Clinical trial NCT01545687: CD2 Lozenges in Preventing Acute Oral Mucositis in Patients With Head and Neck Cancer Receiving Radiotherapy and Chemotherapy
Official title: A Phase III, Randomized, Double-Blind Study of Lactobacillus Brevis CD2 Lozenges Versus Placebo in the Prevention of Acute Oral Mucositis (OM) in Patients With Head and Neck Cancer Receiving Concurrent Radiotherapy and Chemotherapy
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Head and Neck Cancer
Oral Complications of Radiation Therapy
Pain
Weight Changes
Keywords: pain
oral complications of radiation therapy
weight changes
recurrent squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the larynx
recurrent squamous cell carcinoma of the nasopharynx
recurrent squamous cell carcinoma of the oropharynx
recurrent verrucous carcinoma of the larynx
stage I squamous cell carcinoma of the hypopharynx
stage I squamous cell carcinoma of the larynx
stage I squamous cell carcinoma of the nasopharynx
stage I squamous cell carcinoma of the oropharynx
stage I verrucous carcinoma of the larynx
stage II squamous cell carcinoma of the hypopharynx
stage II squamous cell carcinoma of the larynx
stage II squamous cell carcinoma of the nasopharynx
stage II squamous cell carcinoma of the oropharynx
stage II verrucous carcinoma of the larynx
stage III squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage III squamous cell carcinoma of the nasopharynx
stage III squamous cell carcinoma of the oropharynx
stage III verrucous carcinoma of the larynx
stage IV squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the nasopharynx
stage IVA squamous cell carcinoma of the larynx
stage IVA squamous cell carcinoma of the oropharynx
stage IVA verrucous carcinoma of the larynx
stage IVB squamous cell carcinoma of the larynx
stage IVB squamous cell carcinoma of the oropharynx
stage IVB verrucous carcinoma of the larynx
stage IVC squamous cell carcinoma of the larynx
stage IVC squamous cell carcinoma of the oropharynx
stage IVC verrucous carcinoma of the larynx
stage I squamous cell carcinoma of the lip and oral cavity
stage I verrucous carcinoma of the oral cavity
stage II squamous cell carcinoma of the lip and oral cavity
stage II verrucous carcinoma of the oral cavity
stage III squamous cell carcinoma of the lip and oral cavity
stage III verrucous carcinoma of the oral cavity
stage IVA squamous cell carcinoma of the lip and oral cavity
stage IVA verrucous carcinoma of the oral cavity
stage IVB squamous cell carcinoma of the lip and oral cavity
stage IVB verrucous carcinoma of the oral cavity
stage IVC squamous cell carcinoma of the lip and oral cavity
stage IVC verrucous carcinoma of the oral cavity
recurrent squamous cell carcinoma of the lip and oral cavity
recurrent verrucous carcinoma of the oral cavity
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2012-03-07
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Lactobacillus bevis CD2 lozenge may help prevent symptoms of mucositis, or mouth sores, in patients receiving radiation therapy and chemotherapy. This therapy may improve the quality of life of patients with head and neck cancer.

PURPOSE: This phase III trial studies how well Lactobacillus bevis CD2 lozenge prevents oral mucositis in patients with head and neck cancer who are being treated with cisplatin and radiation therapy. These results will be compared to results in patients using placebo lozenges.

Detailed description: OBJECTIVES:

Primary

* To determine whether Lactobacillus brevis CD2 lozenges are effective in reducing oral mucositis (OM)-related pain in patients undergoing chemoradiotherapy (CRT) for head and neck squamous cell carcinoma, as measured by the area under the curve (AUC) of Mouth and Throat Soreness (MTS) score (Oral Mucositis Daily Questionnaire \[OMDQ\] question 2) measured daily during CRT and daily for 4 weeks after completion of CRT.

