Using Fluorine-18-Labeled Fluoro-Misonidazole Positron Emission Tomography To Detect Hypoxia in Head and Neck Cancer Patients

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00606294
• Collaborator: (none)
• Enrollment: 216
• Locations: 5
• Arms: 2
• Anticipated Duration (Months): 228
• Patients Per Site: 43.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The main purpose of this study is to evaluate low oxygen areas called hypoxia within tumors. These low oxygen areas are thought to be the reason why tumors are more resistant to chemotherapy and radiation treatment.

An imaging technique using a hypoxia tracer called fluoromisonidazole (FMISO) can detect low oxygen areas within a tumor. This imaging technique, called a PET scan, uses positively charged particles to detect slight changes in the body's biochemistry and metabolism. FMISO PET scans have been performed in patients with head and neck cancer and have shown the ability to detect low oxygen areas within tumors.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Radiation: fluorine-18-labeled fluoro-misonidazole (18F-FMISO); Device: 18F-FMISO PET scan; Device: MRI; Device: FDG PET/CT scan	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 216 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Study Using Fluorine-18-Labeled Fluoro-Misonidazole Positron Emission Tomography To Detect Hypoxia in Head and Neck Cancer Patients
• Actual Study Start Date: Jun 1, 2004
• Actual Primary Completion Date: Aug 1, 2019
• Anticipated Study Completion Date: Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 (closed to accrual) Cohort 1 (closed to accrual) Cohort 1 (closed to accrual) There will be no change or intervention in a patient's treatment regime using chemoradiation where both the primary and the neck nodes receive 70Gy. This is currently one accepted standard of care. In a subcohort of patients in Cohort 1 with tumors that are positive for HPV who exhibited no evidence of hypoxia on their baseline 18F-FMISO PET/ CT scan or whose tumors have early resolution of hypoxia on their repeat early response 18F-FMISO PET/CT scan will undergo an alternative treatment where the primary tumor site receives 70Gy while the neck nodes receive 60Gy followed by a planned FDG PET/CT scan and observation.	Radiation: fluorine-18-labeled fluoro-misonidazole (18F-FMISO); Device: 18F-FMISO PET scan; Device: MRI; Device: FDG PET/CT scan
Experimental: Cohort 2 (closed to accrual) Experimental: Cohort 2 (closed to accrual) Cohort 2 HPV+ tumors that demonstrate no evidence of hypoxia on an 18F-FMISO PET scan will receive 30Gy to the surgical bed and neck lymph nodes concurrent with standard chemotherapy followed by a 3-4 month post-treatment neck dissection. In patients who exhibit a complete response with this method of treatment, no further treatment is necessary. For patients within this select group who still have pathologic nodal disease, further standard chemoradiation will be given. All other patients in this cohort (i.e. those who are not in the select HPV+ tumor group outlined above) will receive standard of care treatment following their surgery.	Radiation: fluorine-18-labeled fluoro-misonidazole (18F-FMISO); Device: 18F-FMISO PET scan; Device: MRI; Device: FDG PET/CT scan

Outcome Measures

Primary Outcome Measures

1. To Report Positive Versus Negative Hypoxia Among Head and Neck Cancers Using 18F-FMISO Dynamic PET [4 months]

   For Cohort 1

2. To Determine the Pathologic Complete Response of Low Risk HPV+ Oropharyngeal Cancer Patients Without Hypoxia on 18F-FMISO PET Who Received 30Gy [4 months]

   For Cohort 2 - Feasibility will be determined by the pathologic response rate at time of neck dissection

3. Improve the Accuracy of Hypoxia Imaging for Head and Neck Cancers Through Pixel by Pixel Kinetic Analysis of 18F-FMISO Tracer of Dynamic PET Images [At baseline]

