- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04392622
d-Limonene +Radiation +Platinum Based Chemo for Xerostomia Prevention in Locally Advanced Head and Neck Squamous Cell Carcinoma
A Phase 1 Study of d Limonene With Concurrent Radiation and Platinum Based Chemotherapy for Xerostomia Prevention in Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)
Study Overview
Status
Conditions
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 Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Mahjabin Noroozi
- Phone Number: 650-721-4069
- Email: mnoroozi@stanford.edu
Study Locations
-
-
California
-
Stanford, California, United States, 94305
- Recruiting
- Stanford University
-
Principal Investigator:
- Quynh-Thu Le, M.D.
-
Contact:
- Mahjabin Noroozi
- Phone Number: 650-721-4069
- Email: mnoroozi@stanford.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: d-limonene -2gram
2 gram d-limonene orally, once daily delivered during chemoradiation
|
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
|
Experimental: d-limonene -4gram
4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
|
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
|
Experimental: d-limonene -6gram
6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
|
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
|
Experimental: d-limonene -8gram
8 gram d-limonene orally, as 4 grams 2 times daily delivered during chemoradiation
|
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
|
Experimental: de-escalation dose d-limonene -6gram
6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
|
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
|
Experimental: de-escalation dose d-limonene -4gram
4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
|
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
|
Experimental: de-escalation dose d-limonene -2gram
2 gram d-limonene orally, once daily delivered during chemoradiation
|
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose limiting Toxicity
Time Frame: 9 weeks
|
Dose limiting toxicity is defined as d-limonene related toxicity causing:
|
9 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Feasibility of adjuvant d-limonene administration
Time Frame: 4 months
|
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.
|
4 months
|
Xerostomia toxicity
Time Frame: 12 months post completion of chemoradiation
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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.
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12 months post completion of chemoradiation
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Quynh-Thu Le, Stanford Universiy
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Head and Neck Neoplasms
- Stomatognathic Diseases
- Mouth Diseases
- Neoplasms, Squamous Cell
- Salivary Gland Diseases
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Xerostomia
- Antineoplastic Agents
- Cisplatin
Other Study ID Numbers
- IRB-51656 (Other Identifier: Stanford IRB)
- ENT0072 (Other Identifier: OnCore)
- 1P01CA257907-01A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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