| ID | Type | Description | Link |
|---|---|---|---|
| HUM 27253 | Other Identifier | University of Michigan Medical IRB |
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Stopped early for funding and efficacy reasons.
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This is a single-arm, phase II trial to characterize the clinical outcome of standard of care, cetuximab concurrent with radiation, in a special population (head and neck cancer patients who cannot tolerate concurrent chemoradiotherapy due to advanced age, poor performance status or concurrent illness), and to determine if biomarker response to a loading dose of cetuximab is predictive of that outcome.
Primary Objective 1: Determine changes in tumor EGFR, pEGFR, downstream signaling and novel phosphoproteins following a loading dose of cetuximab in patients who are poor candidates for chemoradiation (age =70 years or with significant co-morbidities) and are therefore treated with cetuximab with radiation.
Primary Objective 2: Characterize clinical outcomes, including local recurrence, progression-free survival and overall survival in these patients, and correlate these clinical outcomes with the changes in tumor EGFR, pEGFR, downstream signaling, and novel phosphoproteins.
Primary Objective 3: Describe the toxicity, in particular mucositis/dysphagia, of this regimen.
Secondary Objective 1: Conduct normal mucosa EGFR assessment for comparison with tumor sample.
Secondary Objective 2: Correlate HPV presence and titer with p53 status and clinical outcome.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cetuximab | Drug | Patients will receive a single dose of cetuximab 400 mg/m (Day 0). On day 7 (+/- 1 day), a repeat biopsy will be performed. Radiation concurrent with weekly cetuximab 250 mg/m. |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change in Tumor Epidermal Growth Factor Receptor (EGFR) | The ratio (fold change) of tumor EGFR post-loading dose/pre-loading dose of cetuximab. Reported as the mean of fold changes across all participants who had an evaluable tumor sample. | At baseline (pre-loading dose) and day 7 post-loading dose |
| Mean Change in Tumor Phosphorylated EGFR (pEGFR) | The ratio (fold change) of tumor pEGFR post-loading dose/pre-loading dose of cetuximab. Reported as the mean of fold changes across all participants who had an evaluable tumor sample. | At baseline (pre-loading dose) and day 7 post-loading dose |
| Progression Free Survival Rate | Percentage of participants who survived without recurrent disease, from the time of enrollment to 1 and 2 years. | At 1 and 2 years |
| Overall Survival Rate | Percentage of participants alive at 1 and 2 years after enrollment. | At 1 and 2 Years |
| Number of Participants With Treatment Related Toxicities | Toxicities are measured by number of participants who experience one or more types or indicator of toxicity, shown as all grades and grades 3-4. As each participant could have multiple toxicities, the total number of incidents outnumbers the number of participants. Toxicities are graded according to the CTCAE v4. | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Tumor EGFR Level Relative to EGFR in Normal Mucosa | Normal mucosa EGFR was assessed for comparison with EGFR in tumor sample. The fold change in tumor EGFR level at post-loading dose/pre-loading dose of cetuximab, relative to fold change in normal mucosa EGFR level post-loading dose/pre-loading dose of cetuximab was summarized across all participants who had an evaluable tumor sample and normal mucosa sample. The value reported is the ratio of fold change in tumor/fold change in buccal EGFR. |
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Inclusion Criteria:
Patients must have pathologically-confirmed, previously untreated, clinically accessible (without general anesthesia) locally advanced squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or nonresectable head and neck squamous cell carcinomas of the skin.
