Regorafenib in Patients With Progressive, Recurrent/Metastatic Adenoid Cystic Carcinoma

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Brief Title

Regorafenib in Patients With Progressive, Recurrent/Metastatic Adenoid Cystic Carcinoma

Official Title

A Phase II Study of Regorafenib in Patients With Progressive, Recurrent/Metastatic Adenoid Cystic Carcinoma

Brief Summary

      Regorafenib is an oral medication that can interfere with cancer cell growth and reduce the
      growth of blood vessels around tumors. This study will help find out if regorafenib is a
      useful drug for treating patients with adenoid cystic carcinomas. Regorafenib has been
      approved by the Food and Drug Administration (FDA) for use in other cancers, but remains an
      experimental drug that has not yet been approved for use in adenoid cystic carcinoma.

      In this study, the patient will initially be treated with a dose of regorafenib that is lower
      than what the FDA approved for other cancers in an attempt to decrease the risk of side
      effects. It is possible that this lower starting dose may not be as effective as the higher
      FDA approved dose. If the patient does well with the lower dose for at least a month on
      treatment, the physician may consider increasing the dose to the FDA approved dose.

Study Phase

Phase 2

Study Type


Primary Outcome

patients alive without disease progression

Secondary Outcome



Adenoid Cystic Carcinoma



Study Arms / Comparison Groups

 patients with adenoid cystic carcinoma
Description:  This is a single-arm phase II study of patients with progressive, recurrent/metastatic adenoid cystic carcinoma (R/M ACC) treated with regorafenib.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

March 2014

Completion Date

March 2023

Primary Completion Date

March 2023

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have pathologically or cytologically confirmed adenoid cystic carcinoma.
             Cancers arising from non-salivary gland primary sites are allowed.

          -  Patients must have recurrent and/or metastatic disease not amenable to potentially
             curative surgery or radiotherapy.

          -  At least 2 weeks must have elapsed since the end of prior systemic treatment (4 weeks
             for bevacizumab- containing regimens) or radiotherapy with resolution of all
             treatment-related toxicity to NCI CTCAE Version 4.0 grade ≤1 (or tolerable grade 2) or
             back to baseline (except for alopecia, lymphopenia, or hypothyroidism). Any number of
             prior therapies for recurrent/metastatic ACC are allowed.

          -  Patients must have RECIST v1.1 measurable disease, defined as at least one lesion that
             can be accurately measured in at least one dimension (longest diameter to be recorded
             for nonnodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional
             techniques or as ≥ 10 mm with spiral CT scan.

          -  Patients must have documentation of a new or progressive lesion on a 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. Evidence of progression by RECIST criteria is not required.

          -  Patients must have archival tissue from the primary tumor or metastases available for
             correlative studies. Either a paraffin block or twenty unstained slides are
             acceptable. If twenty slides are not available, a lesser amount may be acceptable
             after discussion with the Principal Investigator, Dr. Alan L. Ho.

          -  Patients must agree to undergo biopsy of a malignant lesion. Biopsies do not need to
             be done if either the investigator or person performing the biopsy judges that no
             tumor is accessible for biopsy or that biopsy poses too great of a risk to the
             patient. Patients may also be exempt if frozen tumor tissue has been collected within
             12 months of study enrollment that the Principal Investigator deems is
             appropriate/sufficient for analysis on this protocol.

          -  Age ≥ 18 years.

          -  ECOG performance status ≤ 2 (Karnofsky ≥ 60%,).

          -  Life expectancy of at least 12 weeks (3 months) as determined by the investigator.

          -  Life expectancy of at least 12 weeks (3 months) as determined by the investigator.

          -  Subjects must be able to understand and be willing to sign the written informed
             consent form. A signed informed consent form must be appropriately obtained prior to
             the conduct of any trial-specific procedure.

          -  Adequate bone marrow, liver and renal function as assessed by the following laboratory

               -  Total bilirubin ≤ 1.5 x the upper limits of normal (ULN) Alanine aminotransferase
                  (ALT) and aspartate amino-transferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for subjects
                  with liver involvement of their cancer)

               -  Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver
                  involvement of their cancer)

               -  Lipase ≤ 1.5 x the ULN

               -  Amylase ≤ 1.5 x the ULN Serum creatinine ≤ 1.5 x the ULN or calculated creatinine
                  clearance >60 ml/min

               -  Platelet count ≥ 100,000 /mm3, hemoglobin (Hb) ≥ 9 g/dL, absolute neutrophil
                  count (ANC) ≥ 1500/mm3. Blood transfusion to meet the inclusion criteria will not
                  be allowed.

