This study explores the safety of d-limonene, a commercially-available dietary supplement (food) as a potential therapeutic for the severe dry mouth (xerostomia) experienced by patients with head and neck cancer as a side effect of their anti-cancer treatment.
Primary Objective:To determine the maximum tolerated dose (MTD) of d limonene when combined with radiation and platinum based chemotherapy in subjects with loco regionally advanced head and neck squamous cell carcinoma (HNSCC) based upon dose limiting toxicity (DLT) Secondary Objective: * To evaluate the feasibility and subject compliance with adjuvant administration of d limonene daily up to a maximum of 4 months after completion of chemoradiation * To correlate the level of d-limonene measured in the plasma to the dose levels(s) administered to the subject * To correlate the level of d limonene measured in the plasma to saliva flow rate and xerostomia questionnaire scores in subjects enrolled in this trial
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
40
Administered orally at 2 to 8 grams daily
Standard of Care -All patients will receive standard radiation treatment of 66 to 70 Gy given in 33 to 35 fractions (2 to 2.12 Gy/fractions) over 6.5 to 7 weeks.
Standard of Care -Cisplatin as 100 mg/m2 IV
Stanford University
Stanford, California, United States
RECRUITINGDose limiting Toxicity
Dose limiting toxicity is defined as d-limonene related toxicity causing: * Greater than 1 week delay in completing the radiation course. * Inability to receive ≥ 66 Gy of radiotherapy. * Inability to receive at least 200 mg/m2 of total cisplatin equivalent dose or a total area under the curve (AUC) of 10 for carboplatin equivalent dose due to toxicity related to d-limonene Grade 3 or higher diarrhea that is attributable to the study drug. * Grade 3 abdominal pain that is attributable to the study drug. The outcome will be reported as the number of participants per dose level who experience any DLT (a number without dispersion / variance).
Time frame: 9 weeks
Feasibility of adjuvant d-limonene administration
Participant compliance with adjuvant administration of d-limonene will be assessed as completing at least 14 weeks of per protocol adjuvant d-limonene treatment. The outcome is reported as the number of participants per dose level that were compliant.
Time frame: 4 months
Xerostomia toxicity
The degree of xerostomia will be assessed by the xerostomia survey. The survey consists of 8 items: 4 items regarding dryness or discomfort while eating or chewing and 4 items regarding dryness and discomfort while not eating or chewing. The participant will rate each item on a Likert scale from 0 to 10 (least effect to most severe effect) with higher scores implying greater dryness or discomfort. A summary score is calculated by summing the scores for each item and linearly transforming the score to produce a final score on a scale from 0 to 100. The outcome is reported as the mean and standard deviation of the final transformed scores from all subjects with survey results, by treatment level.
Time frame: 12 months post completion of chemoradiation
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Xerostomia questionnaire consists of 4 items on dryness while eating/speaking and 4 on dryness at rest. Patients rate each symptom on an 11 point ordinal Likert scale from 0 to 10, with higher scores indicating greater xerostomia