combined BNCT and IG-IMRT	two years after combined treatment
response rate	including complete and partial response rate after BNCT+IG-IMRT	Three months after combined treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to tumor progression	defined from the date of BNCT to the date of tumor progression by clinical evaluation.	two years
Progression-free survival	calculated from the date of BNCT to the date of cancer progression either locally or distally or to death	two years

Collaborators and Investigators

• Sponsor: Taipei Veterans General Hospital, Taiwan
• Collaborators: National Tsing Hua University,Taiwan

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Anticipated): November 1, 2016
• Study Completion (Anticipated): November 1, 2018

Study Registration Dates

• First Submitted: November 11, 2013
• First Submitted That Met QC Criteria: December 3, 2013
• First Posted (Estimate): December 9, 2013

Study Record Updates

• Last Update Posted (Estimate): December 9, 2013
• Last Update Submitted That Met QC Criteria: December 3, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Boron Neutron Capture Therapy; Image-guided intensity modulation radiotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Site; Disease Attributes; Head and Neck Neoplasms; Recurrence
• Other Study ID Numbers: 2012-06-016A