d-Limonene +Radiation +PlatinumBasedChemo for Xerostomia Prevention in LocallyAdvanced HNSCC
A Phase I Study of d-Limonene With Concurrent Radiation and Platinum Based Chemotherapy for Xerostomia Prevention in Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)
3 other identifiers
interventional
40
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2021
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 11, 2020
CompletedFirst Posted
Study publicly available on registry
May 19, 2020
CompletedStudy Start
First participant enrolled
February 15, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 15, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 15, 2028
July 20, 2025
July 1, 2025
6.5 years
May 11, 2020
July 16, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Dose 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).
9 weeks
Secondary Outcomes (2)
Feasibility of adjuvant d-limonene administration
4 months
Xerostomia toxicity
12 months post completion of chemoradiation
Study Arms (7)
d-limonene -2gram
EXPERIMENTAL2 gram d-limonene orally, once daily delivered during chemoradiation
d-limonene -4gram
EXPERIMENTAL4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
d-limonene -6gram
EXPERIMENTAL6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
d-limonene -8gram
EXPERIMENTAL8 gram d-limonene orally, as 4 grams 2 times daily delivered during chemoradiation
de-escalation dose d-limonene -6gram
EXPERIMENTAL6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
de-escalation dose d-limonene -4gram
EXPERIMENTAL4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
de-escalation dose d-limonene -2gram
EXPERIMENTAL2 gram d-limonene orally, once daily delivered during chemoradiation
Interventions
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
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
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- History of allergic reactions attributed to citrus fruits
- Pregnant or lactating
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Stanford Universitylead
- National Institutes of Health (NIH)collaborator
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Stanford University
Stanford, California, 94305, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Quynh-Thu Le
Stanford Universiy
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- SUPPORTIVE CARE
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 11, 2020
First Posted
May 19, 2020
Study Start
February 15, 2021
Primary Completion (Estimated)
August 15, 2027
Study Completion (Estimated)
May 15, 2028
Last Updated
July 20, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will not share