Nab-Paclitaxel, Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Recurrent Head and Neck Cancer
Study Details
Study Description
Brief Summary
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cetuximab and cisplatin together with radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving cetuximab and cisplatin together with radiation therapy works in treating patients with recurrent head and neck cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
OBJECTIVES:
Primary
- To evaluate whether treatment with cetuximab, cisplatin, and intensity-modulated radiotherapy improves the overall survival of patients with recurrent squamous cell carcinoma of the head and neck.
Secondary
-
To determine the progression-free survival and local-regional progression in these patients.
-
To identify and estimate the incidence rate of acute and late toxicities associated with this treatment regimen.
-
To determine the pattern of disease progression in these patients.
OUTLINE: This is a multicenter study.
Patients receive cetuximab IV over 60-120 minutes once weekly in weeks 1-7. Patients also receive cisplatin IV over 60 minutes once weekly and undergo intensity-modulated radiotherapy once daily 5 days a week in weeks 2-7.
After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 4 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Single Arm: Chemotherapy with Concurrent Radiation therapy Nab-Paclitaxel, Cetuximab, Cisplatin, and Radiation Therapy intensity-modulated radiation therapy |
Drug: cetuximab
cetuximab
Other Names:
Drug: cisplatin
cisplatin
Other Names:
Radiation: intensity-modulated radiation therapy
IMRT
Other Names:
Drug: Nab-Paclitaxel
Nab-Paclitaxel
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) [2 year from the date of enrollment]
The 2-year PFS was measured from the date of enrollment to the first occurrence of new metastatic lesions, objective tumor progression, or death. The combination of cisplatin and cetuximab concurrent with radiation therapy for head and neck cancer has shown to have a favorable PFS. Patients were followed until death or from 7.5 months to 63.6 months (median 25.6 months) in those alive at last evaluation.
Secondary Outcome Measures
- Number of Participants With Acute and Late Toxicities [6 months within the end of treatment]
Incidence rate of acute and late toxicities of grade 3 or higher was measured after each treatment cycle was over. The most common late toxicities defined as toxicity occurring more than 90 days after treatment included laryngeal edema and xerostomia.
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
-
Pathologically confirmed squamous cell carcinoma (SCC) of the upper aerodigestive tract
-
Recurrent disease or second primary SCC
-
Recurrence or second primary must be confined to the head and neck above the clavicles (loco-regional recurrence)
-
Majority (≥ 75%) of the recurrent tumor must be in areas previously irradiated to ≥ 45 Gy
-
More than one recurrence allowed provided the first recurrence occurred > 6 months after the completion of prior radiotherapy
-
Unresectable disease OR has high-risk features after resection (e.g., positive margins and/or extracapsular extension)
-
No signs of carotid exposure
-
No primary nasopharyngeal or salivary gland tumor
-
Equivocal pulmonary nodes on chest CT scan allowed provided they are < 1 cm, cannot be safely biopsied, or are negative on PET scan
-
No distant metastasis
PATIENT CHARACTERISTICS:
-
Karnofsky performance status 70-100%
-
ANC ≥ 2,000/mm^3
-
Platelet count ≥ 100,000/mm^3
-
Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed)
-
Bilirubin < 1.5 mg/dL
-
AST or ALT < 2 times upper limit of normal
-
Creatinine clearance ≥ 50 mL/min
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception
-
Able to submit prior radiotherapy records to assure that the spinal cord tolerance is not exceeded
-
No active cardiac disease, including any of the following:
-
Unstable angina
-
Uncontrolled hypertension
-
Myocardial infarction within the past 6 months (unless successfully treated with coronary artery bypass graft or percutaneous transluminal coronary angioplasty)
-
Uncontrolled arrhythmia
-
Congestive heart failure
-
At least 3 heart-related hospitalizations within the past year
-
No severe chronic obstructive pulmonary disease requiring ≥ 3 hospitalizations within the past year
-
No concurrent medical illness that would impair patient tolerance to therapy or limit survival
-
No other invasive malignancy within the past 2 years
-
No pre-existing peripheral sensory neuropathy ≥ grade 2
-
No prior severe infusion reaction to a monoclonal antibody
-
No prisoners or individuals who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
PRIOR CONCURRENT THERAPY:
-
See Disease Characteristics
-
Recovered from prior surgery
-
Prior cisplatin and cetuximab allowed
-
At least 6 months since prior radiotherapy or chemotherapy
-
No prior radiotherapy > 75 Gy
-
No prior chemotherapy for recurrent head and neck cancer
