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

Stanford University

Status and phase: Enrolling; Phase 1

Conditions: Xerostomia

Treatments: Radiation: Intensity modulated radiotherapy (IMRT); Other: Xerostomia questionnaire; Drug: D-Limonene Gelcaps; Drug: Cisplatin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04392622

NCI-2021-03256 (Registry Identifier)

IRB-51656 (Other Identifier)

1P01CA257907-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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40 participants in 7 patient groups

d-limonene -2gram

Experimental group

Description:

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

Treatment:

Drug: Cisplatin

Other: Xerostomia questionnaire

Drug: D-Limonene Gelcaps

Radiation: Intensity modulated radiotherapy (IMRT)

d-limonene -4gram

Experimental group

Description:

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

Treatment:

Drug: Cisplatin

Other: Xerostomia questionnaire

Drug: D-Limonene Gelcaps

Radiation: Intensity modulated radiotherapy (IMRT)

d-limonene -6gram

Experimental group

Description:

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

Treatment:

Drug: Cisplatin

Other: Xerostomia questionnaire

Drug: D-Limonene Gelcaps

Radiation: Intensity modulated radiotherapy (IMRT)

d-limonene -8gram

Experimental group

Description:

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

Treatment:

Drug: Cisplatin

Other: Xerostomia questionnaire

Drug: D-Limonene Gelcaps

Radiation: Intensity modulated radiotherapy (IMRT)

de-escalation dose d-limonene -6gram

Experimental group

Description:

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

Treatment:

Drug: Cisplatin

Other: Xerostomia questionnaire

Drug: D-Limonene Gelcaps

Radiation: Intensity modulated radiotherapy (IMRT)

de-escalation dose d-limonene -4gram

Experimental group

Description:

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

Treatment:

Drug: Cisplatin

Other: Xerostomia questionnaire

Drug: D-Limonene Gelcaps

Radiation: Intensity modulated radiotherapy (IMRT)

de-escalation dose d-limonene -2gram

Experimental group

Description:

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

Treatment:

Drug: Cisplatin

Other: Xerostomia questionnaire

Drug: D-Limonene Gelcaps

Radiation: Intensity modulated radiotherapy (IMRT)