All-trans Retinoic Acid (ATRA) in the Treatment of Recurrent/Metastatic Adenoid Cystic Carcinoma of the Head and Neck (Aplus)

A Prospective, Open-label, Randomized Controlled Clinical Study to Evaluate the Efficacy and Safety of All-trans Retinoic Acid (ATRA) in the Treatment of Patients With Recurrent/Metastatic Adenoid Cystic Carcinoma of the Head and Neck

This is a prospective, open-label, randomized controlled clinical intervention study to evaluate the efficacy and safety of all-trans retinoic acid (ATRA) in treating patients with recurrent metastatic adenoid cystic carcinoma of the head and neck.

Study Overview

• Status: Recruiting
• Conditions: Adenoid Cystic Carcinoma of the Head and Neck
• Intervention / Treatment: Drug: All-trans Retinoic Acid; Drug: VEGFR inhibitor; Drug: Chemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Guopei Zhu, M.D; Phone Number: 5665 021-23271699; Email: antica@gmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200011
      • Recruiting
      • Shanghai Ninth People's Hospital
      • Contact: Lulu Ye, Master; Phone Number: 5665 021-23271699; Email: yee166@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years, male or female; 2. ECOG PS (performance status) score: 0-1; 3. Pathologically or histologically confirmed advanced, recurrent/metastatic ACC, with measurable disease (≥10 mm by spiral CT scan, meeting RECIST 1.1 criteria); 4. Patients with therapeutic indications; 5. Main organ functions normal, i.e., meeting the criteria below:

1. Criteria for routine blood test: (no blood transfusion within 14 days)

   1. HB ≥ 90 g/L;
   2. WBC ≥ 3.5 × 109/L and < 10 × 109/L;
   3. ANC ≥ 1.5 × 109/L;
   4. PLT ≥ 80 × 109/L

2. Criteria for biochemical tests:

   1. BIL < 1.25 × upper limit of normal (ULN)
   2. ALT and AST < 2.5 × ULN; in the presence of metastases to liver, ALT and AST < 5 × ULN;
   3. Serum Cr ≤ 1 × ULN, endogenous creatinine clearance > 50 mL/min (Cockcroft-Gault equation); 5. Subjects who volunteer to participate in this study, sign the informed consent, have good compliance and cooperate in follow-up; 6. Patients who, in the doctor's opinion, can benefit from the treatment.

Exclusion Criteria:

1. Previous or existing concomitant malignancies except cured skin basal cell carcinoma or cervical carcinoma in situ;
2. Coagulation abnormal (INR>1.5, APTT>1.5×ULN), history of gastrointestinal hemorrhage in the past 6 months or bleeding tendency [e.g., presence of active ulcer focus in the stomach, stool occult blood (++), melena and/or hematemesis, hemoptysis in the past 3 months];
3. Confirmed hypersensitivity to ATRA;
4. Grade I and above coronary artery diseases, arrhythmias [including QTc prolongation (males: > 450 ms, females: > 470 ms)] and cardiac dysfunction;
5. Presence of multiple factors affecting oral administration (e.g. dysphagia, nausea, vomiting, chronic diarrhea and intestinal obstruction, etc.);
6. Pregnant or lactating women;
7. History of psychotropic abuse with abstinence failure, or existing mental disorder;
8. Participation in other drug clinical trials within 4 weeks;
9. Other concomitant diseases which seriously jeopardize the patient's safety or prevent the patient from completing the study, as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; ATRA 20 mg, three times a day (tid), for 28 consecutive days, 28 days per cycle (q4w), 6 planned cycles; combined with the treatment regimen chosen by the investigator since Day 6 of cycle 1.	Drug: All-trans Retinoic Acid; ATRA 20 mg, three times a day, for 28 consecutive days, 28 days per cycle (q4w), 6 planned cycles; Other Names: Ailike
Active Comparator: Control group; The investigator chooses the treatment regimen based on the following regimens (including but not limited to: 1. VEGFR inhibitor; 2. chemotherapy).	Drug: VEGFR inhibitor; VEGFR inhibitor; Drug: Chemotherapy; chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (CR+PR)	Objective Response Rate as defined by RECIST 1.1 after induction therapy followed by definitive chemoradiation. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With at Least One Grade 3-4 Toxicity	Toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.	6 months
Progression-Free Survival	Time to death or progression defined by imaging of target lesions via CT or MRI scan every 3 months.	6 months

Collaborators and Investigators

• Sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: June 12, 2020
• First Submitted That Met QC Criteria: June 15, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): February 2, 2021
• Last Update Submitted That Met QC Criteria: January 31, 2021
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Adenoid Cystic; Antineoplastic Agents; Dermatologic Agents; Keratolytic Agents; Tretinoin
• Other Study ID Numbers: 2020HNRT02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No