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 2 weeks prior to the start of study drug. Post-menopausal women (defined as no
             menses for at least 1 year) and surgically sterilized women are not required to
             undergo a pregnancy test.

          -  Subjects (men and women) of childbearing potential must agree to use adequate
             contraception beginning at the signing of the consent form until at least 3 months
             after the last dose of study drug. The definition of adequate contraception will be
             based on the judgment of the principal investigator or a designated associate.

          -  Subject must be able to swallow and retain oral medication.

        Exclusion Criteria:

          -  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.

        Palliative radiation to non-target lesions is also allowed.

          -  Prior use of regorafenib.

          -  Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm
             Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical management.

          -  Concurrent use of another investigational drug or device therapy (i.e., outside of
             study treatment) during, or within 4 weeks of trial entry (signing of the informed
             consent form).

          -  Concurrent use of strong CYP3A4 inhibitors (e.g. clarithromycin, grapefruit juice,
             itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, and
             voriconazole). or strong CYP3A4 inducers (e.g. rifampin, phenytoin, carbamazepine,
             phenobarbital, and St. John's Wort).

          -  Use of any herbal remedy (e.g. St. John's wort [Hypericum perforatum])

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             before start of study medication.

          -  Active or clinically significant cardiac disease including:

        Congestive heart failure - New York Heart Association (NYHA) > Class II.

          -  Active coronary artery disease that is not medically treated.

          -  Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or

          -  Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before
             randomization, or myocardial infarction within 6 months before randomization.

               -  Therapeutic anticoagulation with Vitamin-K antagonists (e.g., warfarin) is not
                  allowed if the medication dose and/or INR/PTT are not considered stable by the
                  treating physician. If the dose and/or INR/PTT are stable, therapeutic
                  anticoagulation with Vitamin-K antagonists is allowed with close monitoring.
                  Anticoagulation with heparin or heparinoids is allowed.

               -  Evidence or history of bleeding diathesis or coagulopathy.

               -  Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to
                  start of study medication.

               -  Subjects with thrombotic, embolic, venous, or arterial events, such as
                  cerebrovascular accident (including transient ischemic attacks) deep vein
                  thrombosis or pulmonary embolism within 6 months of start of study treatment.

               -  Subjects with a past or current diagnosis of another malignancy that will
                  interfere with conduct of the trial. Patients with past or current cancer
                  diagnoses other than ACC are allowed to enroll if the investigator believes it
                  will not interfere with trial conduct.

               -  Patients with phaeochromocytoma.

               -  Known history of human immunodeficiency virus (HIV) infection or current chronic
                  or active hepatitis B or C infection requiring treatment with antiviral therapy.

               -  Active infection that would impair the ability of the patient to receive study

               -  Symptomatic metastatic brain or leptomeningeal tumors (asymptomatic or treated
                  metastatic brain and leptomeningeal tumors are allowed).

               -  Presence of a non-healing wound or non-healing ulcer that is not tumor related.

               -  Renal failure requiring hemo-or peritoneal dialysis.

               -  Patients with seizure disorder requiring medication.

               -  Interstitial lung disease with ongoing signs and symptoms at the time of informed

               -  History of organ allograft (including corneal transplant).

               -  Known or suspected allergy or hypersensitivity to any of the study drugs, study
                  drug classes, or excipients of the formulations given during the course of this

               -  Any malabsorption condition.

               -  Women who are pregnant or breast-feeding.

               -  Any condition which, in the investigator's opinion, makes the subject unsuitable
                  for trial participation.

               -  Substance abuse, medical, psychological or social conditions that may interfere
                  with the subject's participation in the study or evaluation of the study results.




18 Years - N/A

Accepts Healthy Volunteers



Alan Ho, MD, PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Memorial Sloan Kettering Cancer Center



Study Sponsor

Alan Ho, MD, PhD, Principal Investigator, Memorial Sloan Kettering Cancer Center

Verification Date

April 2022