Phase I Study of IMRT and Molecular-Image Guided Adaptive Radiation Therapy for Advanced HNSCC

Stage IV Squamous Cell Carcinoma of the Hypopharynx Clinical Trial

Official title:

A Phase I Dose Escalation Trial: Concurrent Intensity-Modulated Radiotherapy (IMRT) and Chemotherapy With Molecular Image-Guided Adaptive Radiation Therapy (IGART) for Advanced Head and Neck Squamous Cell Carcinomas (HNSCC)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01283178
• Other study ID #: MCC 13222
• Secondary ID: NCI-2010-02340P3
• Status: Terminated
• Phase: Phase 1
• First received: January 24, 2011
• Last updated: October 27, 2016
• Start date: July 2011
• Est. completion date: September 2016

Study information

• Verified date: October 2016
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. CT and PET scans and treatment-planning systems may help in planning radiation therapy. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with cisplatin may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of intensity-modulated image guided adaptive radiation therapy when given together with cisplatin in treating patients with locally advanced head and neck squamous cell cancer

Description:

PRIMARY OBJECTIVES:

I. To determine the feasibility of integrating molecular imaging (PET with FLT tracer) into current state-of-the-art image-guided adaptive radiation therapy (IGART) of head and neck cancer.

II. To determine within a predefined range the maximum tolerated radiation dose for concurrent cisplatin and molecular and anatomic image-based IGART of head and neck cancer.

SECONDARY OBJECTIVES I. To compare gross tumor volumes defined by FDG-PET, FLT-PET, CBCT, and regular FBCT before, during, and following completion of chemo-radiation therapy.

II. To evaluate the impact of escalated doses to tumor sub-volumes with high FLT and FDG uptake prior to and during radiation therapy using post-treatment FDG images as an early surrogate for sub-volume-specific local control.

III. To develop a database consisting of all molecular and anatomic images, including daily CBCT data sets, obtained during chemo-radiation therapy to support further research. Potential applications include determination of optimal adaptive re-planning frequency and the benefits of basing IGART on 4D anatomic data sets derived from deformably registering daily CBCT and FBCT data sets.

IV. Determine patient long-term toxicities and survival. V. To evaluate the impact of daily image-guided setup; off-line every other week adaptive re-planning; and molecular-image based targeting on sparing of tissues and organs responsible for late and early treatment sequelae.

OUTLINE: This a dose-escalation study of intensity-modulated radiotherapy.

Patients undergo intensity-modulated image-guided adaptive radiotherapy once daily 5 days a week for 6 weeks. Patients also receive cisplatin IV on days 1 and 22. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 2 and 4 weeks, 2, 3, 4, 5, 6, 9, and 12 months, every 6 months for 2 years, and then annually for 2 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: September 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• Histologic or cytologic confirmation of head and neck malignancy without clinical or radiographic evidence of metastatic disease

• Locally advanced HN SCC, stages III, IV, and bulky (> 27 cm^3 volume) stage II, excluding larynx and nasopharynx, of no more than 150 cm^3 volume base on CT scan

• All patients must be informed of the investigational nature of this study and must give written informed consent in accordance with institutional and federal guidelines

• Candidate for chemotherapy

• Zubrod performance score of 0 or 1

• Absolute granulocyte count (AGC) >= 2000 cells/mm^3

• Platelet count >= 100,000 cells/mm^3

• Hemoglobin > 8.0 g/dl based upon CBC/differential obtained within 2 weeks prior to registration on study

• Serum creatinine =< 1.5 mg/dl or measured or calculated creatinine clearance >= 50 ml/min

• Negative pregnancy test within 2 weeks prior to registration for women of childbearing potential

Exclusion Criteria:

• Prior invasive malignancy except non-melanomatous skin cancers unless patient has been disease free for at least 3 years

• Prior cancer treatment for this cancer, including gross total tumor excision

• Prior radiation treatment to the HN region

• Patients with known syndromes that alter radiosensitivity

• Any medical contraindications for chemotherapy

• Pregnant or lactating women

• Women (of childbearing potential) and men who are sexually active and are not willing/able to use a medically acceptable form of contraception throughout the treatment and 60 days thereafter

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Oropharyngeal Neoplasms
• Salivary Gland Neoplasms
• Salivary Gland Squamous Cell Carcinoma
• Stage II Salivary Gland Cancer
• Stage II Squamous Cell Carcinoma of the Hypopharynx
• Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity
• Stage II Squamous Cell Carcinoma of the Oropharynx
• Stage II Verrucous Carcinoma of the Oral Cavity
• Stage III Salivary Gland Cancer
• Stage III Squamous Cell Carcinoma of the Hypopharynx
• Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
• Stage III Squamous Cell Carcinoma of the Oropharynx
• Stage III Verrucous Carcinoma of the Oral Cavity
• Stage IV Salivary Gland Cancer
• Stage IV Squamous Cell Carcinoma of the Hypopharynx
• Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
• Stage IV Squamous Cell Carcinoma of the Oropharynx
• Stage IV Verrucous Carcinoma of the Oral Cavity

Intervention

Radiation:
• intensity-modulated radiation therapy
Undergo intensity-modulated image-guided adaptive radiotherapy

Drug:
• cisplatin
Given IV

Radiation:
• image-guided adaptive radiation therapy
Undergo intensity-modulated image-guided adaptive radiotherapy

Other:
• 3'-deoxy-3'-[18F]fluorothymidine
Undergo FLT-PET scans for IMRT/IGART

Procedure:
• positron emission tomography/computed tomography
Undergo FDG/FLT-PET scans for IMRT/IGARTT

Radiation:
• fludeoxyglucose F 18
Undergo FDG-PET scans for IMRT/IGART

Locations

Country	Name	City	State
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility of integrating molecular imaging (PET with FLT tracer) into current state-of-the-art image-guided adaptive radiation therapy (IGART) of head and neck cancer		6 weeks	No
Secondary	Comparison of gross tumor volumes defined by FDG-PET, FLT-PET, CBCT, and regular FBCT		Before, during, and following completion of chemoradiation therapy	No
Secondary	Impact of escalated doses to tumor sub-volumes with high FLT and FDG uptake using post-treatment FDG images as an early surrogate for sub-volume-specific local control		Prior to and during radiation therapy	No
Secondary	Development of a database consisting of all molecular and anatomic images, including daily CBCT data sets, obtained during chemo-radiation therapy to support further research		Up to 5 years	No
Secondary	Patient long-term toxicities and survival		At 2 and 4 weeks, 2, 3, 4, 5, 6, 9, and 12 months, every 6 months for 2 years, and then annually for 2 years	Yes
Secondary	Impact of daily image-guided setup; off-line every other week adaptive re-planning; and molecular-image based targeting on sparing of tissues and organs responsible for late and early treatment sequelae		At 2 and 4 weeks, 2, 3, 4, 5, 6, 9, and 12 months, every 6 months for 2 years, and then annually for 2 years	No