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

NCT04093115 | Withdrawn Phase 2

• 1 other identifier: KC-DIAO-004
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Disease control rate (DCR)

  up to 24 months

• Progression-free survival (PFS)

  up to 24 months

• Safety profile as assessed by the incidence, duration, and severity of adverse events

  up to 24 months

Study Arms (1)

CX1106

EXPERIMENTAL

CX1106 740 mg/m2 as a 24-hour continuous infusion for 5 days every 3 weeks (3 weeks/cycle, 4-6 cycles)

Drug: CX1106

Interventions

CX1106 DRUG

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

CX1106

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Beijing Konruns Pharmaceutical Co., Ltd.: lead
• Chinese Academy of Medical Sciences: collaborator

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• YuanKai Shi, Doctor

  Cancer Hospital Chinese Academy of Medical Science

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2019
• First Posted: September 17, 2019
• Study Start: December 9, 2019
• Primary Completion: March 31, 2020
• Study Completion: March 31, 2020
• Last Updated: September 3, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share