-
Prior chemotherapy as a component of the primary treatment allowed
-
No prior combination cisplatin, cetuximab, and radiotherapy for recurrent head and neck cancer
-
Patients with a new primary head and neck cancer whose prior primary head and neck cancer was treated with concurrent cisplatin, cetuximab, and radiotherapy are eligible provided it has been > 6 months since treatment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospitals of Cleveland | Cleveland | Ohio | United States | 44106 |
| 2 | Baylor Research Institute | Dallas | Texas | United States | 75204 |
| 3 | University of Texas Southwestern Medical Center - Dallas | Dallas | Texas | United States | 75390 |
| 4 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- University of Texas Southwestern Medical Center
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CDR0000632295
- SCCC-04308
- CA 225314
- 112008-004
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Single Arm: Chemotherapy With Concurrent Radiation Therapy |
|---|---|
| Arm/Group Description | Nab-Paclitaxel, Cetuximab, Cisplatin, and Intensity-modulated radiation therapy (IMRT) |
| Period Title: Overall Study | |
| STARTED | 37 |
| COMPLETED | 33 |
| NOT COMPLETED | 4 |
Baseline Characteristics
| Arm/Group Title | Single Arm: Chemotherapy With Concurrent Radiation Therapy |
|---|---|
| Arm/Group Description | Nab-Paclitaxel, Cetuximab, Cisplatin, and Intensity-modulated radiation therapy (IMRT) |
| Overall Participants | 34 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
55.5
|
| Sex: Female, Male (Count of Participants) | |
| Female |
12
35.3%
|
| Male |
21
61.8%
|
| Region of Enrollment (participants) [Number] | |
| United States |
33
97.1%
|
Outcome Measures
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | The 2-year PFS was measured from the date of enrollment to the first occurrence of new metastatic lesions, objective tumor progression, or death. The combination of cisplatin and cetuximab concurrent with radiation therapy for head and neck cancer has shown to have a favorable PFS. Patients were followed until death or from 7.5 months to 63.6 months (median 25.6 months) in those alive at last evaluation. |
| Time Frame | 2 year from the date of enrollment |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Single Arm: Chemotherapy With Concurrent Radiation Therapy |
|---|---|
| Arm/Group Description | Nab-Paclitaxel, Cetuximab, Cisplatin, and Intensity-modulated radiation therapy (IMRT) |
| Measure Participants | 33 |
| Number (95% Confidence Interval) [percentage of participants] |
60
176.5%
|
| Title | Number of Participants With Acute and Late Toxicities |
|---|---|
| Description | Incidence rate of acute and late toxicities of grade 3 or higher was measured after each treatment cycle was over. The most common late toxicities defined as toxicity occurring more than 90 days after treatment included laryngeal edema and xerostomia. |
| Time Frame | 6 months within the end of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Single Arm: Chemotherapy With Concurrent Radiation Therapy |
|---|---|
| Arm/Group Description | Nab-Paclitaxel, Cetuximab, Cisplatin, and Intensity-modulated radiation therapy (IMRT) |
| Measure Participants | 33 |
| Count of Participants [Participants] |
21
61.8%
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Single Arm: Chemotherapy With Concurrent Radiation Therapy | |
| Arm/Group Description | Nab-Paclitaxel, Cetuximab, Cisplatin, and Intensity-modulated radiation therapy (IMRT) | |
All Cause Mortality |
||
| Single Arm: Chemotherapy With Concurrent Radiation Therapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/33 (0%) | |
Serious Adverse Events |
||
| Single Arm: Chemotherapy With Concurrent Radiation Therapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 21/33 (63.6%) | |
| Blood and lymphatic system disorders | ||
| Lymphopenia | 21/33 (63.6%) | 21 |
| Leukopenia | 3/33 (9.1%) | 3 |
| Neutropenia | 4/33 (12.1%) | 4 |
| Anemia | 3/33 (9.1%) | 3 |
| Infections and infestations | ||
| Infection | 7/33 (21.2%) | 7 |
| Injury, poisoning and procedural complications | ||
| Dermatitis | 6/33 (18.2%) | 6 |
Other (Not Including Serious) Adverse Events |
||
| Single Arm: Chemotherapy With Concurrent Radiation Therapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 10/33 (30.3%) | |
| Blood and lymphatic system disorders | ||
| Other electrolyte abnormalities | 8/33 (24.2%) | 8 |
| Hypophosphatemia | 3/33 (9.1%) | 3 |
| Gastrointestinal disorders | ||
| Dysphagia | 8/33 (24.2%) | 8 |
| Mucositis | 5/33 (15.2%) | 5 |
| General disorders | ||
| Anorexia | 5/33 (15.2%) | 5 |
| pain | 10/33 (30.3%) | 10 |
| Fatigue | 3/33 (9.1%) | 3 |
| Hyponatremia | 3/33 (9.1%) | 3 |
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Dr. Lucien Nedzi |
|---|---|
| Organization | UT Southwestern Medical Center |
| Phone | 214-645-7653 |
| lucien.nedzi@utsouthwestern.edu |
- CDR0000632295
- SCCC-04308
- CA 225314
- 112008-004