XerostomiaPhase 1NCT04392622
d-Limonene +Radiation +PlatinumBasedChemo for Xerostomia Prevention in LocallyAdvanced HNSCC
A Phase 1 study testing D-Limonene Gelcaps, Intensity modulated radiotherapy (IMRT) and Cisplatin in people with Xerostomia, run by Stanford University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Xerostomia
- What is being tested?
- D-Limonene Gelcaps, Intensity modulated radiotherapy (IMRT) and Cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2021to 15 May 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- History of allergic reactions attributed to citrus fruits
- Pregnant or lactating
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Stanford University
Stanford, California, 94305
Camellia Djebroun, 650-736-5564, cdjebrou@stanford.edu
Kelly Huang, 650-724-4606, kelhuang@stanford.edu
About this study
Official title: 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)
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.
Read the 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
- Conditions
- Xerostomia
- Being tested
- D-Limonene Gelcaps, Intensity modulated radiotherapy (IMRT), Cisplatin, Xerostomia questionnaire
- Medical subject headings
- Xerostomia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-Limonene GelcapsDrug
Administered orally at 2 to 8 grams daily
Intensity modulated radiotherapy (IMRT)Radiation
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.
CisplatinDrug
Standard of Care -Cisplatin as 100 mg/m2 IV
Xerostomia questionnaireOther
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
| Study group | Role | What they receive |
|---|---|---|
| d-limonene -2gram | Experimental | 2 gram d-limonene orally, once daily delivered during chemoradiation Receives: Drug: D-Limonene Gelcaps; Radiation: Intensity modulated radiotherapy (IMRT); Drug: Cisplatin; Other: Xerostomia questionnaire |
| d-limonene -4gram | Experimental | 4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation Receives: Drug: D-Limonene Gelcaps; Radiation: Intensity modulated radiotherapy (IMRT); Drug: Cisplatin; Other: Xerostomia questionnaire |
| d-limonene -6gram | Experimental | 6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation Receives: Drug: D-Limonene Gelcaps; Radiation: Intensity modulated radiotherapy (IMRT); Drug: Cisplatin; Other: Xerostomia questionnaire |
| d-limonene -8gram | Experimental | 8 gram d-limonene orally, as 4 grams 2 times daily delivered during chemoradiation Receives: Drug: D-Limonene Gelcaps; Radiation: Intensity modulated radiotherapy (IMRT); Drug: Cisplatin; Other: Xerostomia questionnaire |
| de-escalation dose d-limonene -6gram | Experimental | 6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation Receives: Drug: D-Limonene Gelcaps; Radiation: Intensity modulated radiotherapy (IMRT); Drug: Cisplatin; Other: Xerostomia questionnaire |
| de-escalation dose d-limonene -4gram | Experimental | 4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation Receives: Drug: D-Limonene Gelcaps; Radiation: Intensity modulated radiotherapy (IMRT); Drug: Cisplatin; Other: Xerostomia questionnaire |
| de-escalation dose d-limonene -2gram | Experimental | 2 gram d-limonene orally, once daily delivered during chemoradiation Receives: Drug: D-Limonene Gelcaps; Radiation: Intensity modulated radiotherapy (IMRT); Drug: Cisplatin; Other: Xerostomia questionnaire |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 9 weeks
Secondary outcomes (2)
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.
Measured: 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.