Patients will be limited to:
Laboratory criteria:
Patients must give documented informed consent to participate in this study.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Shruti Jolly, MD | University of Michigan Rogel Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan Medical Center | Ann Arbor | Michigan | 48109 | United States | ||
| University of Michigan Veterans Administration Hospital |
2 participants withdrew before receiving treatment
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment With Cetuximab + RT | Patients received a single loading dose of cetuximab 400 mg/m (Day 0), then weekly cetuximab 250 mg/m concurrent with radiation. Within approximately 4 days after first (loading) dose of cetuximab, patients received radiation administered as 70 Gy in 35 fractions to the gross tumor, 50-60 Gy to subclinical target volumes. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment: Cetuximab + RT | Patients received a single loading dose of cetuximab and a cetuximab infusion delivered once a week during radiotherapy. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mean Change in Tumor Epidermal Growth Factor Receptor (EGFR) | The ratio (fold change) of tumor EGFR post-loading dose/pre-loading dose of cetuximab. Reported as the mean of fold changes across all participants who had an evaluable tumor sample. | 15 participants had a sample size sufficient for EGFR analysis. | Posted | Mean | Full Range | fold change | At baseline (pre-loading dose) and day 7 post-loading dose |
|
|
3 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment: Cetuximab + RT | Patients received a single loading dose of cetuximab and a cetuximab infusion delivered once a week during radiotherapy. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinus tachycardia | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Shruti Jolly, M.D. | University of Michigan Rogel Cancer Center | 734-936-4302 | shrutij@med.umich.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 3, 2018 | Dec 15, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006258 | Head and Neck Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000068818 | Cetuximab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| 50-60 Gy and 70 Gy | Radiation | Within approximately 4 days (after single dose of Cetuximab), definitive radiation will begin (70 Gy in 35 fractions to the gross tumor, 50-60 Gy to subclinical target volumes) concurrent with weekly cetuximab 250 mg/m. |
|
| At baseline (pre-loading dose) and day 7 post-loading dose |
| Change in Tumor pEGFR Level Relative to pEGFR in Normal Mucosa | Normal mucosa pEGFR was assessed for comparison with pEGFR in tumor sample. The fold change in tumor pEGFR level post-loading dose/pre loading dose of cetuximab, relative to fold change in normal mucosa pEGFR level post-loading dose/pre-loading dose of cetuximab was summarized across all participants who had an evaluable tumor sample and normal mucosa sample. The value reported is the ratio of fold change in tumor/fold change in buccal pEGFR. | At baseline (pre-loading dose) and day 7 post-loading dose |
| Ann Arbor |
| Michigan |
| 48109 |
| United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Smoking Status | Count of Participants | Participants |
|
| Cancer Location | Count of Participants | Participants |
|
| HPV Status | Count of Participants | Participants |
|
| Participants |
|
|
| Primary | Mean Change in Tumor Phosphorylated EGFR (pEGFR) | The ratio (fold change) of tumor pEGFR post-loading dose/pre-loading dose of cetuximab. Reported as the mean of fold changes across all participants who had an evaluable tumor sample. | 10 participants had a sample size sufficient for pEGFR analysis. | Posted | Mean | Full Range | fold change | At baseline (pre-loading dose) and day 7 post-loading dose |
|
|
|
| Primary | Progression Free Survival Rate | Percentage of participants who survived without recurrent disease, from the time of enrollment to 1 and 2 years. | Patients who completed the full course of cetuximab+RT or had cetuximab+RT stopped for toxicity. | Posted | Number | 95% Confidence Interval | percentage of participants | At 1 and 2 years |
|
|
|
|
| Primary | Overall Survival Rate | Percentage of participants alive at 1 and 2 years after enrollment. | Patients who completed the full course of cetuximab+RT or had cetuximab+RT stopped for toxicity. | Posted | Number | 95% Confidence Interval | percentage of participants | At 1 and 2 Years |
|
|
|
|
| Primary | Number of Participants With Treatment Related Toxicities | Toxicities are measured by number of participants who experience one or more types or indicator of toxicity, shown as all grades and grades 3-4. As each participant could have multiple toxicities, the total number of incidents outnumbers the number of participants. Toxicities are graded according to the CTCAE v4. | Posted | Number | participants | 3 years |
|
|
|
