- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02860936
Lenvatinib in Recurrent and/or Metastatic Adenoid Cystic Carcinomas of the Salivary Glands: ACC-LEN14 (ACC-LEN14)
Phase II Study on Lenvatinib in Recurrent and/or Metastatic Adenoid Cystic Carcinomas of the Salivary Glands of the Upper Aerodigestive Tract
Study Overview
Status
Intervention / Treatment
Detailed Description
Carcinomas of the salivary glands (SGCs) are rare, (less than 1% of all cancers of the head and neck and include more than 20 malignant histotypes. They can occur both in major and minor salivary glands, are locally aggressive, demonstrating invasiveness that leads to involvement of the facial nerve, skin, bone and surrounding soft tissue. The standard treatment is surgical excision, followed by radiotherapy in selected cases such as high-grade histotypes, advanced disease and neck nodes diffusion. Loco-regional recurrence occurs in 16% to 85%, it can be managed in very selected cases with further surgery and/or radiotherapy, although the prognosis of these patients remains poor. Adenoid cystic cancer (ACC) is the most common SGC histotype observed in metastatic subjects (60%) and distant metastases are the principal cause of failure, being diagnosed in 25-55% of the patients. First-line treatment is palliative chemotherapy that is typically not associated with any benefit neither in response rate nor in outcome. In preclinical models, VEGF seems to contribute to tumor aggressiveness as well as to distant metastasization, in particular in ACC. Moreover, about 80% of ACC are characterized by MYB-NFIB fusion gene. Deregulation of MYB involves several genes including those associated with apoptosis, cell cycle control and angiogenesis. Clinical evidences support the use of antiangiogenic compounds in ACC. Sorafenib a multi-tyrosine kinase inhibitor (TKI) (VEGFR1-3; PDGFR, RET, cKIT FLT3) and axitinib a potent TKI anti VEGFR1-3 have been tested in advanced ACC, obtaining a 1% of response rate, suggesting some activity agents of this class of drug.
Recently two whole genome sequencing of ACC tumor/normal pairs have found mutations in genes involved in the FGF/IGF/PI3K pathway (up to 30% of the cases) corroborating the hypothesis that this subset might benefit from agents targeting this pathway. Dovitinib, a small molecule that inhibits FGFR, is currently under investigation. Preliminary results indicate that the drug produces objective partial responses and prolonged tumor stabilization in patients with progressive ACCs. Lenvatinib has a stronger antiangiogenic effect compared to sorafenib and axitinib and has also a higher potency with regard to inhibition of FGFR-1, offering a potential opportunity to block one of the well known mechanisms of resistance to VEGF/VEGFR inhibitors. Lenvatinib also has a direct oncogenic effect of controlling tumor cell proliferation by inhibiting RET, c-KIT, and PDGFR beta, as well as an effect on the tumor microenvironment by blocking FGFR and PDGFR beta.
Lenvatinib has been investigated in thyroid cancer and hepatocellular carcinoma (phase III trials) and in other malignancies, showing high rates of activity.
Based on preclinical and clinical data, the investigators believe that targeting angiogenesis, FGFR pathway and tumor microenvironment might represent a rational basis to test lenvatinib in patients with relapsed and/or metastatic ACC.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Milan, Italy, 20133
- Fondazione IRCCS Istituto Nazionale dei Tumori
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically proven relapsed and/or metastatic adenoid cystic carcinoma for which potentially curative options such as surgery or radiotherapy are not indicated.
- Archival tissue samples or unstained 20 slides from primary tumor or metastasis for translational biological research.
- Subjects with at least one uni-dimensional measurable lesion by CT-scan or MRI according to RECIST criteria 1.1 (target lesion). A previously treated lesion by radiotherapy or loco-regional therapies such as radiofrequency (RF) can be chosen as target lesion only if progression in the respective lesion has been demonstrated during or following radiotherapy.
- Clinical or radiological progression of disease within 6 months at study entry. Progression of disease by RECIST is not required.