   Cohort 2

Secondary Outcome Measures

1. To Detect on Repeat 18F-FMISO PET/CT Scans Whether There is a Reduction of the FMISO-avid or GTVh 5 to 10 Days Into Treatment With Standard Chemoradiotherapy for a Series of Locally Advanced Head and Neck Cancers. [2 weeks from time of scan]

   For Cohort 1

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria for Cohort 1 and Cohort 2 :

• Histologically confirmed diagnosis of head and neck carcinoma (excluding nasopharynx, paranasal sinus, salivary, and thyroid malignancies)Any unknown primary squamous cell carcinoma of head and neck with gross nodes is allowed (2002 AJCC)

• 18 years of age or older

• Must not have received prior radiation therapy or chemotherapy for this diagnosis. Patients who have had their primary site tumor removed by surgery but still present with grossly enlarged lymph nodes are eligible for this study.

• Karnofsky performance status ≥ 70.

Exclusion Criteria for Cohort 1 and Cohort 2:

• all nasopharyngeal, paranasal sinus, salivary cancer, and thyroid malignancies

• prior chemotherapy or radiotherapy within the last three years

• patients that underwent previous surgical resection for the same disease (except for biopsy or surgery removing primary site tumor but still present with grossly enlarged lymph nodes)

• any prior radiotherapy to the head and neck region

• pregnant (confirmed by serum b-HCG in women of reproductive age) or breast feeding

Subject Exclusion Criteria for Optional Contrast MRIs

• Subjects with a known contraindication to the standard MRI contrast agent (Gadavist, a gadolinium-based contrast agent) and/or a recent estimated glomerular filtration rate (eGFR) of 30 or less will be excluded from all DCE-MRIs, and will instead receive non-contrast MRIs at the DCE-MRI time points.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center at Basking Ridge	Basking Ridge	New Jersey	United States
2	Memorial Sloan Kettering Cancer Center at Commack	Commack	New York	United States	11725
3	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
4	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
5	Memorial Sloan Kettering Cancer Center at Mercy Medical Center	Rockville Centre	New York	United States	11570

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Nancy Lee, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 1, 2020

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00606294
• Other Study ID Numbers: 04-070
• First Posted: Feb 1, 2008
• Last Update Posted: Jul 20, 2022
• Last Verified: Jul 1, 2022

• Keywords provided by Memorial Sloan Kettering Cancer Center: Head; Neck; 04-070
• Additional relevant MeSH terms: Head and Neck Neoplasms; Hypoxia; Misonidazole

Study Results

Participant Flow

Arm/Group Title	Cohort 1 (Closed to Accrual)	Cohort 2 (Closed to Accrual)
Arm/Group Description	Cohort 1 (closed to accrual) Cohort 1 (closed to accrual) There will be no change or intervention in a patient's treatment regime using chemoradiation where both the primary and the neck nodes receive 70Gy. This is currently one accepted standard of care. In a subcohort of patients in Cohort 1 with tumors that are positive for HPV who exhibited no evidence of hypoxia on their baseline 18F-FMISO PET/ CT scan or whose tumors have early resolution of hypoxia on their repeat early response 18F-FMISO PET/CT scan will undergo an alternative treatment where the primary tumor site receives 70Gy while the neck nodes receive 60Gy followed by a planned FDG PET/CT scan and observation.	Cohort 2 (closed to accrual) Cohort 2 HPV+ tumors that demonstrate no evidence of hypoxia on an 18F-FMISO PET scan will receive 30Gy to the surgical bed and neck lymph nodes concurrent with standard chemotherapy followed by a 3-4 month post-treatment neck dissection. In patients who exhibit a complete response with this method of treatment, no further treatment is necessary. For patients within this select group who still have pathologic nodal disease, further standard chemoradiation will be given. All other patients in this cohort (i.e. those who are not in the select HPV+ tumor group outlined above) will receive standard of care treatment following their surgery.
Period Title: Overall Study
STARTED	197	19
COMPLETED	161	19
NOT COMPLETED	36	0

