Study of CX1106 in Patients With Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)

A Clinical Trial to Evaluate the Efficacy and Safety of CX1106 in Patients With Metastatic/Recurrent Head and Neck Squamous Cell Carcinoma After Failure of or Unfit for Platinum-containing Therapy

CX1106 is a novel inhibitor of thymidylate synthase (TS) developed as a potential antitumor agent by virtue of the rate limiting role of TS in the biosynthesis of thymidine. CX1106 differs from other TS inhibitors such as pemetrexed, raltitrexed, CB3717, and fluorouracil in that it does not require active transport for uptake into cells. CX1106 also lacks a glutamate moiety and thus does not require polyglutamation for antitumor activity. More than 1000 patients with various malignancies have been treated with CX1106 to date in previous various clinical trials.

The investigators suggest a study of CX1106 in patients with recurrent or metastatic HNSCC who are resistant or ineligible/intolerant to platinum-based chemotherapy. The aim of current trial is to evaluate the antitumor efficacy and safety profile of CX1106.

Study Overview

• Status: Withdrawn
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: CX1106

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically or cytologically confirmed HNSCC (excluding nasopharyngeal carcinoma);
• At least one measurable lesion (spiral CT scan long diameter ≥ 10 mm or enlarged lymph node short diameter ≥ 15 mm by RECIST 1.1);
• Documented disease progression after prior platinum-based systematic therapy; or prior platinum-based adjuvant/neoadjuvant therapy with documented disease progression within 24 weeks after treatment completion;
• Expected overall survival≥ 3 months;
• ECOG PS≤1;

Exclusion Criteria:

•Hematologic, renal, and hepatic function as defined below:

Absolute neutrophil count (ANC) <1.5×109 /L or platelet <100×109 /L or hemoglobin <9 g/dL; Total bilirubin >1.5×the upper limit of normal range(ULN); Aspartate aminotransferase (AST) and/or Alanine transaminase (ALT) and/or Alkaline phosphatase (ALP) >1.5×ULN without liver metastases ; AST and/or ALT and/or ALP levels >5×ULN with liver metastases. Primary hepatocellular carcinoma: Child-Pugh liver is grade C; Serum creatinine>1.5 ×ULN or creatinine clearance (CL) < 60 mL/min; International normalized ratio (INR) or activated partial thromboplastin time (aPPT) >1.5×ULN;

• Patients who has accepted systemic anti-tumor therapy, including chemotherapy, radiotherapy, hormonal therapy , biologics therapy or immunotherapy within 4 weeks;
• Any unresolved Grade ≥2 toxicity by NCI CTCAE 5.0 from previous anticancer therapy excluding skin pigmentation and alopecia;
• Untreated brain metastases or symptoms of brain metastases cannot be controlled more than 4 weeks;
• Other kinds of malignancies [excluding stage IB or lower grade cervical cancer，noninvasive basal cell or squamous cell cancer, breast cancer with complete remission (CR) > 10 years ,melanoma with CR >10 years or other malignant tumors with CR > 5 years];
• Any of the following gastrointestinal disease:

Need intravenous nutrition; Received treatment for active peptic ulcer disease in the past 6 months; Active gastrointestinal bleeding unrelated to cancer in the past 3 months; Persistent 3 or 4 grade chronic diarrhea although with treatment;

• Presence of hemorrhage (hemoptysis) , thrombosis，or currently receiving treatment with warfarin, aspirin, low molecular weight heparin (LMWH), or any other anti-platelet drugs(low dose of abovementioned drugs for prophylaxis are allowed);
• Active infections, mental and neurological diseases;
• Prior to enrollment within 12 months , patients who had cardiovascular and cerebrovascular disease, deep vein thrombosis or pulmonary embolism within 6 months; or uncontrolled hypertension,systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥ 90 mmHg;
• Prior to enrollment within 30 days , patients who had Major surgical procedure, open biopsy, or significant traumatic injury;
• Hepatitis B surface antigen (HBsAg) positive and HBV-DNA≥ 2000 IU / mL;hepatitis C virus (HCV) antibody positive; and cirrhosis;
• Known history of human immunodeficiency virus (HIV) infection;
• Pregnant or lactating women or those who do not take contraceptives, including men;
• Prior to enrollment within 30 days , patients who have participated in other clinical trials of anti-tumor medicine;
• Diseases which would severely endanger the security of patients or influence the completion of this research.

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: CX1106; CX1106 740 mg/m2 as a 24-hour continuous infusion for 5 days every 3 weeks (3 weeks/cycle, 4-6 cycles)	Drug: CX1106; administration of CX1106 at 740 mg/m2 as a 24-hour continuous infusion for 5 days (120 h, d1-5), 21 days per cycle, no more than 6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Defined as the percentage of subjects with confirmed complete response (CR) or partial response (PR) according to the Response Evaluation in Solid Tumor Criteria 1.1 (RECIST 1.1)	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	Defined as the proportion of patients with confirmed complete response, partial response, and stable disease (CR + PR + SD) according to the Response Evaluation in Solid Tumor Criteria 1.1 (RECIST 1.1)	up to 24 months
Progression-free survival (PFS)	Defined as the duration time from the first CX1106 administration to confirmed disease progression (PD) or death of any reason, whichever occurred first	up to 24 months
Safety profile as assessed by the incidence, duration, and severity of adverse events	Incidence, duration, and severity of AEs measured by laboratory assessments and physical findings according to NCI CTCAE 5.0	up to 24 months

Collaborators and Investigators

• Sponsor: Beijing Konruns Pharmaceutical Co., Ltd.
• Collaborators: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
• Investigators: Principal Investigator: YuanKai Shi, Doctor, Cancer Hospital Chinese Academy of Medical Science

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2019
• Primary Completion (Actual): March 31, 2020
• Study Completion (Actual): March 31, 2020

Study Registration Dates

• First Submitted: September 10, 2019
• First Submitted That Met QC Criteria: September 14, 2019
• First Posted (Actual): September 17, 2019

Study Record Updates

• Last Update Posted (Actual): September 3, 2020
• Last Update Submitted That Met QC Criteria: September 1, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: KC-DIAO-004

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