- Age ≥ 18 years
- ECOG Performance Status < 2
- Life expectancy of > 3 months
- Adequately controlled blood pressure with or without antihypertensive medications, defined as BP < 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to Cycle 1 Day 1
Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
- Hemoglobin >9.0 g/dl
- Neutrophil count (ANC) >1,000/mm3
- Platelet count 75,000/μl
- Total bilirubin <1.5 times the upper limit of normal
- ALT and AST <2.5 x upper limit of normal (<5 x upper limit of normal for patients with liver metastases)
- Serum creatinine <1.5 x upper limit of normal
- Alkaline phosphatase <4 x ULN
- PT-INR/PTT <1.5 x upper limit of normal (Patients who are being therapeutically anticoagulated with an agent such as heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists)
- Previous systemic therapy for metastatic disease is allowed for a maximum of 1 previous line of chemotherapy and/or 1 previous line of TKI
- Signed written informed consent
Exclusion Criteria:
- Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry
- Subjects having > 1+ proteinuria on urine dipstick testing will undergo 24h urine collection for quantitative assessment of proteinuria. Subjects with urine protein ≥ 1 g/24h will be ineligible
- History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
- Gastrointestinal abnormalities (i.e. inability to take oral medication; malabsorption syndrome)
- Requirement for anticoagulant therapy with oral vitamin K antagonists (LMWH therapy is accepted)
- Prolongation of QTc interval to > 480 msec
- Known allergic reaction to any of the components of the treatment
- Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- Legal incapacity or limited legal capacity
- Active clinically serious infections (> grade 2 NCI-CTC version 4.0)
- Medical or psychological condition which, in the opinion of the investigator, would not enable the patient to complete the study or knowingly sign the Informed Consent
- Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and two weeks after the completion of trial
- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.
- Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
- History of organ allograft.
- Patients with evidence or history of bleeding diathesis
- Patients undergoing renal dialysis
- Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry.
- Previous therapy with lenvatinib (E7080)
- Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed)
- Major surgery within 2 weeks of start of study
- Use of biologic response modifiers, such as G-CSF, within 3 week of study entry [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator, however they may not be substituted for a required dose reduction; patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study]
- Investigational drug therapy outside of this trial during or within 4 weeks of study entry
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Lenvatinib
24 mg of lenvatinib will be administered daily to patients until progression of disease or intolerable toxicity or other criteria for discontinuation is met.
|
Lenvatinib will be self orally administered at 24 mg daily, on a continuous basis in 4 week cycles until tumour progression, unacceptable toxicity or other criteria for discontinuation is met.
Study drug should be taken at approximately the same time each morning.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate (CR+PR)
Time Frame: 2 years and 5 months
|
Objective response rate (CR+PR) will be evaluated according to RECIST response evaluation criteria 1.1 at any subsequent re-evaluation
|
2 years and 5 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression free survival
Time Frame: 2 years and 5 months
|
PFS according to RECIST criteria 1.1
|
2 years and 5 months
|
Overall survival
Time Frame: 2 years and 5 months
|
After study drug treatment ends, patients will be contacted each 6 months to determine survival
|
2 years and 5 months
|
Safety and toxicity profile of lenvatinib (according to CTCAE v 4.0)
Time Frame: 2 years and 5 months
|
Incidence of adverse events (AEs), will be graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0, laboratory values, physical examinations, vital signs.
