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

NCT02098538 | Completed Phase 2 Results

• 1 other identifier: 13-244
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 5

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.

Conditions

Adenoid Cystic Carcinoma

Keywords

Regorafenib; 13-244

Outcome Measures

Primary Outcomes (2)

• Number of Participants Alive With and Without Disease Progression

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

  6 months

• Best Overall Response Rate

  (BOR = CR+PR) documented by RECIST v1.1 criteria

  6 months

Secondary Outcomes (1)

• Number of Participants Evaluated for Adverse Events

  1 year

Study Arms (1)

patients with adenoid cystic carcinoma

EXPERIMENTAL

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

Drug: Regorafenib

Interventions

Regorafenib DRUG

All eligible patients will receive a starting regorafenib dose of 120 mg daily taken orally for 3 weeks in a 4-week cycle. Patients for whom regorafenib dose reduction was not performed or required may have their treatment dose increased to the FDA-approved dose of 160 mg daily orally for 3 weeks in a 4-week cycle in cycle #2 or beyond (this is not mandatory). RECIST v1.1 tumor assessments will be made at baseline (CT or MRI) and then approximately every 2 cycles (or every 8 weeks (+/- 1 week)). After 10 months, imaging will be done every 3 cycles (or every 12 weeks (+/- 1 week)). Patients may remain on study until progression of disease or unacceptable toxicity

patients with adenoid cystic carcinoma

Eligibility Criteria

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

You may qualify if:

• 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 requirements:
• 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)

You may not qualify if:

• 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 digoxin.
• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Bayer: collaborator

Study Sites (5)

Memorial Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Adenoid Cystic

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Dr. Alan Ho, MD, PhD
• Organization: Memorial Sloan Kettering Cancer Center

hoa@mskcc.org

646-608-3774

Study Officials

• Alan Ho, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: March 24, 2014
• First Posted: March 28, 2014
• Study Start: March 1, 2014
• Primary Completion: November 7, 2024
• Study Completion: November 7, 2024
• Last Updated: September 10, 2025
• Results First Posted: September 10, 2025

Record last verified: 2024-11

Locations

US (5)