Back to resultsAlpha Lipoic Acid to Decrease Pain and Side Effects in Concurrent Treatment of HNSCC
Primary Purpose
HNSCC
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Alpha Lipoic Acid
Sponsored by
About this trial
This is an interventional supportive care trial for HNSCC
Eligibility Criteria
Inclusion Criteria:
- Provision to sign and date the consent form.
- Stated willingness to comply with all study procedures and be available for the duration of the study.
- Be a male or female aged 18-100.
- Histologically or cytologically confirmed stage II-IVB HNSCC of the oral cavity, hypopharynx, oropharynx, larynx, or nasopharynx.
- Ability to take medication orally or per feeding tube and be willing to adhere to the medication regimen.
- Patients who are deemed appropriate for definitive, adjuvant, or palliative radiation with total planned dose > 30 Gy.
Patients who are deemed appropriate for concurrent systemic therapy with radiation including cisplatin (100 mg/m2 triweekly or 30-40 mg/m2 weekly), carboplatin (AUC 1-2 weekly) +/- paclitaxel (30 mg/m2 weekly) or cetuximab (400 mg/m2 loading followed by 250 mg/m2 weekly.
a. The final 3 patients in the dose expansion group undergoing the PK/PD study must be deemed appropriate for cisplatin.
- For females of reproductive potential: use of highly effective contraception including hormonal contraceptives, intrauterine devices (IUD), vasectomy, tubal ligation, and double barrier methods (combination of male condom, female condom, cervical cap, diaphragm, contraceptive sponge).
- For males of reproductive potential: use of condoms.
- ECOG performance status ≤ 2.
Exclusion Criteria:
- Participation in another clinical study with an investigational product during the last 30 days.
- Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study, a clinical study not involving pharmaceutical or radiation techniques, or during the follow-up period of an interventional study.
- Women who are pregnant or lactating. Patients of reproductive potential must have a negative serum or urine pregnancy test within 72 hours of start of study drug.
- Patients who are currently taking gabapentin, pregabalin, amitriptyline, nortriptyline, or duloxetine.
- Known allergy or hyposensitivity to alpha lipoic acid.
- Judgement by the investigator that the patient is unsuitable to participate in the study and the patient in unlikely to comply with study procedures, restrictions, and requirements.
Sites / Locations
- Abigail E Berry
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Alpha Lipoic Acid (ALA) during chemoradiation
Arm Description
Stage II-IVB HNSCC patients receiving concurrent systemic therapy and radiation as standard of care will receive ALA before, during, and after treatment. The drug will have dose escalation in a 3+3 design. The first group of 3 patients will receive 600 mg twice a day. If there are no DLTs, the next 3 patients will receive the highest dose of 600 mg three times a day. If one or more patients develop a DLT at any of the dosing levels, the group will either be expanded or dropped to a lower dose level.
Outcomes
Primary Outcome Measures
MTD and RP2D of ALA during chemoradiotherapy for HNSCC patients
The maximum tolerated dose will be the highest dose in the planned schema that is given without evidence of SAEs.
The RP2D will incorporate the MTD and PKs to determine the dose that is best tolerated as well as has the concentration necessary to be effective according to historical studies.
Secondary Outcome Measures
Safety of ALA by following adverse events (AEs)
Adverse events will be documented to determine the primary endpoints as well as to categorize potential side effects that can be attributed to ALA. CTCAE version 5.0 will be used to categorize the AEs
Maximum plasma concentration of ALA at the MTD with chemoradiotherapy
Maximum plasma concentration will be evaluated on the 3 patients in the dose expansion group at the MTD. This will be studied when given with cisplatin for standardization to ensure concentration is similar to when ALA is given alone.
Change in Oral Mucositis Assessment Scale (OMAS) from baseline
OMAS scores will give preliminary measures on efficacy of drug to control pain and improve quality of life which will be the primary focus in future studies. Total scores will be collected from 0 (no mucositis) to 45 (worse mucositis). Average OMAS and change from baseline to worst score will be evaluated.
Change in Visual Assessment Score (VAS) for pain from baseline
VAS for pain will give preliminary measures on efficacy of drug to control pain which will be the primary focus in future studies. The VAS score is from 0-10 with 0 being no pain and 10 being the worse possible pain. Average VAS and change from baseline to worst score will be evaluated.