Secondary

* To assess whether L. brevis CD2 lozenges reduce OM as assessed by the provider using the WHO OM scale, Oral Mucositis Assessment Scale (OMAS), and Common Terminology Criteria Adverse Events (CTCAE).
* To assess whether L. brevis CD2 lozenges reduce the impact of OM on the ability to swallow, drink, eat, talk, and sleep, as assessed by the MTS-Activity Limitations (MTS-AL).
* To assess whether L. brevis CD2 lozenges improve quality of life, as assessed by the Functional Assessment of Cancer Therapy - Head and Neck (FACT-HN).
* To assess whether L. brevis CD2 lozenges reduce opioid requirements.
* To assess whether L. brevis CD2 lozenges improve radiotherapy compliance.
* To assess whether L. brevis CD2 lozenges reduce weight loss and the need for a feeding tube.
* To assess whether L. brevis CD2 lozenges affect disease-free survival (DFS) at 12 months after treatment.
* To evaluate the effect of L. brevis CD2 lozenges on salivary biomarkers, including metabonomic and inflammatory markers, as measured at baseline, week 3 of CRT, and during the last week of CRT. (exploratory)

OUTLINE: This is a multicenter, randomized, placebo-controlled, double-blind study. Patients are stratified according to primary disease site (oral cavity/oropharynx vs nasopharynx vs hypopharynx/larynx), context of chemoradiotherapy (CRT) (definitive vs post-operative), cisplatin schedule (every 3 weeks \[100 mg/m\^2\] vs every week \[30-40 mg/m\^2\]), and use of intensity-modulated radiotherapy (IMRT) (yes vs no). Patients are randomized to 1 of 2 treatment regimens.

* Arm I: Patients dissolve in mouth 1 lozenge of Lactobacillus brevis CD2 every 2-3 hours (total of 6 per day) daily during CRT (comprising cisplatin and radiotherapy \[RT\]) and for 4 weeks after, including weekends.
* Arm II: Patients dissolve in mouth 1 lozenge of placebo every 2-3 hours (total of 6 per day) daily during CRT and for 4 weeks after, including weekends.

Patients complete questionnaires about their quality of life and pain at baseline and daily during study treatment.

Saliva is collected from some patients before starting RT, during week 3 of RT, and during the last week of RT for NMR-spectroscopic metabolomic analysis and future cytokine analysis.

After completion of study treatment, patients are followed up at 12 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologic proof of squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx
* Planned course of definitive or post-operative radiotherapy (RT) to a total dose of ≥ 60 Gy using 1.8 to 2.0 Gy per fraction
* At least one third of the oral cavity mucosa must be included in the RT fields, as estimated by the treating radiation oncologist
* Planned concurrent administration of cisplatin chemotherapy (either 100 mg/m\^2 every 3 weeks or 30-40 mg/m\^2 every week)

PATIENT CHARACTERISTICS:

* ECOG performance status (PS) 0, 1, or 2
* Hemoglobin ≥ 10.0 g/dL
* White blood cell (WBC) ≥ 3,500 x10\^9/L
* Absolute neutrophil count (ANC) ≥ 1,500 x10\^9/L
* Platelet count ≥ 100,000 x10\^9/L
* Willing to abstain from ingestion of yogurt products and/or any product containing probiotics during study drug treatment
* Ability to complete questionnaire(s) by themselves or with assistance
* Willing to provide saliva samples for correlative research purposes (first 50 patients)
* Not pregnant or nursing
* Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential
* Men or women of childbearing potential must employ adequate contraception
* No co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
* No current untreated oral candidiasis, oral herpes simplex virus (HSV) infection, or oral mucositis

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No split-course RT planned
* No prior head and neck RT

Primary outcomes:
measure: The AUC of the MTS score
timeFrame: Up to 12 months
Secondary outcomes:
measure: OM measured by WHO OM scale, OMAS and CTCAE weekly during CRT
timeFrame: Up to 12 months
measure: Impact of OM on the ability to swallow, drink, eat, talk, and sleep, as assessed by the MTS-AL
timeFrame: Up to 12 months
measure: Quality of life as assessed by the FACT-HN
timeFrame: Up to 12 months
measure: Opioid requirement (frequency, morphine equivalent dose) as measured by daily OMDQ
timeFrame: Up to 12 months
measure: DFS at 12 months after treatment
timeFrame: at 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Mayo Clinic
name: Robert C. Miller, MD
role: PRINCIPAL_INVESTIGATOR
References: