d-Limonene +Radiation +PlatinumBasedChemo for Xerostomia Prevention in LocallyAdvanced HNSCC

NCT ID: NCT04392622

Last Updated: 2025-07-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-15

Study Completion Date

2028-05-15

Brief Summary

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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

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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

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Xerostomia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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d-limonene -2gram

2 gram d-limonene orally, once daily delivered during chemoradiation

Group Type EXPERIMENTAL

D-Limonene Gelcaps

Intervention Type DRUG

Administered orally at 2 to 8 grams daily

Intensity modulated radiotherapy (IMRT)

Intervention Type 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.

Cisplatin

Intervention Type DRUG

Standard of Care -Cisplatin as 100 mg/m2 IV

Xerostomia questionnaire

Intervention Type OTHER

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

d-limonene -4gram

4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation

Group Type EXPERIMENTAL

D-Limonene Gelcaps

Intervention Type DRUG

Administered orally at 2 to 8 grams daily

Intensity modulated radiotherapy (IMRT)

Intervention Type 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.

Cisplatin

Intervention Type DRUG

Standard of Care -Cisplatin as 100 mg/m2 IV

Xerostomia questionnaire

Intervention Type OTHER

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

d-limonene -6gram

6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation

Group Type EXPERIMENTAL

D-Limonene Gelcaps

Intervention Type DRUG

Administered orally at 2 to 8 grams daily

Intensity modulated radiotherapy (IMRT)

Intervention Type 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.

Cisplatin

Intervention Type DRUG

Standard of Care -Cisplatin as 100 mg/m2 IV

Xerostomia questionnaire

Intervention Type OTHER

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

d-limonene -8gram

8 gram d-limonene orally, as 4 grams 2 times daily delivered during chemoradiation

Group Type EXPERIMENTAL

D-Limonene Gelcaps

Intervention Type DRUG

Administered orally at 2 to 8 grams daily

Intensity modulated radiotherapy (IMRT)

Intervention Type 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.

Cisplatin

Intervention Type DRUG

Standard of Care -Cisplatin as 100 mg/m2 IV

Xerostomia questionnaire

Intervention Type OTHER

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

de-escalation dose d-limonene -6gram

6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation

Group Type EXPERIMENTAL

D-Limonene Gelcaps

Intervention Type DRUG

Administered orally at 2 to 8 grams daily

Intensity modulated radiotherapy (IMRT)

Intervention Type 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.

Cisplatin

Intervention Type DRUG

Standard of Care -Cisplatin as 100 mg/m2 IV

Xerostomia questionnaire

Intervention Type OTHER

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

de-escalation dose d-limonene -4gram

4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation

Group Type EXPERIMENTAL

D-Limonene Gelcaps

Intervention Type DRUG

Administered orally at 2 to 8 grams daily

Intensity modulated radiotherapy (IMRT)

Intervention Type 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.

Cisplatin

Intervention Type DRUG

Standard of Care -Cisplatin as 100 mg/m2 IV

Xerostomia questionnaire

Intervention Type OTHER

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

de-escalation dose d-limonene -2gram

2 gram d-limonene orally, once daily delivered during chemoradiation

Group Type EXPERIMENTAL

D-Limonene Gelcaps

Intervention Type DRUG

Administered orally at 2 to 8 grams daily

Intensity modulated radiotherapy (IMRT)

Intervention Type 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.

Cisplatin

Intervention Type DRUG

Standard of Care -Cisplatin as 100 mg/m2 IV

Xerostomia questionnaire

Intervention Type OTHER

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

Interventions

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D-Limonene Gelcaps

Administered orally at 2 to 8 grams daily

Intervention Type DRUG

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.

Intervention Type RADIATION

Cisplatin

Standard of Care -Cisplatin as 100 mg/m2 IV

Intervention Type DRUG

Xerostomia questionnaire

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

Intervention Type OTHER

Eligibility Criteria

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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

Exclusion Criteria

* History of allergic reactions attributed to citrus fruits
* Pregnant or lactating
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Stanford University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Quynh-Thu Le

Role: PRINCIPAL_INVESTIGATOR

Stanford Universiy

Locations

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Stanford University

Stanford, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Camellia Djebroun

Role: CONTACT

650-736-5564

Kelly Huang

Role: CONTACT

650-724-4606

Facility Contacts

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Camellia Djebroun

Role: primary

650-736-5564

Kelly Huang

Role: backup

650-724-4606

Other Identifiers

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1P01CA257907-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2021-03256

Identifier Type: REGISTRY

Identifier Source: secondary_id

IRB-51656

Identifier Type: -

Identifier Source: org_study_id

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