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| ID | Type | Description | Link |
|---|---|---|---|
| HUM 11350 | Other Identifier | University of Michigan Medical IRB |
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The study was discontinued prematurely due to early stopping rules.
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The purpose of this study is to learn how to identify early which patients will respond to chemotherapy plus radiation therapy in order to reduce the number of subjects who require surgery (followed by radiation therapy).
In this study one cycle of chemotherapy will be administered and then those subjects who respond well to that cycle will be started on radiation therapy along with chemotherapy and those that don't respond well to the initial cycle of chemotherapy, will undergo a total laryngectomy (surgery to remove the voice box) followed by radiation therapy. The initial cycle of chemotherapy consists of the drugs Taxotere, Cisplatin, and 5-Fluorouracil (this combination is known as TPF). Then on Day 20 of the study, the subjects will be administered another chemotherapy agent called cetuximab (a.k.a. C-225). It will then be determined if the patient's response to the chemotherapy was favorable by examining the patient's tumor with an endoscopy. If the response is determined to be good, then the patient will continue with a chemotherapy regimen with the addition of radiation therapy combination. If the patient's response to the chemotherapy is determined to be less than favorable, then the patient will be advised to undergo salvage surgery (a.k.a. laryngectomy) to remove their voice box and then undergo radiation therapy treatment. Additionally, tumor tissue samples and blood will be studied to see if there are special molecular markers that help predict when a tumor will respond to chemotherapy and radiation treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chemotherapy/Radiation/Surgery | Experimental | Patients will undergo induction chemotherapy with (TPF): Docetaxel (Taxotere) 75 mg/m2 and cisplatin 100 mg/m2 on day 1, and 5-FU 750 mg/m2 days 1-4. On day 20 patients will receive a single dose of cetuximab (C-225) 400 mg/m2. Depending upon disease response, patients will undergo salvage laryngectomy followed by radiation therapy and chemotherapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cisplatin | Drug | 1. Day 1: 100 mg/m2, administered as an i.v. infusion will run over one hour. 2. Day #23: Subjects with a < 50% response (NR) to induction chemotherapy will undergo salvage laryngectomy followed by RT. Cisplatin will be added to radiation for patients whose surgical pathology reveals high-risk features (i.e. extracapsular spread, > 2 positive lymph nodes, perineural invasion, or positive margins). Cisplatin will either be dosed a 100 mg/m2 every 21 days or 40 mg/m2 weekly at the discretion of the prescribing physician. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Patients Achieving Histologic Complete Response | The proportion of patients treated with radiation+cetuximab achieving histologic CR will be estimated, along with 95% exact confidence intervals. Histologic Complete Response (CR) will be defined as primary tumors exhibiting a clinical CR or at least a 90% PR (Partial Response) along with a negative post-treatment biopsy. | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| The Difference, From Baseline, in EGFR, for Tumor Biopsies Taken After the Administration of Cetuximab Following TPF. | To determine tumor EGFR degradation, as well as other markers of down-stream EGFR inhibition, observed in tumor biopsies taken shortly after the administration of cetuximab following TPF, compared with pre-treatment biopsies. | Day 23 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Francis P. Worden, M.D. | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | 48109-0848 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Chemotherapy/Radiation/Surgery | Patients will undergo induction chemotherapy with (TPF): Docetaxel (Taxotere) 75 mg/m2 and cisplatin 100 mg/m2 on day 1, and 5-FU 750 mg/m2 days 1-4. On day 20 patients will receive a single dose of cetuximab (C-225) 400 mg/m2. Depending upon disease response, patients will undergo salvage laryngectomy followed by radiation therapy and chemotherapy. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Chemotherapy/Radiation/Surgery | Patients will undergo induction chemotherapy with (TPF): Docetaxel (Taxotere) 75 mg/m2 and cisplatin 100 mg/m2 on day 1, and 5-FU 750 mg/m2 days 1-4. On day 20 patients will receive a single dose of cetuximab (C-225) 400 mg/m2. Depending upon disease response, patients will undergo salvage laryngectomy followed by radiation therapy and chemotherapy. |
