Chidamide Combined With Cisplatin in Head and Neck Adenoid Cystic Carcinoma (HNACC)

Chidamide Combined With Cisplatin in Recurrent or Metastatic Head and Neck Adenoid Cystic Carcinoma: A Prospective, Open-label, Phase II Study of a Single Center

The investigators conducted this study to evaluate the efficacy of Chidamide combined with cisplatin in recurrent or metastatic head and neck adenoid cystic carcinoma.

Study Overview

• Status: Completed
• Conditions: Cisplatin; Adenoid Cystic Carcinomas
• Intervention / Treatment: Drug: Chidamide combined with cisplatin

Detailed Description

Adenoid cystic carcinomas (ACCs) constitute of 1% of head and neck cancers. This type of tumor grows slowly with a high potential of local recurrence. Approximately 50% of patients develop distant metastases, and 33% patients die within 2 years. The initial therapy of these malignancies consists of surgical resection followed by radiotherapy. Systemic therapy is crucial in the management of recurrent and metastatic disease. However, nowadays, there were no standard chemoimmunotherapy regimes. Previous report showed that overall response rate was only less than 10% using single-agent chemotherapies, and the best results were achieved by cisplatin. Chidamide is a new benzamide class of histone deacetylase inhibitor with marked antitumor activity. And a phase I study has showed that one of three patients with submandibular adenoid cystic carcinoma achieved a partial response treated with Chidamide. The investigators conducted this study to evaluate the efficacy of Chidamide combined with cisplatin in recurrent or metastatic head and neck adenoid cystic carcinoma, in order to find a potential promising way to treat this kind of disease.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Kai Xue

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age range 18-75 years old
2. Histological confirmed recurrent or metastatic head and neck adenoid cystic carcinoma
3. Unable to treat with surgery/radiotherapy, or previously failure to non-cisplatin systematic treatment;
4. Eastern Cooperative Oncology Group performance status 0 to 2;
5. Patients have written informed consent to participate in the study;
6. anticipated to live ≧3 months;
7. Absolute neutrophil count ≥ 1.5×109/L，platelet ≥ 100×109/L，hemoglobin ≥ 90 g/L
8. total bilirubin < 1.5×upper limit of normal(ULN), ALT and AST < 3× ULN
9. serum creatine <1.5×ULN, and creatinine clearance rate (CCR) ≥ 50 ml/min
10. Ultrasonic cardiogram showed left ventricle ejection fraction ≥ 50%, EKG showed no signs of myocardial ischemia, with no previous arrhythmia which need pharmacological intervention.
11. Measurable disease was defined as at least one lesion ≥1.5 cm in length-diameter and ≥0.5 cm in short-diameter by CT.

Exclusion Criteria:

1. Previously treated with HDACi;
2. Treated with cisplatin-contained regimes in the past half of the year, and not achieving PR/CR;
3. History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix;
4. HIV, HCV, or syphilis infection；
5. Pregnant or lactating women;
6. Serious uncontrolled infection;
7. Severe neurol of mental illness, including dementia and epilepsy;
8. Having contraindications to the use of oral medication, such as unable to swallow, nausea and vomiting, chronic diarrhea or suffering from a bowel obstruction;
9. Participated in other clinical trials in 4 weeks;
10. Other coexisting diseases or situations that may cause patients to fail to complete clinical trials;
11. History of QTc interval prolongation (Male >450ms，Female >470ms), ventricular tachycardia, auricular fibrillation, heart block of more than II degrees, myocardial infarction in 1 year, congenital heart disease, with symptomatic coronary heart disease requiring medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chidamide combined with Cisplatin; Chidamide: 30mg,PO,biw one week before cycle 1 treatment Cisplatin 25mg/m2 ivgtt D1-3 Chidamide :20mg PO Biw, 2 week on , 1 week off	Drug: Chidamide combined with cisplatin; Chidamide combined with cisplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	Defined as numbers of patients achieved complete response and patial response of treatment	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	Defined as numbers of patients achieved complete response, patial response, and stable disease of treatment	6 weeks
Progression-free survival (PFS)	Defined as the time from randomization until objective tumor progression or death	6 weeks
Scoring of quality of life: EORTC-QLQ-30	Quality of life was evaluated using EORTC-QLQ-30. All subscales are summed to compute a total score, and total scores are recorded. Lower scores represent a better outcome.	6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum ctDNA biomarker	relationship between biomarker and treatment outcome	throughout the treatment period，up to 6 months

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Kai Xue, MD, Department of medical oncology,Fudan University, Shanghai Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2018
• Primary Completion (Actual): June 24, 2020
• Study Completion (Actual): June 2, 2021

Study Registration Dates

• First Submitted: August 4, 2018
• First Submitted That Met QC Criteria: August 16, 2018
• First Posted (Actual): August 21, 2018

Study Record Updates

• Last Update Posted (Actual): August 19, 2021
• Last Update Submitted That Met QC Criteria: August 18, 2021
• Last Verified: August 1, 2021

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; Cisplatin
• Other Study ID Numbers: CC-HN-1

Drug and device information, study documents

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