|
2 years and 5 months
|
Duration of response
Time Frame: 2 years and 5 months
|
The duration of response will be evaluated to assess the duration of activity of lenvatinib (CR+PR+SD)
|
2 years and 5 months
|
Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Head and Neck Neoplasms
- Stomatognathic Diseases
- Mouth Diseases
- Salivary Gland Diseases
- Mouth Neoplasms
- Carcinoma
- Carcinoma, Adenoid Cystic
- Salivary Gland Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Lenvatinib
Other Study ID Numbers
- INT 38/15
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Adenoid Cystic Carcinomas of the Salivary Glands
-
Ontario Clinical Oncology Group (OCOG)Novartis PharmaceuticalsCompletedRecurrent Adenoid Cystic Carcinoma of the Salivary Glands | Metastatic Adenoid Cystic Carcinoma of the Salivary Glands | Salivary Gland Cancers | ACCCanada
-
National Cancer Institute (NCI)Southwest Oncology GroupCompletedRecurrent Salivary Gland Cancer | Recurrent Adenoid Cystic Carcinoma of the Oral Cavity | Stage III Adenoid Cystic Carcinoma of the Oral Cavity | Stage III Salivary Gland Cancer | Stage IV Adenoid Cystic Carcinoma of the Oral Cavity | Stage IV Salivary Gland Cancer | Salivary Gland Adenoid Cystic...United States
-
Dana-Farber Cancer InstituteAdenoid Cystic Carcinoma Research FoundationNot yet recruitingAdenoid Cystic Carcinoma | Adenoid Cystic Carcinoma of the Salivary GlandUnited States
-
Nantes University HospitalCompletedNon Tumor Salivary Gland Diseases of the Parotid Glands | Non Tumor Salivary Gland Diseases of the Submandibular Glands
-
Fudan UniversityCompletedCisplatin | Adenoid Cystic CarcinomasChina
-
National Cancer Institute (NCI)CompletedRecurrent Salivary Gland Cancer | Recurrent Adenoid Cystic Carcinoma of the Oral Cavity | High-grade Salivary Gland Carcinoma | High-grade Salivary Gland Mucoepidermoid Carcinoma | Low-grade Salivary Gland Carcinoma | Low-grade Salivary Gland Mucoepidermoid Carcinoma | Salivary Gland Acinic Cell... and other conditionsCanada
-
National Cancer Institute (NCI)CompletedRecurrent Salivary Gland Carcinoma | Stage IVA Major Salivary Gland Cancer AJCC v7 | Stage IVB Major Salivary Gland Cancer AJCC v7 | Stage IVC Major Salivary Gland Cancer AJCC v7 | Tongue Carcinoma | Salivary Gland Adenoid Cystic Carcinoma | Recurrent Oral Cavity Adenoid Cystic Carcinoma | Stage... and other conditionsUnited States, Canada
-
National Cancer Institute (NCI)CompletedRecurrent Salivary Gland Carcinoma | Stage IVA Major Salivary Gland Cancer AJCC v7 | Stage IVB Major Salivary Gland Cancer AJCC v7 | Stage IVC Major Salivary Gland Cancer AJCC v7 | Salivary Gland Adenoid Cystic Carcinoma | Recurrent Oral Cavity Adenoid Cystic Carcinoma | Stage IVA Oral Cavity... and other conditionsUnited States
-
Shanghai Ninth People's Hospital Affiliated to...RecruitingAdenoid Cystic Carcinoma of the Head and NeckChina
-
Groupe Oncologie Radiotherapie Tete et CouRecruitingAdenoid Cystic Carcinoma of the Head and NeckFrance
Clinical Trials on Lenvatinib
-
Memorial Sloan Kettering Cancer CenterCompletedHead and Neck Cancer | Head and Neck Squamous Cell Carcinoma | Head and Neck Carcinoma | Cutaneous Squamous Cell CarcinomaUnited States
-
Fudan UniversityActive, not recruitingHepatocellular CarcinomaChina
-
Regina Elena Cancer InstituteUniversity of Pisa; University of Roma La Sapienza; University of Turin, Italy; Istituto Oncologico Veneto IRCCS and other collaboratorsRecruitingDifferentiated Thyroid Cancer | GenderItaly
-
Shanghai Junshi Bioscience Co., Ltd.Active, not recruitingAdvanced Hepatocellular Carcinoma (HCC)Italy, Poland, Singapore, United States, China, Ukraine
-
Shandong New Time Pharmaceutical Co., LTDRecruitingHepatocellular CarcinomaChina
-
Cancer Institute and Hospital, Chinese Academy...Active, not recruitingHepatocellular Carcinoma | Radiotherapy | LenvatinibChina
-
CStone PharmaceuticalsActive, not recruitingHepatocellular CarcinomaSpain, China, United States, Poland, Italy, Taiwan
-
Eisai Inc.Merck Sharp & Dohme LLCCompletedSolid TumorsUnited States, China, Belgium, Australia, Italy, Korea, Republic of, Germany, Netherlands, Poland, Romania, Thailand
-
Eisai Inc.CompletedThyroid CancerUnited States, Australia, France, Poland, United Kingdom, Italy
-
Shanghai Zhongshan HospitalActive, not recruitingCholangiocarcinoma, IntrahepaticChina