Axitinib and Avelumab in Treating Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma

NCT03990571 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2019-0107NCI-2019-03704
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well axitinib and avelumab work in treating patients with adenoid cystic carcinoma that has come back or spread to other places in the body. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving axitinib and avelumab together may help to control adenoid cystic carcinoma.

Conditions

Metastatic Adenoid Cystic Carcinoma; Progressive Disease; Recurrent Adenoid Cystic Carcinoma

Outcome Measures

Primary Outcomes (1)

• Assess the Objective Response Rate (ORR) to Axitinib and Avelumab Combination According to RECIST 1.1 Criteria.

  All eligible patients who received at least one cycle of treatment and had at least one restaging image were considered evaluable for the primary end point. Objective response includes complete response (CR) + partial response (PR). Radiographic imaging for tumor assessment was performed at baseline and then every 8 weeks.

  Up to 33 months

Secondary Outcomes (4)

• Estimate Median Progression-free Survival, Median Overall Survival

  up to 40 months

• Estimate Progression Free Survival Rate at 6 Months After Start of Treatment, Overall Survival Rate 6 Months After Start of Treatment

  completed at 6 months from start of treatment

• Estimate Duration of Response

  Up to 30 months

• Evaluate Safety and Toxicity

  Up to 30 months

Study Arms (1)

Treatment (axitinib, avelumab)

EXPERIMENTAL

Patients receive axitinib PO BID on days 1-28 and avelumab IV over 1 hour on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Avelumab; Drug: Axitinib

Interventions

Avelumab DRUG

Given IV

Also known as: Bavencio, MSB-0010718C, MSB0010718C

Treatment (axitinib, avelumab)

Axitinib DRUG

Given PO

Also known as: AG-013736, AG013736, Inlyta

Treatment (axitinib, avelumab)

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group ECOG performance status 0 or 1
• Histologically confirmed recurrent or metastatic adenoid cystic carcinoma not amenable to curative intent surgery or radiotherapy
• Measurable disease per RECIST 1.1
• Evidence of disease progression within 6 months of study enrollment or worsening disease-related symptoms
• Previously untreated subjects and subject treated with any number of prior lines of therapy are eligible
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Platelet count \>= 100 x 10\^9/L
• Hemoglobin \>= 9 g/dL (may have been transfused)
• Total bilirubin level =\< 1.5 x the upper limit of normal (ULN) range
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =\< 2.5 x ULN or AST and ALT levels =\< 5 x ULN (for subjects with documented metastatic disease to the liver)
• Estimated creatinine clearance \>= 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
• Must have archival tissue (formalin-fixed, paraffin-embedded \[FFPE\] tissue available-minimum of 15 unstained slides) or be willing to undergo a biopsy
• For patients receiving anti-therapeutic coagulation, patients must be on stable anticoagulant regimen and international normalized ratio (INR) or activated partial thromboplastin time (aPTT) must be =\< 1.5 upper limit of normal
• Females of childbearing potential must not be breast feeding and must have a negative serum or urine pregnancy test and must agree to use highly effective contraception for a minimum of two weeks prior to receiving study medication until 30 days after discontinuation of the study medication. Acceptable methods of contraception include total and true sexual abstinence, hormonal contraceptives that are not prone to drug-drug interactions (intra uterine system \[IUS\] levonorgestrel intra uterine system \[Mirena\], medroxyprogesterone injections \[Depo-Provera\]), copper-banded intra-uterine devices, and vasectomized partner. All hormonal methods of contraception should be used in combination with the use of a condom by their sexual male partner. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause)
• Women will be considered post-menopausal if they have been amenorrheic for the past 12 months without an alternative medical cause. The following age-specific requirements must also apply: Women \< 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of exogenous hormonal treatments. The levels of luteinizing hormone (LH) and follicle-stimulating Hormone (FSH) must also be in the post menopausal range (as per the institution). Women \>= 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of all exogenous hormonal treatments, or have had radiation-induced oophorectomy with the last menses \> 1 year ago, or have had chemotherapy-induced menopause with \> 1 year interval since last menses, or have had surgical sterilization by either bilateral oophorectomy or hysterectomy

You may not qualify if:

• Current use of immunosuppressive medication, EXCEPT for the following:
• Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
• Systemic corticosteroids at physiologic doses =\< 10 mg/day of prednisone or equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., computed tomography \[CT\] scan premedication)
• Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible
• Prior organ transplantation including allogenic stem-cell transplantation
• Active infection requiring systemic therapy
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV ribonucleic acid \[RNA\] if anti-HCV antibody screening test positive)
• Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines
• Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]4.03 grade \>= 3)
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (\>= New York Heart Association Classification class II), or serious cardiac arrhythmia requiring medication
• Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 grade \> 1); however, alopecia, sensory neuropathy grade =\< 2, or other grade =\< 2 not constituting a safety risk based on investigator's judgment are acceptable
• Inadequately controlled hypertension (defined as systolic blood pressure \> 140 mmHg and/or diastolic blood pressure \> 90 mmHg). Anti-hypertensive therapy to maintain a systolic blood pressure \< 140 mmHg and/or diastolic blood pressure \< 90 mmHg is permitted
• Prior history of hypertensive crisis or hypertensive encephalopathy

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Ferrarotto R, Sousa LG, Feng L, Mott F, Blumenschein G, Altan M, Bell D, Bonini F, Li K, Marques-Piubelli ML, Dal Lago EA, Johnson JJ, Mitani Y, Godoy M, Lee A, Kupferman M, Hanna E, Glisson BS, Elamin Y, El-Naggar A. Phase II Clinical Trial of Axitinib and Avelumab in Patients With Recurrent/Metastatic Adenoid Cystic Carcinoma. J Clin Oncol. 2023 May 20;41(15):2843-2851. doi: 10.1200/JCO.22.02221. Epub 2023 Mar 10.

  PMID: 36898078 DERIVED

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Adenoid Cystic; Disease Progression

Interventions

avelumab; Axitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Renata Ferrarotto
• Organization: The University of Texas M D Anderson Cancer Center

rferrarotto@mdanderson.org

(713) 745-6774

Study Officials

• Renata Ferrarotto

  M.D. Anderson 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: June 17, 2019
• First Posted: June 19, 2019
• Study Start: July 22, 2019
• Primary Completion: March 20, 2023
• Study Completion: March 20, 2023
• Last Updated: October 18, 2024
• Results First Posted: August 26, 2024

Record last verified: 2024-07

Locations

US (1)