Measured: 12 months post completion of chemoradiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2020
- Study start15 Feb 2021
- Primary completion15 Aug 2027 (estimated)
- Study completion15 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for XerostomiaStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Quynh-Thu Le, Principal investigator, Stanford Universiy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04392622
- Sponsor's protocol ID
- IRB-51656
- Other IDs
- 1P01CA257907-01A1, NCI-2021-03256
- Status last verified
- Jul 2026
- First submitted
- 11 May 2020
- Last updated
- 28 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT04392622
- Acronym / sponsor ID
- IRB-51656
- Conditions
- Xerostomia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Study start
- 15 Feb 2021 (actual)
- Primary completion
- 15 Aug 2027 (estimated)
- Study completion
- 15 May 2028 (estimated)
- First posted
- 19 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| d-limonene -2gram | Experimental | Drug: D-Limonene Gelcaps, Radiation: Intensity modulated radiotherapy (IMRT), Drug: Cisplatin, Other: Xerostomia questionnaire2 gram d-limonene orally, once daily delivered during chemoradiation |
| d-limonene -4gram | Experimental | Drug: D-Limonene Gelcaps, Radiation: Intensity modulated radiotherapy (IMRT), Drug: Cisplatin, Other: Xerostomia questionnaire4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation |
| d-limonene -6gram | Experimental | Drug: D-Limonene Gelcaps, Radiation: Intensity modulated radiotherapy (IMRT), Drug: Cisplatin, Other: Xerostomia questionnaire6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation |
| d-limonene -8gram | Experimental | Drug: D-Limonene Gelcaps, Radiation: Intensity modulated radiotherapy (IMRT), Drug: Cisplatin, Other: Xerostomia questionnaire8 gram d-limonene orally, as 4 grams 2 times daily delivered during chemoradiation |
| de-escalation dose d-limonene -6gram | Experimental | Drug: D-Limonene Gelcaps, Radiation: Intensity modulated radiotherapy (IMRT), Drug: Cisplatin, Other: Xerostomia questionnaire6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation |
| de-escalation dose d-limonene -4gram | Experimental | Drug: D-Limonene Gelcaps, Radiation: Intensity modulated radiotherapy (IMRT), Drug: Cisplatin, Other: Xerostomia questionnaire4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation |
| de-escalation dose d-limonene -2gram | Experimental | Drug: D-Limonene Gelcaps, Radiation: Intensity modulated radiotherapy (IMRT), Drug: Cisplatin, Other: Xerostomia questionnaire2 gram d-limonene orally, once daily delivered during chemoradiation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (2 listed)
- History of allergic reactions attributed to citrus fruits
- Pregnant or lactating
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D-Limonene GelcapsAdministered orally at 2 to 8 grams daily | Drug | d-limonene -2gram, d-limonene -4gram, d-limonene -6gram, d-limonene -8gram, de-escalation dose d-limonene -2gram, de-escalation dose d-limonene -4gram, de-escalation dose d-limonene -6gram |
| Intensity modulated radiotherapy (IMRT)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. | Radiation | d-limonene -2gram, d-limonene -4gram, d-limonene -6gram, d-limonene -8gram, de-escalation dose d-limonene -2gram, de-escalation dose d-limonene -4gram, de-escalation dose d-limonene -6gram |
| CisplatinStandard of Care -Cisplatin as 100 mg/m2 IV | Drug | d-limonene -2gram, d-limonene -4gram, d-limonene -6gram, d-limonene -8gram, de-escalation dose d-limonene -2gram, de-escalation dose d-limonene -4gram, de-escalation dose d-limonene -6gram |
| Xerostomia questionnaireXerostomia 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 | Other | d-limonene -2gram, d-limonene -4gram, d-limonene -6gram, d-limonene -8gram, de-escalation dose d-limonene -2gram, de-escalation dose d-limonene -4gram, de-escalation dose d-limonene -6gram |
Primary outcome
Dose limiting Toxicity
Time frame: 9 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).
2 secondary outcomes
Feasibility of adjuvant d-limonene administration
Time frame: 4 months
Xerostomia toxicity
Time frame: 12 months post completion of chemoradiation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Quynh-Thu Le principal investigator
Stanford Universiy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing D-Limonene Gelcaps, Intensity modulated radiotherapy (IMRT) and Cisplatin in people with Xerostomia, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Camellia Djebroun (650-736-5564, cdjebrou@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting Toxicity (time frame: 9 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2026.