Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to demonstrate the activity (response rate and rate of stable disease) of Iressa administered as a single agent escalated to a dose that produces grade 2 skin toxicity in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN).
This open-label, multi-institution, phase II study evaluated the activity of gefitinib at individually escalated doses up to 750mg to achieve the skin toxicity grade greater than or equal to 2. Patients were started on gefitinib 250mg orally daily for 2 weeks. At 2 weeks, patients were reevaluated and given skin toxicity grade according to the National Cancer Institute Common Toxicity Criteria version 3.0 (CTC 3.0). Patients with grade 2 or greater skin toxicity remained on 250 mg daily; in patients with grade 0-1 skin toxicity the dose was escalated to 500 mg daily and again to 750 mg daily on next evaluation until grade 2 or greater skin toxicity was developed.
The protocol was later amended because of the reported lower efficacy of the 250 mg dose and patients were then started at 500 mg per day. There was no further dose escalation beyond 750 mg per day irrespective of the response or grade of skin toxicity. Therapy was discontinued upon disease progression, unacceptable toxicity, death or patient's withdrawal of consent. Dose interruptions were used as the first approach to managing the toxicity of the patients who experienced grade 3-4 non-hematological toxicities. Gefitinib was interrupted for up to a maximum of 14 days until the toxicities dropped to grade 1 or less. Adherence to therapy was monitored using drug diaries that were collected at each physician visit and assessed against pill counts.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Gefitinib | Experimental | Patients were started on gefitinib 250 mg orally daily for 2 weeks. At 2 weeks, patients were reevaluated and given skin toxicity grade according to the National Cancer Institute Common Toxicity Criteria version 3.0 (CTC 3.0). Patients with grade 2 or greater skin toxicity remained on 250 mg daily; in patients with grade 0-1 skin toxicity the dose 250-mg oral dose-escalating dose; each patient received treatment at the dose that produced grade 2 skin toxicity until disease progression or withdrawal. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gefitinib | Drug | Patients were started on gefitinib 250 mg orally daily for 2 weeks. At 2 weeks, patients were reevaluated and given skin toxicity grade according to the National Cancer Institute Common Toxicity Criteria version 3.0 (CTC 3.0). Patients with grade 2 or greater skin toxicity remained on 250 mg daily; in patients with grade 0-1 skin toxicity the dose 250-mg oral dose-escalating dose; each patient received treatment at the dose that produced grade 2 skin toxicity until disease progression or withdrawal. |
| Measure | Description | Time Frame |
|---|---|---|
| Response (CR or PR), Stable Disease (SD), and Progressive Disease (PD) Rates | The proportion of subjects that responded [complete (CR) or partial response (PR)], had stable disease (SD), or progressive disease (PD) as defined by the Response Evaluation Criteria In Solid Tumors (RECIST) Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter (LD) since the treatment started Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Median Progression-free Survival Time | Progression-free survival (PFS) is the number of months during and after Gefitinib treatment during which the cancer did not get worse (progress) as defined by Response Evaluation Criteria In Solid Tumors (RECIST). Progressive disease is associated with at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. All patients developed progressive disease or died during the 9-month observation period. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Ezra EW Cohen, MD | University of Chicago | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Miami Sylvester Comprehensive Cancer Center | Miami | Florida | 33136 | United States | ||
| Northwestern University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22513208 | Result | Perez CA, Song H, Raez LE, Agulnik M, Grushko TA, Dekker A, Stenson K, Blair EA, Olopade OI, Seiwert TY, Vokes EE, Cohen EE. Phase II study of gefitinib adaptive dose escalation to skin toxicity in recurrent or metastatic squamous cell carcinoma of the head and neck. Oral Oncol. 2012 Sep;48(9):887-92. doi: 10.1016/j.oraloncology.2012.03.020. Epub 2012 Apr 17. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Gefitinib | Patients were started on gefitinib 250 mg orally daily for 2 weeks. At 2 weeks, patients were reevaluated and given skin toxicity grade according to the National Cancer Institute Common Toxicity Criteria version 3.0 (CTC 3.0). Patients with grade 2 or greater skin toxicity remained on 250 mg daily; in patients with grade 0-1 skin toxicity the dose 250-mg oral dose-escalating dose; each patient received treatment at the dose that produced grade 2 skin toxicity until disease progression or withdrawal. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Gefitinib | Patients were started on gefitinib 250 mg orally daily for 2 weeks. At 2 weeks, patients were reevaluated and given skin toxicity grade according to the National Cancer Institute Common Toxicity Criteria version 3.0 (CTC 3.0). Patients with grade 2 or greater skin toxicity remained on 250 mg daily; in patients with grade 0-1 skin toxicity the dose 250-mg oral dose-escalating dose; each patient received treatment at the dose that produced grade 2 skin toxicity until disease progression or withdrawal. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| 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 | Response (CR or PR), Stable Disease (SD), and Progressive Disease (PD) Rates | The proportion of subjects that responded [complete (CR) or partial response (PR)], had stable disease (SD), or progressive disease (PD) as defined by the Response Evaluation Criteria In Solid Tumors (RECIST) Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter (LD) since the treatment started Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions | Eight patients were not assessable for response, six of them died prior to the evaluation of response. For the purpose of the analysis these patients were classified as having disease progression in response to therapy. | Posted | Number | percentage of participants | 8 weeks |
Adverse events were recorded during the 9-month observation period (including treatment phase and follow-up).