Change in quality of life measures using the Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN) during chemoradiation
The Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN) will be used to evaluate quality of life measures at baseline and during treatment. This scale has the sub-categories of physical well being, social/family well-being, emotional well-being, functional well-being, and additional concerns. Each question is scaled from 0 (worst) to 4 (best). Each sub-category will be totaled and a total FACT-HN score will be calculated for each time point. Average sub-category and total scores will be calculated as well as change from baseline to worst scores during treatment.
Total concurrent opioid use using patient reported diaries
Patients will document every dose of opioid medications taken during the study period. This will be used to used to calculated total opioid amounts taken (as oxycodone equivalents) as well as total duration of opioid use in days.
Progression free survival (PFS)
Progression free survival will be calculated as time to disease progression from start of treatment measured in weeks. This will be documented by PET/CT and/or CT neck and chest completed prior to start of treatment and approximately 3 and 6 months after treatment discontinuation
Overall survival (OS)
OS will be calculated as time from start of treatment to death as measured in weeks. This will be documented by survival follow-up during study visits
Full Information
NCT ID
NCT04042935
First Posted
July 26, 2019
Last Updated
August 31, 2023
Sponsor
University of Colorado, Denver
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT04042935
Brief Title
Alpha Lipoic Acid to Decrease Pain and Side Effects in Concurrent Treatment of HNSCC
Official Title
Alpha Lipoic Acid to Decrease Treatment Related Pain and Side Effects During Concurrent Chemoradiation in HNSCC
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
February 27, 2020 (Actual)
Primary Completion Date
February 19, 2021 (Actual)
Study Completion Date
September 24, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a phase I, single-center, non-randomized, 3+3 dose-escalation study of alpha lipoic acid given during chemotherapy-radiation in HNSCC patients with non-metastatic disease.
Detailed Description
The study will be completed when the MTD and RP2D are determined. This will be either when 2 or more patients have a DLT at a particular dose level, or when 6 patients have completed treatment at the highest dose level (600 mg TID). The final 3 patients enrolled at the highest tolerated dose will also complete PK studies.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HNSCC
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
3+3 Dose Escalation: Dose Level -2: ALA 300 mg daily Dose Level -1: ALA 600 mg daily Dose Level 1: ALA 600 mg BID Dose Level 2: ALA 600 mg TID
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Alpha Lipoic Acid (ALA) during chemoradiation
Arm Type
Experimental
Arm Description
Stage II-IVB HNSCC patients receiving concurrent systemic therapy and radiation as standard of care will receive ALA before, during, and after treatment. The drug will have dose escalation in a 3+3 design. The first group of 3 patients will receive 600 mg twice a day. If there are no DLTs, the next 3 patients will receive the highest dose of 600 mg three times a day. If one or more patients develop a DLT at any of the dosing levels, the group will either be expanded or dropped to a lower dose level.
Intervention Type
Drug
Intervention Name(s)
Alpha Lipoic Acid
Intervention Description
Stage II-IVB HNSCC patients receiving concurrent systemic therapy and radiation in the definitive, adjuvant, or palliative setting will receive ALA according to their prescribed dose level. ALA will be taken orally or per feeding tube. It will start 1 week prior to the start of CRT, continue on through CRT, and then continue for 2 weeks after the completion of CRT. Patients will be given dosing diaries to document date and time of each drug administration as well as any missed doses. They will also have weekly visits to report AEs and concurrent medications, have a history and physical exam, report VAS pain scores and OMAS scores, and fill FACT-HN surveys.
Primary Outcome Measure Information:
Title
MTD and RP2D of ALA during chemoradiotherapy for HNSCC patients
Description
The maximum tolerated dose will be the highest dose in the planned schema that is given without evidence of SAEs.
The RP2D will incorporate the MTD and PKs to determine the dose that is best tolerated as well as has the concentration necessary to be effective according to historical studies.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Safety of ALA by following adverse events (AEs)
Description
Adverse events will be documented to determine the primary endpoints as well as to categorize potential side effects that can be attributed to ALA. CTCAE version 5.0 will be used to categorize the AEs
Time Frame
up to 18 months
Title
Maximum plasma concentration of ALA at the MTD with chemoradiotherapy
Description
Maximum plasma concentration will be evaluated on the 3 patients in the dose expansion group at the MTD. This will be studied when given with cisplatin for standardization to ensure concentration is similar to when ALA is given alone.
Time Frame
At start of ALA, Day 1, and Day 15, for 3 dose expansion PK patients
Title
Change in Oral Mucositis Assessment Scale (OMAS) from baseline
Description
OMAS scores will give preliminary measures on efficacy of drug to control pain and improve quality of life which will be the primary focus in future studies. Total scores will be collected from 0 (no mucositis) to 45 (worse mucositis). Average OMAS and change from baseline to worst score will be evaluated.
Time Frame
From start of treatment to post-treatment surveillance scans, up to 6 months
Title
Change in Visual Assessment Score (VAS) for pain from baseline
Description
VAS for pain will give preliminary measures on efficacy of drug to control pain which will be the primary focus in future studies. The VAS score is from 0-10 with 0 being no pain and 10 being the worse possible pain. Average VAS and change from baseline to worst score will be evaluated.
Time Frame
From start of treatment to post-treatment surveillance scans, up to 6 months
Title
Change in quality of life measures using the Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN) during chemoradiation
Description
The Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN) will be used to evaluate quality of life measures at baseline and during treatment. This scale has the sub-categories of physical well being, social/family well-being, emotional well-being, functional well-being, and additional concerns. Each question is scaled from 0 (worst) to 4 (best). Each sub-category will be totaled and a total FACT-HN score will be calculated for each time point. Average sub-category and total scores will be calculated as well as change from baseline to worst scores during treatment.
Time Frame
From start of treatment to post-treatment surveillance scans, up to 6 months
Title
Total concurrent opioid use using patient reported diaries
Description
Patients will document every dose of opioid medications taken during the study period. This will be used to used to calculated total opioid amounts taken (as oxycodone equivalents) as well as total duration of opioid use in days.
Time Frame
From start of treatment to post-treatment surveillance scans, up to 6 months
Title
Progression free survival (PFS)
Description
Progression free survival will be calculated as time to disease progression from start of treatment measured in weeks. This will be documented by PET/CT and/or CT neck and chest completed prior to start of treatment and approximately 3 and 6 months after treatment discontinuation
Time Frame
Screening, 3 and 6 month follow up visits
Title
Overall survival (OS)
Description
OS will be calculated as time from start of treatment to death as measured in weeks. This will be documented by survival follow-up during study visits
Time Frame
From start of treatment up to 18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provision to sign and date the consent form.
Stated willingness to comply with all study procedures and be available for the duration of the study.
Be a male or female aged 18-100.
Histologically or cytologically confirmed stage II-IVB HNSCC of the oral cavity, hypopharynx, oropharynx, larynx, or nasopharynx.
Ability to take medication orally or per feeding tube and be willing to adhere to the medication regimen.
Patients who are deemed appropriate for definitive, adjuvant, or palliative radiation with total planned dose > 30 Gy.
Patients who are deemed appropriate for concurrent systemic therapy with radiation including cisplatin (100 mg/m2 triweekly or 30-40 mg/m2 weekly), carboplatin (AUC 1-2 weekly) +/- paclitaxel (30 mg/m2 weekly) or cetuximab (400 mg/m2 loading followed by 250 mg/m2 weekly.
a. The final 3 patients in the dose expansion group undergoing the PK/PD study must be deemed appropriate for cisplatin.
For females of reproductive potential: use of highly effective contraception including hormonal contraceptives, intrauterine devices (IUD), vasectomy, tubal ligation, and double barrier methods (combination of male condom, female condom, cervical cap, diaphragm, contraceptive sponge).
For males of reproductive potential: use of condoms.
ECOG performance status ≤ 2.
Exclusion Criteria:
Participation in another clinical study with an investigational product during the last 30 days.
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study, a clinical study not involving pharmaceutical or radiation techniques, or during the follow-up period of an interventional study.
Women who are pregnant or lactating. Patients of reproductive potential must have a negative serum or urine pregnancy test within 72 hours of start of study drug.
Patients who are currently taking gabapentin, pregabalin, amitriptyline, nortriptyline, or duloxetine.
Known allergy or hyposensitivity to alpha lipoic acid.
Judgement by the investigator that the patient is unsuitable to participate in the study and the patient in unlikely to comply with study procedures, restrictions, and requirements.
Facility Information:
Facility Name
Abigail E Berry
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Alpha Lipoic Acid to Decrease Pain and Side Effects in Concurrent Treatment of HNSCC
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