HNSCCPhase 2NCT02216916
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
A Phase 2 study testing HM781-36B in people with HNSCC, run by Yonsei University at 1 site in South Korea.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- HNSCC
- What is being tested?
- HM781-36B
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteSouth Korea
- Study dates
- Aug 2014to Jul 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed squamous cell carcinoma of head and neck
- Age ≥ 20 years
- ECOG PS 0-1
- Documented progressive disease after platinum-based (either cisplatin or carboplatin) concurrent chemoradiation including induction chemotherapy for curative aim or
- Documented progressive disease after platinum-based (either cisplatin or carboplatin) chemotherapy for palliative aim or
- Ineligible to platinum-based (either cisplatin or carboplatin) chemotherapy or chemoradiation due to decline in renal function and patient's intolerance
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- At least one bidimensionally measurable disease as defined by RECIST ver 1.1
- Adequate organ function for treatment
- Absolute neutrophil count (ANC) ≥ 1000cells/mm3
- Platelets ≥ 100000 cells/mm3
- Estimated creatinine clearance ≥ 50mL/min, or serum creatinine < 1.5 x institution upper limit of normal
- Bilirubin ≤ 1.5 x upper limit of normal(ULN)
- AST(SGOT) ≤ 2.5 x ULN (5.0xULN if hepatic metastases)
- ALT(SGPT) ≤ 2.5 x ULN (5.0xULN if hepatic metastases)
- The patient has provided signed informed consent and is amenable to compliance with protocol schedules and testing
Who cannot join
- Nasopharyngeal carcinoma
- Patients who are subjected to local treatment (surgery or radiation)
- Previous treatment with small molecule EGFR tyrosine kinase inhibitors (Cetuximab is permitted)
- Three or more previous systemic cytotoxic chemotherapy
- Any major operation or irradiation within 4 weeks of baseline disease assessment
- Patients who have received prior systemic chemotherapy, immunotherapy or study drug within 4 weeks
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- Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug
- Patients with uncontrolled CNS metastatic involvement. However, patients with metastatic CNS tumors may participate in this study if the patient is clinically stable not receiving steroid therapy more than 1 week from prior therapy completion (including radiation and/or surgery) to stating the study drug.
- Patients with known interstitial lung disease (ILD) or presented ILD on screening chest X-ray
- Congenital long QT syndrome or screening corrected QT interval (QTc) > 470msec
- Patients with uncontrolled or significant cardiovascular disease (AMI within 12 months, Unstable angina within 6 months, NYHA Class III, IV Congestive heart failure or left ventricular ejection fraction below local institutional lower limit of normal or below 45%, Congenital long QT syndrome, Any significant ventricular arrhythmia, Any uncontrolled second or third degree heart block, Uncontrolled hypertension)
- Previous or concurrent malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to study entry.
- Pregnant or breast-feeding women
- Other severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial.
Trial locations and contacts
1 site in 1 country.
South Korea1 site, 1 recruiting
- Recruiting
Yonsei University
Seoul
Cho Byung Chul, 82-10-5212-8867 ext. 84320, cbc1971@yuhs.ac
About this study
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.
Read more
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.
- Conditions
- HNSCC
- Being tested
- HM781-36B
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HM781-36BDrug
Also called 45 mg p.o. daily and continuously (28-day treatment as one treatment cycle)
| Study group | Role | What they receive |
|---|---|---|
| HM781-36B | Experimental | Not described Receives: Drug: HM781-36B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate
Objective Tumor Response will be performed according to the Response Evaluation in Solid Tumor Criteria 1.1 (RECIST 1.1)
Measured: 28th day of 1st chemotherapy cycle
Secondary outcomes (7)
Best Overall Response
Measured: 1years
Duration of response
Measured: 1years
Progression-Free Survival
Measured: 1years
Overall Survival
Measured: 1years
Toxicity profile
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.
Measured: 1years
Quality of Life (QoL)
Questionnaire
Measured: 1years
Identification of predictive markers of treatment
- 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);
Measured: 1years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2014 (estimated)
- Study startAug 2014
- Primary completionJul 2019 (estimated)
- Study completionJul 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HNSCCStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02216916
- Sponsor's protocol ID
- 4-2013-0794
- Status last verified
- Mar 2019
- First submitted
- 13 Aug 2014
- Last updated
- 18 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lee JH, Heo SG, Ahn BC, Hong MH, Cho BC, Lim SM, Kim HR. A phase II study of poziotinib in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Cancer Med. 2021 Oct;10(20):7012-7020. doi: 10.1002/cam4.4231. Epub 2021 Sep 16.
PubMed 34528763
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02216916
- Acronym / sponsor ID
- 4-2013-0794
- Conditions
- HNSCC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 49 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- Jul 2019 (estimated)
- Study completion
- Jul 2019 (estimated)
- First posted
- 15 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HM781-36B | Experimental | Drug: HM781-36B |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically confirmed squamous cell carcinoma of head and neck
- Age ≥ 20 years
- ECOG PS 0-1
- At least one bidimensionally measurable disease as defined by RECIST ver 1.1
- Adequate organ function for treatment
Key exclusion criteria (14 listed)
- Nasopharyngeal carcinoma
- Patients who are subjected to local treatment (surgery or radiation)
- Previous treatment with small molecule EGFR tyrosine kinase inhibitors (Cetuximab is permitted)
- Three or more previous systemic cytotoxic chemotherapy
- Any major operation or irradiation within 4 weeks of baseline disease assessment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HM781-36BAlso: 45 mg p.o. daily and continuously (28-day treatment as one treatment cycle) | Drug | HM781-36B |
Primary outcome
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)
7 secondary outcomes
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
Quality of Life (QoL)
Time frame: 1years
Identification of predictive markers of treatment
Time frame: 1years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2019.
- Derived from this study: PubMed 34528763Lee JH, Heo SG, Ahn BC, Hong MH, Cho BC, Lim SM, Kim HR. A phase II study of poziotinib in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Cancer Med. 2021 Oct;10(20):7012-7020. doi: 10.1002/cam4.4231. Epub 2021 Sep 16.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HM781-36B in people with HNSCC, run by Yonsei University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response rate (time frame: 28th day of 1st chemotherapy cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02216916, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2019.