Recruiting
Phase 1

d-Limonene, Radiation, Platinum Based Chemo

Sponsor:

Stanford University

Code:

NCT04392622

Conditions

Xerostomia

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

D-Limonene Gelcaps

Intensity modulated radiotherapy (IMRT)

Cisplatin

Xerostomia questionnaire

Study Details

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.

Conditions

Xerostomia

Study ID

NCT04392622

Start date

Feb 15, 2021

Status verified date

Jul, 2026

Completion date

May 15, 2028

Anticipated

Primary completion date

Aug 15, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

40 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Supportive Care

Interventions and Outcome Measures

Arms

experimental: d-limonene -2gram

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

experimental: d-limonene -4gram

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

experimental: d-limonene -6gram

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

experimental: d-limonene -8gram

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

experimental: de-escalation dose d-limonene -6gram

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

experimental: de-escalation dose d-limonene -4gram

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

experimental: de-escalation dose d-limonene -2gram

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

Interventions

D-Limonene Gelcaps

Administered orally at 2 to 8 grams daily

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.

Cisplatin

Standard of Care -Cisplatin as 100 mg/m2 IV

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

Primary outcome measure

  • Dose limiting Toxicity [ Time Frame: 9 weeks ]

Central Contacts and Locations

Central contacts

Camellia Djebroun

650-736-5564cdjebrou@stanford.edu

Kelly Huang

650-724-4606kelhuang@stanford.edu

Locations

Stanford University

Recruiting

Stanford, California, United States, 94305

Contacts

Camellia Djebroun

650-736-5564cdjebrou@stanford.edu

Kelly Huang

650-724-4606kelhuang@stanford.edu

Principal Investigator:

Quynh-Thu Le, M.D.

More Information

Sponsor

Stanford University

Last update posted

Jul 28, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Stanford University on 2026-07-28.