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Trial record 57 of 1986 for:    oxaliplatin

Adjuvant Chemoradiation With Weekly Oxaliplatin in Resected Head and Neck Cancer

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ClinicalTrials.gov Identifier: NCT00256308
Recruitment Status : Terminated (Halted prematurely due to slow accrual)
First Posted : November 21, 2005
Results First Posted : May 1, 2018
Last Update Posted : May 1, 2018
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Sai-Hong Ignatius Ou, University of California, Irvine

Tracking Information
First Submitted Date  ICMJE November 17, 2005
First Posted Date  ICMJE November 21, 2005
Results First Submitted Date  ICMJE June 26, 2013
Results First Posted Date  ICMJE May 1, 2018
Last Update Posted Date May 1, 2018
Study Start Date  ICMJE February 2005
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2018)
Frequency and Severity of Toxicities [ Time Frame: 2 years ]
Study was terminated by funding source for slow accrual. Upon termination notification, the IRB closure was submitted and all research procedures stopped, inclusive of completing any analysis of data collected.
Original Primary Outcome Measures  ICMJE
 (submitted: November 17, 2005)
Assess the frequency and severity of toxicities
Change History Complete list of historical versions of study NCT00256308 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 27, 2018)
  • Locoregional Control Rate [ Time Frame: 2 years ]
    Study was terminated by funding source for slow accrual. Upon termination notification, the IRB closure was submitted and all research procedures stopped, inclusive of completing any analysis of data collected.
  • Disease-free Survival Rate [ Time Frame: 2 years ]
    Study was terminated by funding source for slow accrual. Upon termination notification, the IRB closure was submitted and all research procedures stopped, inclusive of completing any analysis of data collected. Progression-free survival: from date of registration to date of first observation of progressive disease, death due to any cause or symptomatic deterioration Progression: Appearance of any new lesion/site. The site of the new lesion will be recorded. Death due to disease without prior documentation of progression and without symptomatic deterioration Symptomatic deterioration: Global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. Efforts should be made to obtain objective evidence of progression after discontinuation
  • Overall Survival Rate [ Time Frame: 2 years ]
    Study was terminated by funding source for slow accrual. Upon termination notification, the IRB closure was submitted and all research procedures stopped, inclusive of completing any analysis of data collected. From date of registration to date of death due to any cause
  • Sites of Relapse [ Time Frame: 2 years ]
    Study was terminated by funding source for slow accrual. Upon termination notification, the IRB closure was submitted and all research procedures stopped, inclusive of completing any analysis of data collected.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2005)
Evaluate the 2 year locoregional control rate
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Adjuvant Chemoradiation With Weekly Oxaliplatin in Resected Head and Neck Cancer
Official Title  ICMJE A Phase II Study of Adjuvant Chemoradiation With Weekly Oxaliplatin in Patients With High Risk Resected Squamous Cell Carcinoma of the Head and Neck Region
Brief Summary

Oxaliplatin-containing regimens have been safely and successfully used in combination with concurrent radiation in treatment of solid tumors such as rectal and esophageal cancers. The Lyon R0-04 phase II trial utilized the combination of Oxaliplatin, infusional 5-fluorouracil (5-FU) and radiation in the treatment of rectal cancer. The trial showed a combined preoperative chemoradiotherapy and Oxaliplatin-containing regimen is well tolerated with no increase surgical toxicity. The good response rate observed warrants its use in further clinical trials.

The combination of oxaliplatin, 5-FU, and radiation also have been used in a Phase I/II trial in esophageal cancer. In this particular trial, eligibility included therapeutically naïve esophageal cancer subjects with clinical disease stages II to IV. Initial doses and schedules for cycle 1 consisted of Oxaliplatin 85 mg/m2 on days 1, 15, and 29; continuous infusion of 5-FU 180 mg/m2 for 24 hours for 35 days; and radiation therapy (RT) 1.8 Gy in 28 fractions starting on day 8. At completion of cycle 1, eligible subjects could undergo an operation or begin cycle 2 without RT. Postoperative subjects were eligible for cycle 2. Stage IV subjects were allowed three cycles in the absence of disease progression. 38 subjects were treated (22 stage IV, 16 stage II-III). 38 eligible subjects received therapy: 22 non-invasively staged as IV and 16 non-invasively staged as IV and 16 non-invasively staged as II and III. 36 subjects completed cycle 1, 29 subjects started cycle 2, and 24 subjects completed cycle 2. The combined-modality therapy was well tolerated, but dose limiting toxicity (DLT) prevented Oxaliplatin and 5-FU escalation. No grade 4 hematologic toxicity was noted. Eleven grade 3 and two grade 4 clinical toxicities were noted in eight subjects. After cycle 1, 29 subjects (81%) had no cancer in the esophageal mucosa. 13 subjects underwent an operation with intent to resect the esophagus and 5 subjects (38%) exhibited pathologic complete responses. There was no surgical mortality. Only 1 subject developed post-operative tracheoesphageal fistula. The results of these trials described above indicated that combination of oxaliplatin and radiation is safe and efficacious and dose not compromise surgical wound healing, repair and clinical outcome.