| 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 | Percentage of Patients Achieving Histologic Complete Response | The proportion of patients treated with radiation+cetuximab achieving histologic CR will be estimated, along with 95% exact confidence intervals. Histologic Complete Response (CR) will be defined as primary tumors exhibiting a clinical CR or at least a 90% PR (Partial Response) along with a negative post-treatment biopsy. | The study was discontinued prematurely due to an early stopping rule. No participants were assessed for the primary outcome because an insufficient number of patients were recruited. | Posted | 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 | Chemotherapy/Radiation/Surgery | Patients will undergo induction chemotherapy with (TPF): Docetaxel (Taxotere) 75 mg/m2 and cisplatin 100 mg/m2 on day 1, and 5-FU 750 mg/m2 days 1-4. On day 20 patients will receive a single dose of cetuximab (C-225) 400 mg/m2. Depending upon disease response, patients will undergo salvage laryngectomy followed by radiation therapy and chemotherapy. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dehydration | Metabolism and nutrition disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tinnitus | Ear and labyrinth disorders |
The study was discontinued prematurely due to an early stopping rule.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Francis Worden | University of Michigan Comprehensive Cancer Center | 734-936-0453 | fworden@umich.edu |
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| ID | Term |
|---|---|
| D007822 | Laryngeal Neoplasms |
| ID | Term |
|---|---|
| D010039 | Otorhinolaryngologic Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D002945 | Cisplatin |
| D000068818 | Cetuximab |
| D005472 | Fluorouracil |
| D000077143 | Docetaxel |
| ID | Term |
|---|---|
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
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|
|
| Cetuximab | Drug | 1. Cetuximab will be administered at 400 mg/m2 on Day 20 (2 hour administration). 2. Cetuximab will be administered in combination with radiation therapy to those subjects who had a Partial or Complete response after the first cycle of the chemotherapy regimen is administered. The dosage for these administrations is 250 mg/m2 over sixty minutes and it will be administered for six weeks. |
|
|
| 5-Fluorouracil | Drug | 5-FU will be administered 750 mg/m2 in 0.9% normal saline as a 24-hour continuous infusion, days #1-4. |
|
|
| Docetaxel | Drug | 75 mg/m2 by I.V. over one hour on Day # 1 only |
|
|
| The Change in Overall Quality of Life Score During Radiation Therapy and at 6, 12, and 24 Months Post Treatment. | To evaluate the quality of life (QOL). | 24 months |
| Overall Survival Time | To determine the overall survival rates compared to the overall survival rates of historical controls. | 3 years |
| The Number of Patients That Experience Grade 3 and 4 Mucositis or Dysphagia | To determine and compare toxicities, most notably mucositis and dysphagia, in patients on this treatment regimen as compared to historical controls. | 3 years. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
| Secondary | The Difference, From Baseline, in EGFR, for Tumor Biopsies Taken After the Administration of Cetuximab Following TPF. | To determine tumor EGFR degradation, as well as other markers of down-stream EGFR inhibition, observed in tumor biopsies taken shortly after the administration of cetuximab following TPF, compared with pre-treatment biopsies. | The study was discontinued prematurely due to an early stopping rule. No participants were assessed because an insufficient number of patients were recruited. | Posted | Day 23 |
|
|
| Secondary | The Change in Overall Quality of Life Score During Radiation Therapy and at 6, 12, and 24 Months Post Treatment. | To evaluate the quality of life (QOL). | The study was discontinued prematurely due to an early stopping rule. No participants were assessed because an insufficient number of patients were recruited. | Posted | 24 months |
|
|
| Secondary | Overall Survival Time | To determine the overall survival rates compared to the overall survival rates of historical controls. | The study was discontinued prematurely due to an early stopping rule. No participants were assessed because an insufficient number of patients were recruited. | Posted | 3 years |
|
|
| Secondary | The Number of Patients That Experience Grade 3 and 4 Mucositis or Dysphagia | To determine and compare toxicities, most notably mucositis and dysphagia, in patients on this treatment regimen as compared to historical controls. | The study was discontinued prematurely due to an early stopping rule. No participants were assessed because an insufficient number of patients were recruited. | Posted | 3 years. |
|
|
| 2 |
| 4 |
| 4 |
| 4 |
| Diarrhea | Gastrointestinal disorders |
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| Nausea | Gastrointestinal disorders |
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| Colitis, Infection | Gastrointestinal disorders |
|
| Febrile Neutropenia | Blood and lymphatic system disorders |
|
| Infection with Grade 3-4 Neutrophils | Infections and infestations |
|
| Hemoglobin | Blood and lymphatic system disorders |
|
| Neutrophils/granulocytes | Blood and lymphatic system disorders |
|
| Fatigue | General disorders |
|
| Insomnia | Psychiatric disorders |
|
| Weight loss | General disorders |
|
| Dermatology/Skin - Other | Skin and subcutaneous tissue disorders |
|
| Hair loss/alopecia (scalp or body) | Skin and subcutaneous tissue disorders |
|
| Rash/desquamation | Skin and subcutaneous tissue disorders |
|
| Rash: dermatitis associated with radiation | Skin and subcutaneous tissue disorders |
|
| Skin breakdown/decubitus ulcer | Skin and subcutaneous tissue disorders |
|
| Anorexia | Gastrointestinal disorders |
|
| Constipation | Gastrointestinal disorders |
|
| Dehydration | Gastrointestinal disorders |
|
| Diarrhea | Gastrointestinal disorders |
|
| Dry mouth/salivary gland (xerostomia) | Gastrointestinal disorders |
|
| Dysphagia (difficulty swallowing) | Gastrointestinal disorders |
|
| Esophagitis | Gastrointestinal disorders |
|
| Heartburn/dyspepsia | Gastrointestinal disorders |
|
| Mucositis/stomatitis (clinical exam), Oral Cavity | Investigations |
|
| Mucositis/stomatitis (clinical exam), Pharynx | Investigations |
|
| Mucositis/stomatitis (functional/symptomatic), Oral Cavity | Gastrointestinal disorders |
|
| Mucositis/stomatitis (functional/symptomatic), Pharynx | Gastrointestinal disorders |
|
| Nausea | Gastrointestinal disorders |
|
| Vomiting | Gastrointestinal disorders |
|
| Colitis, infectious (e.g., Clostridium difficile) | Infections and infestations |
|
| Febrile neutropenia | Infections and infestations |
|
| Skin Infection with Grade 3 or 4 neutrophils | Skin and subcutaneous tissue disorders |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils (Foreign Body) | Infections and infestations |
|
| Infection (Upper Aerodigestive, NOS) | Respiratory, thoracic and mediastinal disorders |
|
| Infection (Upper Airway, NOS) | Respiratory, thoracic and mediastinal disorders |
|
| Infection with unknown ANC (Upper Aerodigestive) | Respiratory, thoracic and mediastinal disorders |
|
| Muscle weakness, Extremity-lower | Musculoskeletal and connective tissue disorders |
|
| Muscle weakness, Whole body/generalized | Musculoskeletal and connective tissue disorders |
|
| Confusion | Nervous system disorders |
|
| Mood alteration | Nervous system disorders |
|
| Ocular/Visual - Other (Specify) | Eye disorders |
|
| Back Pain | Musculoskeletal and connective tissue disorders |
|
| Chest Pain | Cardiac disorders |
|
| Head Pain | Nervous system disorders |
|
| Oral Pain | Gastrointestinal disorders |
|
| Throat Pain | Gastrointestinal disorders |
|
| Aspiration | Respiratory, thoracic and mediastinal disorders |
|
| Fistula, pulmonary/upper respiratory | Respiratory, thoracic and mediastinal disorders |
|
| Pulmonary/Upper Respiratory - Other (Specify) | Respiratory, thoracic and mediastinal disorders |
|
| Sexual/Reproductive Function - Other (Specify) | Reproductive system and breast disorders |
|
| Rash: acne/acneiform | Skin and subcutaneous tissue disorders |
|
| Hyperglycemia | Metabolism and nutrition disorders |
|
| Hypocalcemia | Metabolism and nutrition disorders |
|
| Hypokalemia | Metabolism and nutrition disorders |
|
| Hypophosphatemia | Metabolism and nutrition disorders |
|
| Leukopenia | Blood and lymphatic system disorders |
|
| Lymphopenia | Blood and lymphatic system disorders |
|
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| D007818 |
| Laryngeal Diseases |
| D012140 | Respiratory Tract Diseases |
| D012142 | Respiratory Tract Neoplasms |
| D010038 | Otorhinolaryngologic Diseases |
| D061067 |
| Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |