Clinical trial NCT04042935: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: HNSCC
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Cancer League of Colorado
First posted: 2019-08-02
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention 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
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: Inclusion Criteria:

1. Provision to sign and date the consent form.
2. Stated willingness to comply with all study procedures and be available for the duration of the study.
3. Be a male or female aged 18-100.
4. Histologically or cytologically confirmed stage II-IVB HNSCC of the oral cavity, hypopharynx, oropharynx, larynx, or nasopharynx.
5. Ability to take medication orally or per feeding tube and be willing to adhere to the medication regimen.
6. Patients who are deemed appropriate for definitive, adjuvant, or palliative radiation with total planned dose \> 30 Gy.
7. 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.
8. 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).
9. For males of reproductive potential: use of condoms.
10. ECOG performance status ≤ 2.

Exclusion Criteria:

1. Participation in another clinical study with an investigational product during the last 30 days.
2. 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.
3. 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.
4. Patients who are currently taking gabapentin, pregabalin, amitriptyline, nortriptyline, or duloxetine.
5. Known allergy or hyposensitivity to alpha lipoic acid.
6. 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.

Primary outcomes:
measure: MTD and RP2D of ALA during chemoradiotherapy for HNSCC patients
timeFrame: 18 months
Secondary outcomes:
measure: Safety of ALA by following adverse events (AEs)
timeFrame: up to 18 months
measure: Maximum plasma concentration of ALA at the MTD with chemoradiotherapy
timeFrame: At start of ALA, Day 1, and Day 15, for 3 dose expansion PK patients
measure: Change in Oral Mucositis Assessment Scale (OMAS) from baseline
timeFrame: From start of treatment to post-treatment surveillance scans, up to 6 months
measure: Change in Visual Assessment Score (VAS) for pain from baseline
timeFrame: From start of treatment to post-treatment surveillance scans, up to 6 months
measure: Change in quality of life measures using the Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN) during chemoradiation
timeFrame: From start of treatment to post-treatment surveillance scans, up to 6 months
measure: Total concurrent opioid use using patient reported diaries
timeFrame: From start of treatment to post-treatment surveillance scans, up to 6 months
measure: Progression free survival (PFS)
timeFrame: Screening, 3 and 6 month follow up visits
measure: Overall survival (OS)
timeFrame: From start of treatment up to 18 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Jessica McDermott
role: PRINCIPAL_INVESTIGATOR
References: