Phase II Trial of HM781-36B in Patients With Metastatic/Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC) After Failure of or Unfit for Platinum-containing Therapy
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|ClinicalTrials.gov Identifier: NCT02216916|
Recruitment Status : Unknown
Verified March 2019 by Yonsei University.
Recruitment status was: Recruiting
First Posted : August 15, 2014
Last Update Posted : March 18, 2019
Head and neck cancer is the sixth most common cancer and more than 650,000 new cases are diagnosed each year worldwide. About 60% of the HNSCC patients present with unresectable locally advanced disease at diagnosis and treated with multimodality approach. Despite such approach, majority (70%) of patients develop local or/and regional recurrences. Additional 10% of patients present with distant metastasis at diagnosis. Most patients with recurrent or metastatic disease are treated with single agent chemotherapy, combination chemotherapy or targeted therapies.
Despite its public health magnitude, HNSCC in Asian countries has received a limited attention for the drug development and cancer-related research. In fact, HNSCC ranked 7th among men and 10th among women by incidence in China, the largest producer and consumer of tobacco and alcohol. Recently, Chen et al. documented a 1:1:2 subset distribution for cancers of oral cavity, pharynx, and larynx in China, similar to the distribution reported in Korea but quite different from the general distribution of 5:2:3 in whites. Ethnic disparities in HNSCC also include its prognosis and this is partly explained by HPV-active disease ratio and genetic factors. Therefore, there is a strong need for an additional research in patients with HNSCC in Asia.
Epidermal growth factor receptor (EGFR) is often over-expressed, and have been related to poor prognosis in patients with HNSCC. The association between EGFR-activated signaling pathways and tumor cell survival are well documented in many studies. EGFR targeting strategies showed clinical anti-tumor efficacy in patients with HNSCC, especially with monoclonal antibody, cetuximab. In the Extreme study, it was shown that the addition of cetuximab to platinum-5-FU significantly prolonged the median overall survival from 7.4 months to 10.1 months compared to platinum-5FU alone in the first-line setting.
HM781-36B is a irreversible pan-HER inhibitor. In preclinical studies, HM781-36B has much lower IC50 values than gefitinib in cell lines engineered to express EGFRvIII mutations and produces tumor growth inhibition in gefitinib-resistant xenografts. A phase I trial of HM781-36B in patients with advanced solid tumors showed clinically significant anti-tumor activity and a phase II trials of HM781-36B in patients with non-small cell lung cancer and advanced gastric cancer are currently ongoing.
We suggest a phase II trial of HM781-36B 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 HM781-36B and to identify biomarker to predict the tumor response to HM781-36B.
|Condition or disease||Intervention/treatment||Phase|
|HNSCC||Drug: HM781-36B||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||49 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Study Start Date :||August 2014|
|Estimated Primary Completion Date :||July 2019|
|Estimated Study Completion Date :||July 2019|
Other Name: 45 mg p.o. daily and continuously (28-day treatment as one treatment cycle)
- Response rate [ Time Frame: 28th day of 1st chemotherapy cycle ]Objective Tumor Response will be performed according to the Response Evaluation in Solid Tumor Criteria 1.1 (RECIST 1.1)
- Best Overall Response [ Time Frame: 1years ]
- Duration of response [ Time Frame: 1years ]
- Progression-Free Survival [ Time Frame: 1years ]
- Overall Survival [ Time Frame: 1years ]
- Toxicity profile [ Time Frame: 1years ]Overall safety profile and toleration of HM781-36B will be characterized by type, frequency, severity (as graded by the NCI CTCAE v4.02), timing and relationship of study therapy of adverse events and laboratory abnormalities. Quantitative variables will be summarized in descriptive terms.
- Quality of Life (QoL) [ Time Frame: 1years ]Questionnaire
- Identification of predictive markers of treatment [ Time Frame: 1years ]
- To explore KRAS and HER family mutation status in tissue at the end of treatment;
- To explore the pre- and post-treatment levels of shed proteins/receptors related to HER signaling (possibly to include EGFR and HER-2 receptor extracellular domain (ECD) and E-cadherin);
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02216916
|Korea, Republic of|
|Seoul, Korea, Republic of|
|Contact: Cho Byung Chul 82-10-5212-8867 ext 84320 firstname.lastname@example.org|