Baseline Characteristics

Arm/Group Title	Cohort 1 (Closed to Accrual)	Cohort 2 (Closed to Accrual)	Total
Arm/Group Description	Cohort 1 (closed to accrual) Cohort 1 (closed to accrual) There will be no change or intervention in a patient's treatment regime using chemoradiation where both the primary and the neck nodes receive 70Gy. This is currently one accepted standard of care. In a subcohort of patients in Cohort 1 with tumors that are positive for HPV who exhibited no evidence of hypoxia on their baseline 18F-FMISO PET/ CT scan or whose tumors have early resolution of hypoxia on their repeat early response 18F-FMISO PET/CT scan will undergo an alternative treatment where the primary tumor site receives 70Gy while the neck nodes receive 60Gy followed by a planned FDG PET/CT scan and observation.	Cohort 2 (closed to accrual) Cohort 2 HPV+ tumors that demonstrate no evidence of hypoxia on an 18F-FMISO PET scan will receive 30Gy to the surgical bed and neck lymph nodes concurrent with standard chemotherapy followed by a 3-4 month post-treatment neck dissection. In patients who exhibit a complete response with this method of treatment, no further treatment is necessary. For patients within this select group who still have pathologic nodal disease, further standard chemoradiation will be given. All other patients in this cohort (i.e. those who are not in the select HPV+ tumor group outlined above) will receive standard of care treatment following their surgery.	Total of all reporting groups
Overall Participants	197	19	216
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58	57	58
Sex: Female, Male (Count of Participants)
Female	23 11.7%	3 15.8%	26 12%
Male	174 88.3%	16 84.2%	190 88%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 4.1%	1 5.3%	9 4.2%
Not Hispanic or Latino	189 95.9%	18 94.7%	207 95.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 1.5%	0 0%	3 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	10 5.1%	0 0%	10 4.6%
White	166 84.3%	17 89.5%	183 84.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	18 9.1%	2 10.5%	20 9.3%
Region of Enrollment (Count of Participants)
United States	197 100%	19 100%	216 100%

Outcome Measures

1. Primary Outcome

Title	To Report Positive Versus Negative Hypoxia Among Head and Neck Cancers Using 18F-FMISO Dynamic PET
Description	For Cohort 1
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

This objective is for Cohort 1 participants.

Arm/Group Title	Cohort 1 (Closed to Accrual)	Cohort 2 (Closed to Accrual)
Arm/Group Description	Cohort 1 (closed to accrual) Cohort 1 (closed to accrual) There will be no change or intervention in a patient's treatment regime using chemoradiation where both the primary and the neck nodes receive 70Gy. This is currently one accepted standard of care. In a subcohort of patients in Cohort 1 with tumors that are positive for HPV who exhibited no evidence of hypoxia on their baseline 18F-FMISO PET/ CT scan or whose tumors have early resolution of hypoxia on their repeat early response 18F-FMISO PET/CT scan will undergo an alternative treatment where the primary tumor site receives 70Gy while the neck nodes receive 60Gy followed by a planned FDG PET/CT scan and observation.	Cohort 2 (closed to accrual) Cohort 2 HPV+ tumors that demonstrate no evidence of hypoxia on an 18F-FMISO PET scan will receive 30Gy to the surgical bed and neck lymph nodes concurrent with standard chemotherapy followed by a 3-4 month post-treatment neck dissection. In patients who exhibit a complete response with this method of treatment, no further treatment is necessary. For patients within this select group who still have pathologic nodal disease, further standard chemoradiation will be given. All other patients in this cohort (i.e. those who are not in the select HPV+ tumor group outlined above) will receive standard of care treatment following their surgery.
Measure Participants	197	0
Participants who are hypoxia positive	135 68.5%	0 0%
Participants who are hypoxia negative	26 13.2%	0 0%
Participants declined scans	36 18.3%	0 0%

2. Primary Outcome

Title	To Determine the Pathologic Complete Response of Low Risk HPV+ Oropharyngeal Cancer Patients Without Hypoxia on 18F-FMISO PET Who Received 30Gy
Description	For Cohort 2 - Feasibility will be determined by the pathologic response rate at time of neck dissection
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

This objective is for Cohort 2 participants.

Arm/Group Title	Cohort 1 (Closed to Accrual)	Cohort 2 (Closed to Accrual)
Arm/Group Description	Cohort 1 (closed to accrual) Cohort 1 (closed to accrual) There will be no change or intervention in a patient's treatment regime using chemoradiation where both the primary and the neck nodes receive 70Gy. This is currently one accepted standard of care. In a subcohort of patients in Cohort 1 with tumors that are positive for HPV who exhibited no evidence of hypoxia on their baseline 18F-FMISO PET/ CT scan or whose tumors have early resolution of hypoxia on their repeat early response 18F-FMISO PET/CT scan will undergo an alternative treatment where the primary tumor site receives 70Gy while the neck nodes receive 60Gy followed by a planned FDG PET/CT scan and observation.	Cohort 2 (closed to accrual) Cohort 2 HPV+ tumors that demonstrate no evidence of hypoxia on an 18F-FMISO PET scan will receive 30Gy to the surgical bed and neck lymph nodes concurrent with standard chemotherapy followed by a 3-4 month post-treatment neck dissection. In patients who exhibit a complete response with this method of treatment, no further treatment is necessary. For patients within this select group who still have pathologic nodal disease, further standard chemoradiation will be given. All other patients in this cohort (i.e. those who are not in the select HPV+ tumor group outlined above) will receive standard of care treatment following their surgery.
Measure Participants	0	19
Cohort 2 Pts with a Pathologic Complete Response	0 0%	11 57.9%
Cohort 2 Pts w/out a PathologicComplete Response	0 0%	4 21.1%
Cohort 2 Participants who were not scanned	0 0%	4 21.1%

3. Primary Outcome

Title	Improve the Accuracy of Hypoxia Imaging for Head and Neck Cancers Through Pixel by Pixel Kinetic Analysis of 18F-FMISO Tracer of Dynamic PET Images
Description	Cohort 2
Time Frame	At baseline

Outcome Measure Data

Analysis Population Description

This objective is for Cohort 2 participants.

Arm/Group Title	Cohort 1 (Closed to Accrual)	Cohort 2 (Closed to Accrual)
Arm/Group Description	Cohort 1 (closed to accrual) Cohort 1 (closed to accrual) There will be no change or intervention in a patient's treatment regime using chemoradiation where both the primary and the neck nodes receive 70Gy. This is currently one accepted standard of care. In a subcohort of patients in Cohort 1 with tumors that are positive for HPV who exhibited no evidence of hypoxia on their baseline 18F-FMISO PET/ CT scan or whose tumors have early resolution of hypoxia on their repeat early response 18F-FMISO PET/CT scan will undergo an alternative treatment where the primary tumor site receives 70Gy while the neck nodes receive 60Gy followed by a planned FDG PET/CT scan and observation.	Cohort 2 (closed to accrual) Cohort 2 HPV+ tumors that demonstrate no evidence of hypoxia on an 18F-FMISO PET scan will receive 30Gy to the surgical bed and neck lymph nodes concurrent with standard chemotherapy followed by a 3-4 month post-treatment neck dissection. In patients who exhibit a complete response with this method of treatment, no further treatment is necessary. For patients within this select group who still have pathologic nodal disease, further standard chemoradiation will be given. All other patients in this cohort (i.e. those who are not in the select HPV+ tumor group outlined above) will receive standard of care treatment following their surgery.
Measure Participants	0	19
Cohort 2 Pts Negative at Baseline	0 0%	6 31.6%
Cohort 2 Pts Positive at Baseline at Repeat Scan	0 0%	3 15.8%
Cohort 2 Pts Negative at Baseline at Repeat Scan	0 0%	9 47.4%
Cohort 2 Pts positive at Baseline/withdrew consent	0 0%	1 5.3%

4. Secondary Outcome

Title	To Detect on Repeat 18F-FMISO PET/CT Scans Whether There is a Reduction of the FMISO-avid or GTVh 5 to 10 Days Into Treatment With Standard Chemoradiotherapy for a Series of Locally Advanced Head and Neck Cancers.
Description	For Cohort 1
Time Frame	2 weeks from time of scan

Outcome Measure Data

Analysis Population Description

N/A - data were not collected

Arm/Group Title	Cohort 1 (Closed to Accrual)	Cohort 2 (Closed to Accrual)
Arm/Group Description	Cohort 1 (closed to accrual) Cohort 1 (closed to accrual) There will be no change or intervention in a patient's treatment regime using chemoradiation where both the primary and the neck nodes receive 70Gy. This is currently one accepted standard of care. In a subcohort of patients in Cohort 1 with tumors that are positive for HPV who exhibited no evidence of hypoxia on their baseline 18F-FMISO PET/ CT scan or whose tumors have early resolution of hypoxia on their repeat early response 18F-FMISO PET/CT scan will undergo an alternative treatment where the primary tumor site receives 70Gy while the neck nodes receive 60Gy followed by a planned FDG PET/CT scan and observation.	Cohort 2 (closed to accrual) Cohort 2 HPV+ tumors that demonstrate no evidence of hypoxia on an 18F-FMISO PET scan will receive 30Gy to the surgical bed and neck lymph nodes concurrent with standard chemotherapy followed by a 3-4 month post-treatment neck dissection. In patients who exhibit a complete response with this method of treatment, no further treatment is necessary. For patients within this select group who still have pathologic nodal disease, further standard chemoradiation will be given. All other patients in this cohort (i.e. those who are not in the select HPV+ tumor group outlined above) will receive standard of care treatment following their surgery.
Measure Participants	0	0

Adverse Events

Time Frame	1 year
Arm/Group Title	Cohort 1 (Closed to Accrual)		Cohort 2 (Closed to Accrual)
Arm/Group Description	Cohort 1 (closed to accrual) Cohort 1 (closed to accrual) There will be no change or intervention in a patient's treatment regime using chemoradiation where both the primary and the neck nodes receive 70Gy. This is currently one accepted standard of care. In a subcohort of patients in Cohort 1 with tumors that are positive for HPV who exhibited no evidence of hypoxia on their baseline 18F-FMISO PET/ CT scan or whose tumors have early resolution of hypoxia on their repeat early response 18F-FMISO PET/CT scan will undergo an alternative treatment where the primary tumor site receives 70Gy while the neck nodes receive 60Gy followed by a planned FDG PET/CT scan and observation.		Cohort 2 (closed to accrual) Cohort 2 HPV+ tumors that demonstrate no evidence of hypoxia on an 18F-FMISO PET scan will receive 30Gy to the surgical bed and neck lymph nodes concurrent with standard chemotherapy followed by a 3-4 month post-treatment neck dissection. In patients who exhibit a complete response with this method of treatment, no further treatment is necessary. For patients within this select group who still have pathologic nodal disease, further standard chemoradiation will be given. All other patients in this cohort (i.e. those who are not in the select HPV+ tumor group outlined above) will receive standard of care treatment following their surgery.
All Cause Mortality
	Cohort 1 (Closed to Accrual)		Cohort 2 (Closed to Accrual)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/197 (23.9%)		2/19 (10.5%)
Serious Adverse Events
	Cohort 1 (Closed to Accrual)		Cohort 2 (Closed to Accrual)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/197 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1 (Closed to Accrual)		Cohort 2 (Closed to Accrual)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/197 (0%)		0/19 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.