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Gefitinib | Patients were started on gefitinib 250 mg orally daily for 2 weeks. At 2 weeks, patients were reevaluated and given skin toxicity grade according to the National Cancer Institute Common Toxicity Criteria version 3.0 (CTC 3.0). Patients with grade 2 or greater skin toxicity remained on 250 mg daily; in patients with grade 0-1 skin toxicity the dose 250-mg oral dose-escalating dose; each patient received treatment at the dose that produced grade 2 skin toxicity until disease progression or withdrawal. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute renal failure | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment | Acute kidney failure is the rapid loss the kidneys' ability to remove waste and help balance fluids and electrolytes in the body. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dehydration | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment | "Dehydration (hypohydration) is the excessive loss of body water, with an accompanying disruption of metabolic processes." |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tanguy Lim-Seiwert | The University of Chicago | 773-702-2452 | seiwert@uchicago.edu |
Not provided
| ID | Term |
|---|---|
| D006258 | Head and Neck Neoplasms |
| D009369 | Neoplasms |
| D002277 | Carcinoma |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077156 | Gefitinib |
| ID | Term |
|---|---|
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| 9 months |
| Chicago |
| Illinois |
| 60611 |
| United States |
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Gefitinib | Patients were started on gefitinib 250 mg orally daily for 2 weeks. At 2 weeks, patients were reevaluated and given skin toxicity grade according to the National Cancer Institute Common Toxicity Criteria version 3.0 (CTC 3.0). Patients with grade 2 or greater skin toxicity remained on 250 mg daily; in patients with grade 0-1 skin toxicity the dose 250-mg oral dose-escalating dose; each patient received treatment at the dose that produced grade 2 skin toxicity until disease progression or withdrawal. |
|
|
| Secondary | Median Progression-free Survival Time | Progression-free survival (PFS) is the number of months during and after Gefitinib treatment during which the cancer did not get worse (progress) as defined by Response Evaluation Criteria In Solid Tumors (RECIST). Progressive disease is associated with at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. All patients developed progressive disease or died during the 9-month observation period. | Posted | Median | 95% Confidence Interval | months | 9 months |
|
|
|
| 20 |
| 44 |
| 17 |
| 44 |
|
| Aspiration pneumonia | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment | "Aspiration pneumonia isbronchopneumonia that develops due to the entrance of foreign materials into the bronchial tree,[1] usually oral or gastric contents (including food, saliva, or nasal secretions). " |
|
| Atrial fibrillation | Cardiac disorders | CTCAE (3.0) | Systematic Assessment | "Atrial fibrillation is an irregular and often rapid heart rate that commonly causes poor blood flow to the body. During atrial fibrillation, the heart's atria beat chaotically and irregularly, out of coordination with the ventricles of the heart" |
|
| Bleeding from tumor site | General disorders | CTCAE (3.0) | Systematic Assessment | Bleeding from tumor site |
|
| Bleeding from unspecified region | General disorders | CTCAE (3.0) | Systematic Assessment | Bleeding from unspecified region |
|
| Dehydration | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment | "Dehydration (hypohydration) is the excessive loss of body water, with an accompanying disruption of metabolic processes." |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment | Diarrhea is the condition of having three or more loose or liquid bowel movements per day. |
|
| Dysphagia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment | Dysphagia is the medical term for the symptom of difficulty in swallowing. |
|
| Fever | General disorders | CTCAE (3.0) | Systematic Assessment | Fever is characterized by an elevation of body temperature above the normal range of 36.5-37.5 degrees C (97.7-99.5 degrees F) due to an increase in the temperature regulatory set-point. |
|
| G-tube malfunction | General disorders | CTCAE (3.0) | Systematic Assessment | A gastrostomy tube (also called a G-tube) is a tube inserted through the abdomen that delivers nutrition directly to the stomach. One patient was hospitalized because the G-tube stopped working properly. |
|
| G-tube placement | General disorders | CTCAE (3.0) | Systematic Assessment | A gastrostomy tube (also called a G-tube) is a tube inserted through the abdomen that delivers nutrition directly to the stomach. Two patients were hospitalized because their gastrointestinal function declined and warranted G-tube placement. |
|
| GI bleeding | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment | Gastrointestinal (GI) bleeding refers to any bleeding that starts in the gastrointestinal tract. |
|
| Headache | General disorders | CTCAE (3.0) | Systematic Assessment | A headache or cephalalgia is pain anywhere in the region of the head or neck. |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment | "Hypoxia, or hypoxiation, is apathological condition in which the body as a whole (generalized hypoxia) or a region of the body (tissue hypoxia, or less commonly regional hypoxia) is deprived of adequate oxygen supply. " |
|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment | Nausea is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. |
|
| Neck bleeding | General disorders | CTCAE (3.0) | Systematic Assessment | Bleeding from neck region |
|
| Pain | General disorders | CTCAE (3.0) | Systematic Assessment | Patient experienced pain at grades 4 or higher. |
|
| Pericardial effusion | Cardiac disorders | CTCAE (3.0) | Systematic Assessment | "Pericardial effusion (""fluid around the heart"") is an abnormal accumulation of fluid in the pericardial cavity." |
|
| Pleurodesis | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment | Pleurodesis is a procedure used to cause the layers of the lung lining (the pleura) to stick together. |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment | Pneumonia is an inflammatorycondition of the lungaffecting primarily the microscopic air sacs known as alveoli. |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment | "Respiratory distress is a medical term that refers to both difficulty in breathing, and to the psychological experience associated with such difficulty, even if there is no physiological basis for experiencing such distress." |
|
| Retroperitoneal bleed | General disorders | CTCAE (3.0) | Systematic Assessment | "Bleeding in the retroperitoneal space (retroperitoneum), i.e. the anatomical space in the abdominal cavity behind (retro) the peritoneum." |
|
| Sepsis | Infections and infestations | CTCAE (3.0) | Systematic Assessment | Sepsis is a potentially deadly medical condition characterized by a whole-body inflammatory state (called a systemic inflammatory response syndrome or SIRS) caused by severe infection. |
|
| Stridor | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment | Stridor is a high-pitched wheezing sound resulting fromturbulent air flow in the upper airway. |
|
| Subacute hemorrhage of thalamus | General disorders | CTCAE (3.0) | Systematic Assessment | Subacute (between chronic and acute) hemorrhagic bleeding into the thalamus |
|
| Tracheitis | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment | Bacterial tracheitis is a bacterial infection of the trachea and is capable of producing airway obstruction. |
|
| Unresponsiveness | General disorders | CTCAE (3.0) | Systematic Assessment | Poor response or total loss of response to questions or other stimuli |
|
| Urinary tract infection | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment | A urinary tract infection (UTI) (also known as acute cystitis or bladder infection) is an infection that affects part of the urinary tract. |
|
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment | Vomiting (known medically as emesis and informally as throwing up and numerous other terms) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. |
|
|
| Dysphagia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment | Dysphagia is the medical term for the symptom of difficulty in swallowing. |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment | Shortness of breath |
|
| Epistaxis | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment | Nosebleed |
|
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment | "Fatigue (also called exhaustion, tiredness, lethargy, languidness, languor, lassitude, and listlessness) is a subjective feeling of tiredness which is distinct from weakness, and has a gradual onset." |
|
| Rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Xerostomia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment | Xerostomia is the medical term for the subjective symptom of dryness in the mouth. |
|
Not provided
Not provided
Not provided