Detailed Description

Adjuvant treatment of resected head and neck cancers The incidence of locoregional failures and distant metastasis is high after primary resection of squamous cell carcinoma of the head and neck (HNSCC), especially in patients with unfavorable prognostic factors such as residual disease, histological evidence of extracapsular spread, and/or multiple neck nodes. RT is indicated as an adjuvant therapy to surgery. In the past 2 decades, RT was mainly delivered post-operatively, and the therapeutic gain with this combination is now well documented. Despite an overall 2-year freedom of recurrance of approximately of 70-75%, survival rates are usually poor in the whole HNSCC patient population, and they usually do not exceed 30 to 35% at 5 years. The incidence of metastases in locally advanced but resectable head and neck cancer can reach 15 to 20%. The role of systemic chemotherapy has been tested in clinical trials to determine if the addition of chemotherapy can decrease locoregional and distant failure and improve survival.

Oxaliplatin and radiation in solid tumors Oxalipaltin-containing regimens have been safely and successfully used in combination with concurrent radiation in treatment of solid tumors such as rectal and esophageal cancers. Results of previous trials indicated that combination of oxaliplatin and radiation is safe and efficacious and dose not compromise surgical wound healing, repair and clinical outcome.

Oxaliplatin and radiation in head and neck cancer Oxaliplatin and radiation has been used in a randomized phase II study comparing standard radiation with or without weekly oxaliplatin in the treatment of locally advanced nasopharyngeal carcinoma. Radiation was administered at 70-74 Gy to the primary tumor site, 60-64 Gy to the involved areas of the neck and 50 Gy to the uninvolved area of the neck. Chemotherapy with oxaliplatin at 70 mg/m2 was given weekly for 6 courses with standard radiation in the investigational arm. Interim results concurrent radiation with weekly oxaliplatin resulted in a higher complete response in the primary tumor site and in the cervical lymph nodes. There was no difference in the incidences of dry mouth, stomatitis, skin reaction, peripheral neuropathy or hematological toxicities between the 2 treatment arms. Patients receiving the concurrent radiation and oxaliplatin treatment did experience more gastrointestinal toxicities mostly nausea and vomiting. The only grade 3 toxicities are thrombocytopenia (5.1%), nausea/vomiting (12.8%) and skin reaction (25.6%).

Microscopically involved margins, involvement of two or more nodes, extracapusular spread, presence of perineural involvement, and vascular embolisms are associated with an approximately 25% to 30% probability of developing locoregional failure. The addition of cisplatin to radiation reduces the locoregional failure and distant metastasis. We propose to investigate the toxicities of using weekly oxaliplatin with radiation in the treatment of high risk resected head and neck patients since oxaliplatin has a better side effects profile. The high risk factors will be the same criteria utilized in both RTOG 9501 and EORTC 22931. They include microscopically involved margins, involvement of two or more nodes, extracapusular spread, presence of perineural involvement, vascular embolisms, and oral cavity or oropharyngeal carcinoma with lymph nodes metastasis at level IV or V.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Head and Neck Cancer
Intervention  ICMJE
  • Drug: Oxaliplatin
    70mg/m2 IV over 120 min once a week during radiation
    Other Name: Eloxatin
  • Procedure: Radiation
    200 cGy/day - Megavoltage equipment with energy of Cobalt 60 or higher - Daily from Monday to Friday
Study Arms  ICMJE Experimental: Oxaliplatin
Oxaliplatin-70mg/m2 IV over 120 min once a week during radiation. Radiation-200 centigray (cGy) per day - Megavoltage equipment with energy of Cobalt 60 or higher - Daily from Monday to Friday.
Interventions:
  • Drug: Oxaliplatin
  • Procedure: Radiation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 27, 2018)
6
Original Enrollment  ICMJE
 (submitted: November 17, 2005)
10
Actual Study Completion Date  ICMJE October 2011
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • All subjects must have histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the head and neck region. Primary tumor sites include: oral cavity, pharynx (oropharynx, hypopharynx), or larynx (supraglottis, glottis subglottis). Nasopharynx primary will be excluded.
  • The resected tumor must have one or more of the following high risk features: histologic extracapsular nodal extension involvement of ≥ 2 regional lymph nodes, mucosal margin of resection with invasive cancer (limited to microscopic detection only), tumor with perineural invasion, tumor with lymphovascular invasion, oral cavity and oropharynx carcinomas with positive lymph nodes metastasis at level IV or V.
  • Radiation must begin within 28 to 56 days after surgical resection.
  • All subjects must be 18 years of age or older.
  • Subjects must have a Zubrod performance of 0-2.

Exclusion Criteria:

  • Subjects must not have distant metastatic disease (M1).
  • Subjects must NOT have prior therapy with oxaliplatin.
  • Subjects with any evidence of active or uncontrolled infection, recent myocardial infection, unstable angina, or life-threatening arrhythmia are not eligible.
  • Patients with severe psychiatric disorder are not eligible.
  • No other prior malignancy is allowed except for adequately treated basal cell or squamous cell carcinoma, in situ cervical cancer, or adequately treated Stage I and II cancer from which the patient is in complete remission, or any other malignancy from which the patient has been disease-free for 5 years.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00256308
Other Study ID Numbers  ICMJE UCI 04-40
2004-3999 ( Other Identifier: University of California, Irvine )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sai-Hong Ignatius Ou, University of California, Irvine
Study Sponsor  ICMJE University of California, Irvine
Collaborators  ICMJE Sanofi
Investigators  ICMJE
Principal Investigator: Sai-Hong Ignatius Ou, MD, PhD Chao Family Comprehensive Cancer Center
PRS Account University of California, Irvine
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP