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d-Limonene +Radiation +Platinum Based Chemo for Xerostomia Prevention in Locally Advanced Head and Neck Squamous Cell Carcinoma

Phase 1
Recruiting
Conditions
Xerostomia
Interventions
Drug: D-Limonene Gelcaps
Radiation: Intensity modulated radiotherapy (IMRT)
Drug: Cisplatin
Other: Xerostomia questionnaire
Registration Number
NCT04392622
Lead Sponsor
Stanford University
Brief Summary

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.

Detailed Description

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

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
40
Inclusion Criteria

  • Histologically or cytologically confirmed diagnosis of advanced loco regional squamous cell carcinoma of the nasopharynx (AJCC v8 Stage II IV); oropharynx (AJCC v8 Stage I III for HPV+ cancer, excluding T1 2N0; AJCC v8 Stage III IV for Human papillomavirus (HPV) negative cancer); larynx (AJCC v8 Stage III to IV); or hypopharynx (AJCC v8 Stage III to IV), scheduled to undergo chemoradiation. Patients with squamous cell carcinoma of the head and neck from an unknown primary site with involved nodes (N1 to 3) also qualify.

  • Scheduled to received definitive RT with concurrent platinum based chemotherapy at Stanford

  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1

  • Must be able to swallow d limonene gelcaps at the time of enrollment.

  • Adequate hepatic function within 2 weeks prior to registration defined as follows: Bilirubin ≤ 2 mg/dL; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 times the upper limit of normal

  • Adequate hematologic function within 2 weeks prior to registration defined as follows:

    • Absolute neutrophil count (ANC): ≥ 1,500/mm3
    • Platelets: ≥ 100,000/mm3
    • Hemoglobin: ≥ 8.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable).

  • Adequate renal function defined as follows:

Serum creatinine ≤ 1.5 mg/dL within 2 weeks prior to registration or creatinine clearance (CC) ≥ 50 mL/min within 2 weeks prior to registration determined by 24 hour collection or estimated by Cockcroft Gault formula:

CCr male = [(140 - age) x (wt in kg)] [(Serum Cr mg/dL) x (72)] CCr female = 0.85 x (CrCl male)

  • Negative serum pregnancy test within 2 weeks prior to registration and agreement to use a birth control method during the entire duration of d limonene treatment for women of childbearing potential
  • Ability to understand and the willingness to sign a written informed consent document
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Exclusion Criteria
  • History of allergic reactions attributed to citrus fruits
  • Pregnant or lactating
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
de-escalation dose d-limonene -4gramCisplatin4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
d-limonene -2gramD-Limonene Gelcaps2 gram d-limonene orally, once daily delivered during chemoradiation
d-limonene -2gramXerostomia questionnaire2 gram d-limonene orally, once daily delivered during chemoradiation
d-limonene -4gramD-Limonene Gelcaps4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
d-limonene -4gramIntensity modulated radiotherapy (IMRT)4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
d-limonene -4gramXerostomia questionnaire4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
d-limonene -6gramD-Limonene Gelcaps6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
d-limonene -6gramIntensity modulated radiotherapy (IMRT)6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
d-limonene -6gramXerostomia questionnaire6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
d-limonene -2gramIntensity modulated radiotherapy (IMRT)2 gram d-limonene orally, once daily delivered during chemoradiation
d-limonene -2gramCisplatin2 gram d-limonene orally, once daily delivered during chemoradiation
d-limonene -8gramIntensity modulated radiotherapy (IMRT)8 gram d-limonene orally, as 4 grams 2 times daily delivered during chemoradiation
d-limonene -8gramCisplatin8 gram d-limonene orally, as 4 grams 2 times daily delivered during chemoradiation
d-limonene -8gramXerostomia questionnaire8 gram d-limonene orally, as 4 grams 2 times daily delivered during chemoradiation
de-escalation dose d-limonene -6gramIntensity modulated radiotherapy (IMRT)6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
de-escalation dose d-limonene -6gramXerostomia questionnaire6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
de-escalation dose d-limonene -4gramD-Limonene Gelcaps4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
de-escalation dose d-limonene -4gramIntensity modulated radiotherapy (IMRT)4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
de-escalation dose d-limonene -4gramXerostomia questionnaire4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
de-escalation dose d-limonene -2gramD-Limonene Gelcaps2 gram d-limonene orally, once daily delivered during chemoradiation
de-escalation dose d-limonene -2gramIntensity modulated radiotherapy (IMRT)2 gram d-limonene orally, once daily delivered during chemoradiation
de-escalation dose d-limonene -2gramXerostomia questionnaire2 gram d-limonene orally, once daily delivered during chemoradiation
de-escalation dose d-limonene -6gramD-Limonene Gelcaps6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
d-limonene -8gramD-Limonene Gelcaps8 gram d-limonene orally, as 4 grams 2 times daily delivered during chemoradiation
d-limonene -4gramCisplatin4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
d-limonene -6gramCisplatin6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
de-escalation dose d-limonene -6gramCisplatin6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
de-escalation dose d-limonene -2gramCisplatin2 gram d-limonene orally, once daily delivered during chemoradiation
Primary Outcome Measures
NameTimeMethod
Dose limiting Toxicity9 weeks

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).

Secondary Outcome Measures
NameTimeMethod
Feasibility of adjuvant d-limonene administration4 months

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.

Xerostomia toxicity12 months post completion of chemoradiation

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.

Trial Locations

Locations (1)

Stanford University

🇺🇸

Stanford, California, United States

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