| Secondary | Change in Tumor EGFR Level Relative to EGFR in Normal Mucosa | Normal mucosa EGFR was assessed for comparison with EGFR in tumor sample. The fold change in tumor EGFR level at post-loading dose/pre-loading dose of cetuximab, relative to fold change in normal mucosa EGFR level post-loading dose/pre-loading dose of cetuximab was summarized across all participants who had an evaluable tumor sample and normal mucosa sample. The value reported is the ratio of fold change in tumor/fold change in buccal EGFR. | 6 participants had a sample size sufficient for EGFR analysis. | Posted | Mean | Full Range | ratio | At baseline (pre-loading dose) and day 7 post-loading dose |
|
|
|
| Secondary | Change in Tumor pEGFR Level Relative to pEGFR in Normal Mucosa | Normal mucosa pEGFR was assessed for comparison with pEGFR in tumor sample. The fold change in tumor pEGFR level post-loading dose/pre loading dose of cetuximab, relative to fold change in normal mucosa pEGFR level post-loading dose/pre-loading dose of cetuximab was summarized across all participants who had an evaluable tumor sample and normal mucosa sample. The value reported is the ratio of fold change in tumor/fold change in buccal pEGFR. | 7 participants had a sample size sufficient for pEGFR analysis. | Posted | Mean | Full Range | ratio | At baseline (pre-loading dose) and day 7 post-loading dose |
|
|
|
| Post-Hoc | Freedom From Local Regional Progression (FFLRP) | Percentage of participants without local or regional failure from the time of enrollment to 1 and 2 years. | Patients who completed the full course of cetuximab+RT or had cetuximab+RT stopped for toxicity. | Posted | Number | 95% Confidence Interval | percentage of participants | At 1 and 2 years |
|
|
|
|
| 12 |
| 21 |
| 12 |
| 21 |
| 20 |
| 21 |
| Ventricular fibrillation | Cardiac disorders | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | Systematic Assessment |
|
| Esophagitis | Gastrointestinal disorders | Systematic Assessment |
|
| Gastrointestinal disorders - Unspecified | Gastrointestinal disorders | Systematic Assessment |
|
| Mucositis oral | Gastrointestinal disorders | Systematic Assessment |
|
| Pancreatitis | Gastrointestinal disorders | Systematic Assessment |
|
| Chills | General disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
| Multi-organ failure | General disorders | Systematic Assessment |
|
| Skin infection | Infections and infestations | Systematic Assessment |
|
| Tracheitis | Infections and infestations | Systematic Assessment |
|
| Dermatitis radiation | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
|
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Delirium | Psychiatric disorders | Systematic Assessment |
|
| Psychiatric disorders - Unspecified | Psychiatric disorders | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Stridor | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hypertension | Vascular disorders | Systematic Assessment |
|
| Blood and lymphatic system disorders - Unspecified | Blood and lymphatic system disorders | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | Systematic Assessment |
|
| Esophagitis | Gastrointestinal disorders | Systematic Assessment |
|
| Gastrointestinal disorders - Unspecified | Gastrointestinal disorders | Systematic Assessment |
|
| Mucositis oral | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | Systematic Assessment |
|
| Salivary duct inflammation | Gastrointestinal disorders | Systematic Assessment |
|
| Stomach pain | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Chills | General disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| Papulopustular rash | Infections and infestations | Systematic Assessment |
|
| Dermatitis radiation | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | Systematic Assessment |
|
| Creatinine increased | Investigations | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | Systematic Assessment |
|
| Platelet count decreased | Investigations | Systematic Assessment |
|
| Weight loss | Investigations | Systematic Assessment |
|
| White blood cell decreased | Investigations | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypernatremia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Trismus | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | Systematic Assessment |
|
| Facial muscle weakness | Nervous system disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Myelitis | Nervous system disorders | Systematic Assessment |
|
| Paresthesia | Nervous system disorders | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | Systematic Assessment |
|
| Psychiatric disorders - Unspecified | Psychiatric disorders | Systematic Assessment |
|
| Urinary frequency | Renal and urinary disorders | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Sore throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Nail loss | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Rash acneiform | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Skin and subcutaneous tissue disorders - Unspecified | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Skin ulceration | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Hot flashes | Vascular disorders | Systematic Assessment |
|
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| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| Title | Measurements |
|---|---|
|
| All grades: Hematologic Toxicity |
|
| Grades 3-4: Cutaneous Toxicity |
|
| Grades 3-4: Mucositis |
|
| Grades 3-4: Dysphagia |
|
| Grades 3-4: Hematologic Toxicity |
|