A Phase II Study of Lenvatinib Plus Pembrolizumab in Patients With Progressive, Recurrent/Metastatic Adenoid Cystic Carcinoma and Other Salivary Gland Cancers

Memorial Sloan Kettering Cancer Center8 sites in 1 country64 target enrollmentJune 2, 2020

ConditionsAdenoid Cystic Carcinoma Salivary Gland Cancer

InterventionsLenvatinib Pembrolizumab

DrugsLenvatinib Pembrolizumab

Overview

Phase: Phase 2
Intervention: Lenvatinib
Conditions: Adenoid Cystic Carcinoma
Sponsor: Memorial Sloan Kettering Cancer Center
Enrollment: 64
Locations: 8
Primary Endpoint: best overall response rate
Status: Active, not recruiting
Last Updated: 6 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to see if the study drugs, lenvatinib and pembrolizumab, are effective in treating advanced Adenoid Cystic Carcinoma (ACC) or other salivary gland cancers that have come back and/or spread to other parts of the body. Researchers are also doing this study to test the safety of the study drugs in participants.

Registry

clinicaltrials.gov

Start Date

June 2, 2020

End Date

December 1, 2026

Last Updated

6 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Memorial Sloan Kettering Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•ACC Cohort (Cohort 1) only: Patients must have pathologically or cytologically confirmed adenoid cystic carcinoma. Cancers arising from non-salivary gland primary sites are allowed.
•Non-ACC Cohort (Cohort 2) only: Patients must have pathologically or cytologically confirmed salivary gland cancer of any histology (except for adenoid cystic carcinoma that is enrolled into cohort 1).
•Patients must have recurrent and/or metastatic disease not amenable to other curative intent therapy.
•At least 4 weeks must have elapsed since the end of prior systemic treatment and/or since completion of radiotherapy with resolution of all treatment related toxicity to NCI CTCAE Version 5.0 grade ≤1 (or tolerable grade 2) or back to baseline (except for alopecia, lymphopenia, or hypothyroidism) prior to starting study drug treatment.
•Patients must have RECIST V1.1 measurable disease defined as at least one non-nodal lesion measuring ≥ 20 mm with conventional techniques or as ≥10mm with CT scan, MRI, or calipers by clinical exam in the longest dimension AND/OR a nodal lesion measuring \> 15 mm in the shortest dimension. Tumors in previously irradiated fields may be considered measurable if there is evidence of tumor progression after radiation treatment.
•Cohort 1 and acinic cell carcinoma patients in Cohort 2 only: Patients must have documentation of a new or progressive lesion on radiologic imaging study performed within 6 months prior to study enrollment (progression of disease over any interval is allowed) and/or new/worsening disease related symptoms within 6 months prior to study enrollment. Note: This assessment will be performed by the treating investigator and evidence of progression by RECIST criteria is not required.
•Age ≥ 18 years of age on the day of signing informed consent.
•ECOG performance status 0 or 1 (or Karnofsky ≥ 70%).
•Patients must have tissue from the primary tumor or metastases available for correlative studies. Either a paraffin block or at least 20 unstained slides are acceptable (paraffin block or at 30 unstained slides would be ideal). Patients without available tissue for submission may still be eligible if approved by the Principal Investigator.
•Screening laboratory values must meet the following criteria:

Exclusion Criteria

•Untreated metastatic brain (subjects with treated brain metastases will be eligible, provided that they are radiographically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to the first dose of study treatment).
•Concurrent anti-cancer therapy (chemotherapy, definitive radiation therapy, surgery, immunotherapy, biologic therapy or tumor embolization) other than study treatment. Concurrent therapy with bisphosphonates or denosumab for bone metastases is allowed, provided they are started prior to study entry. Palliative radiation to non-target lesions is also allowed.
•Prior malignancy if diagnosed and treated within 2 years of trial drug initiation (with the exception of non-melanomatous skin cancers). Patients may be included if they have completed therapy for a prior malignancy \>2 years prior to drug initiation and are currently NED. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (breast DCIS, or cervical CIS) that have undergone potentially curative at any time therapy are not excluded from trial participation.
•History of allergy or intolerance to study drug components (or any of their excipients), or severe (\> Grade 3) hypersensitivity reaction to any excipients of pembrolizumab or any monoclonal antibody.
•Prior use of lenvatinib or any PD-1/PD-L1 or anti-PD-L2 targeted therapies or with an agent directed at another stimulatory or co-inhibitory T-cell receptor (CTLA-4, OX-40, CD137).
•Uncontrolled hypertension (systolic pressure \>140mm Hg or diastolic pressure \>90mm Hg), despite optimal medical management.
•Prior systemic anti-cancer therapy including use of another investigational drug or device (i.e., outside study treatment) during, or within 4 weeks of trial entry (time of initiation of experimental drug).
•Clinically significant proteinuria:
•°Subjects having \>1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with proteinuria ≥1gm/24-hour will be ineligible.
•Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.

Arms & Interventions

recurrent/metastatic non-ACC salivary gland cancers (R/M SGC).

All eligible patients will undergo informed consent and screening for trial enrollment. Enrolled patients will receive a starting lenvatinib dose of 20mg daily taken orally and pembrolizumab 200mg intravenously every 3 weeks (1 cycle=3 weeks)

Intervention: Lenvatinib

recurrent/metastatic adenoid cystic carcinoma (R/M ACC)

Intervention: Lenvatinib

recurrent/metastatic adenoid cystic carcinoma (R/M ACC)

Intervention: Pembrolizumab

recurrent/metastatic non-ACC salivary gland cancers (R/M SGC).

Intervention: Pembrolizumab

Outcomes

Primary Outcomes

best overall response rate

Time Frame: 2 years

Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)