Back to resultsd-Limonene +Radiation +Platinum Based Chemo for Xerostomia Prevention in Locally Advanced Head and Neck Squamous Cell Carcinoma
Primary Purpose
Xerostomia
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
D-Limonene Gelcaps
Intensity modulated radiotherapy (IMRT)
Cisplatin
Xerostomia questionnaire
Sponsored by
About this trial
This is an interventional supportive care trial for Xerostomia
Eligibility Criteria
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
Sites / Locations
- Stanford UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
d-limonene -2gram
d-limonene -4gram
d-limonene -6gram
d-limonene -8gram
de-escalation dose d-limonene -6gram
de-escalation dose d-limonene -4gram
de-escalation dose d-limonene -2gram
Arm Description
2 gram d-limonene orally, once daily delivered during chemoradiation
4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
8 gram d-limonene orally, as 4 grams 2 times daily delivered during chemoradiation
6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
2 gram d-limonene orally, once daily delivered during chemoradiation
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT04392622
First Posted
May 11, 2020
Last Updated
August 14, 2023
Sponsor
Stanford University
Collaborators
National Institutes of Health (NIH)
1. Study Identification
Unique Protocol Identification Number
NCT04392622
Brief Title
d-Limonene +Radiation +Platinum Based Chemo for Xerostomia Prevention in Locally Advanced Head and Neck Squamous Cell Carcinoma
Official Title
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 Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 15, 2021 (Actual)
Primary Completion Date
February 15, 2026 (Anticipated)
Study Completion Date
February 15, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stanford University
Collaborators
National Institutes of Health (NIH)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Xerostomia
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
d-limonene -2gram
Arm Type
Experimental
Arm Description
2 gram d-limonene orally, once daily delivered during chemoradiation
Arm Title
d-limonene -4gram
Arm Type
Experimental
Arm Description
4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
Arm Title
d-limonene -6gram
Arm Type
Experimental
Arm Description
6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
Arm Title
d-limonene -8gram
Arm Type
Experimental
Arm Description
8 gram d-limonene orally, as 4 grams 2 times daily delivered during chemoradiation
Arm Title
de-escalation dose d-limonene -6gram
Arm Type
Experimental
Arm Description
6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation
Arm Title
de-escalation dose d-limonene -4gram
Arm Type
Experimental
Arm Description
4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation
Arm Title
de-escalation dose d-limonene -2gram
Arm Type
Experimental
Arm Description
2 gram d-limonene orally, once daily delivered during chemoradiation
Intervention Type
Drug
Intervention Name(s)
D-Limonene Gelcaps
Intervention Description
Administered orally at 2 to 8 grams daily
Intervention Type
Radiation
Intervention Name(s)
Intensity modulated radiotherapy (IMRT)
Intervention Description
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
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Standard of Care -Cisplatin as 100 mg/m2 IV
Intervention Type
Other
Intervention Name(s)
Xerostomia questionnaire
Intervention Description
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 Information:
Title
Dose limiting Toxicity
Description
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).
Time Frame
9 weeks
Secondary Outcome Measure Information:
Title
Feasibility of adjuvant d-limonene administration
Description
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.
Time Frame
4 months
Title
Xerostomia toxicity
Description
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.
Time Frame
12 months post completion of chemoradiation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mahjabin Noroozi
Phone
650-721-4069
Email
mnoroozi@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Quynh-Thu Le
Organizational Affiliation
Stanford Universiy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mahjabin Noroozi
Phone
650-721-4069
Email
mnoroozi@stanford.edu
First Name & Middle Initial & Last Name & Degree
Quynh-Thu Le, M.D.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
d-Limonene +Radiation +Platinum Based Chemo for Xerostomia Prevention in Locally Advanced Head and Neck Squamous Cell Carcinoma
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