Lenvatinib in Recurrent and/or Metastatic Adenoid Cystic Carcinomas of the Salivary Glands: ACC-LEN14

NCT02860936 | Completed Phase 2

• 1 other identifier: INT 38/15
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

ACC is rare and represent approximately 25% of salivary gland carcinomas. The standard treatment is surgical excision followed by radiotherapy in selected cases. The disease is characterized by a progressive course with local and distant recurrences. First-line treatment is palliative chemotherapy that had modest results. Expression of the epidermal growth factor receptor in ACC of salivary origin has been reported. Several papers report that a high percentage of ACCs carries a chromosome translocation that results in the overexpression of the oncogene MYB, which is involved in cell proliferation, apoptosis, differentiation and in upregulation of several growth and angiogenetic factors contributing to the autocrine activation of the FGFR and VEGFR-mediated angiogenesis. Recently two whole genome sequencing of several ACC tumor/normal pairs have found mutations in genes involved in the FGF/IGF/PI3K pathway corroborating the hypothesis that this subset might benefit from inhibitors of this pathway. Based on these premises several antiangiogenic drugs and FGFR inhibitors are currently under investigation and a response rate of 11% was observed in ACC. Lenvatinib is an oral multiple RTK inhibitor targeting VEGFR-1-3, FGFR-1-4, RET, c-KIT, and PDGFR. On February 13, 2015 the drug has been approved by FDA for the treatment of patients with locally recurrent or metastatic, radioactive iodine-refractory differentiated thyroid cancer. 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.

Conditions

Adenoid Cystic Carcinomas of the Salivary Glands

Outcome Measures

Primary Outcomes (1)

• Objective response rate (CR+PR)

  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 Outcomes (4)

• Progression free survival

  2 years and 5 months

• Overall survival

  2 years and 5 months

• Safety and toxicity profile of lenvatinib (according to CTCAE v 4.0)

  2 years and 5 months

• Duration of response

  2 years and 5 months

Study Arms (1)

Lenvatinib

EXPERIMENTAL

24 mg of lenvatinib will be administered daily to patients until progression of disease or intolerable toxicity or other criteria for discontinuation is met.

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

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.

Also known as: Lenvima

Lenvatinib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Related Publications (1)

• Locati LD, Galbiati D, Calareso G, Alfieri S, Singer S, Cavalieri S, Bergamini C, Bossi P, Orlandi E, Resteghini C, Platini F, Granata R, Quattrone P, Mancinelli M, Mariani L, Lo Vullo S, Licitra LF. Patients with adenoid cystic carcinomas of the salivary glands treated with lenvatinib: Activity and quality of life. Cancer. 2020 Jan 1;126(9):1888-1894. doi: 10.1002/cncr.32754. Epub 2020 Feb 7.

  PMID: 32031693 DERIVED

MeSH Terms

Interventions

lenvatinib

Study Officials

• Lisa Licitra

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 2, 2016
• First Posted: August 10, 2016
• Study Start: June 1, 2015
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: September 3, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)