Clinical Trials /

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

NCT03990571

Description:

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.

Related Conditions:
  • Adenoid Cystic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Axitinib and Avelumab in Treating Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma
  • Official Title: A Phase 2 Clinical Trial of Axitinib and Avelumab in Patients With Recurrent/Metastatic Adenoid Cystic Carcinoma (ACC)

Clinical Trial IDs

  • ORG STUDY ID: 2019-0107
  • SECONDARY ID: NCI-2019-03704
  • SECONDARY ID: 2019-0107
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03990571

Conditions

  • Metastatic Adenoid Cystic Carcinoma
  • Progressive Disease
  • Recurrent Adenoid Cystic Carcinoma

Interventions

DrugSynonymsArms
AvelumabBavencio, MSB-0010718C, MSB0010718CTreatment (axitinib, avelumab)
AxitinibAG-013736, AG013736, InlytaTreatment (axitinib, avelumab)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Assess the objective response rate (ORR) to axitinib and avelumab combination according to
      Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria patients with recurrent or
      metastatic adenoid cystic carcinoma (ACC) who have evidence of disease progression within 6
      months prior to study enrollment.

      SECONDARY OBJECTIVES:

      I. Assess ORR to axitinib and avelumab combination according to immune-related (ir)RECIST
      criteria patients with recurrent or metastatic adenoid cystic carcinoma (ACC).

      II. Evaluate median progression free survival (PFS), PFS rate at 6 months after start of
      treatment.

      III. Evaluate median overall survival (OS), OS rate at 6 months after start of treatment.

      IV. Evaluate duration of response (DoR). V. Evaluate safety and toxicity.

      EXPLORATORY OBJECTIVES:

      I. Assess molecular markers associated with response and resistance to the study combination
      using tissue and/or plasma obtained from study participants.

      OUTLINE:

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

      After completion of study treatment, patients are followed up at 30 and 90 days and then
      every 6 months thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (axitinib, avelumab)ExperimentalPatients 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.
  • Avelumab
  • Axitinib

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  Non-sterilized males who are sexually active with a female partner of childbearing
             potential must use adequate contraception for the duration of the study and 30 days
             after the last dose of study medication. Adequate contraception methods include: birth
             control pills (e.g. combined oral contraceptive pill), barrier protection (e.g. condom
             plus spermicide, cervical/vault cap or intrauterine device), and abstinence. Patients
             should not father a child for 6 months after completion of the study medication.
             Patients should refrain from donating sperm from the start of dosing until 6 months
             after discontinuing the study medication. If male patients wish to father children
             they should be advised to arrange for freezing of sperm samples prior to the start of
             the study medication

          -  For patients with hypertension, upon entry into study must have blood pressure of <
             140/90

          -  Corrected QT interval (QTc) < 470 msec

        Exclusion Criteria:

          -  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

          -  Patients with a baseline electrocardiography (EKG) demonstrating a QTc > 470 ms

          -  Serious non-healing or dehiscing wound, active ulcer or untreated bone fracture

          -  Proteinuria as demonstrated by urine dipstick or > 1 g of protein in a 24 hour urine
             collection. All patients with >= 2+ protein on dipstick urinalysis at baseline must
             undergo a 24 hour urine collection for protein

          -  Evidence of bleeding diathesis or clinically significant coagulopathy (in the absence
             of therapeutic anticoagulation)

          -  Other severe acute or chronic medical conditions including immune colitis,
             inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric
             conditions including recent (within the past year) or active suicidal ideation or
             behavior; or laboratory abnormalities that may increase the risk associated with study
             participation or study treatment administration or may interfere with the
             interpretation of study results and, in the judgment of the investigator, would make
             the patient inappropriate for entry into this study

          -  Subject with an uncontrolled seizure disorder, active neurologic disease, or active
             central nervous system (CNS) involvement except for individuals who have
             previously-treated CNS metastases, are asymptomatic, and have no requirement for doses
             of corticosteroids (indicated to reduce brain edema) higher than the equivalent of 10
             mg of oral prednisone a day or anti-seizure medication for at least 2 weeks prior to
             first dose of study drug

          -  History of ongoing malignancies or malignancies in remission < 2 years. Adequately
             curative intent treated initial stage non-melanoma skin cancers; in situ carcinoma of
             the cervix; breast carcinoma in situ; low-grade local bladder cancer; and low-risk
             prostate cancer undergoing active surveillance will be allowed

          -  Pregnant women are excluded from this study. Based on its mechanism of action.
             Avelumab can cause fetal harm when administered to a pregnant woman. In animal models,
             the PD-1/PD-L1 signaling pathway is important in the maintenance of pregnancy through
             induction of maternal immune tolerance to fetal tissue. Human IgG1 immunoglobulins are
             known to cross the placenta. Therefore, avelumab has the potential to be transmitted
             from the mother to the developing fetus. Blockade of PD-L1 signaling has been shown in
             murine models of pregnancy to disrupt tolerance to the fetus and to result in an
             increase in fetal loss. Therefore, potential risks of administering avelumab during
             pregnancy include increased rates of abortion or stillbirth. Advise females of
             reproductive potential to use effective contraception during treatment with avelumab
             and for at least one month after the last dose of avelumab

          -  Lactating females: There is no information regarding the presence of avelumab in human
             milk, the effects on the breastfed infant, or the effects on milk production. Since
             many drugs including antibodies are excreted in human milk, advise a lactating woman
             not to breastfeed during treatment and for at least one month after the last dose of
             avelumab due to the potential for serious adverse reactions in breastfed infants

          -  Prior treatment with immune checkpoint inhibitor (e.g. anti-PD-1/PD-L1)

          -  Prior treatment with VEGF or VEGFR inhibitors (e.g. lenvatinib, bevacizumab)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate
Time Frame:Up to 6 months
Safety Issue:
Description:Will be evaluated per Response Evaluation Criteria in Solid Tumors 1.1 criteria. The trial will be conducted by Simon's 2-stage design and the response rate will be estimated after the second stage. The response rate will be estimated along with its 95% confidence interval.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:At 6 months after start of treatment
Safety Issue:
Description:Will be estimated using the method of Kaplan and Meier.
Measure:Progression-free survival
Time Frame:At 6 months after start of treatment
Safety Issue:
Description:Will be estimated using the method of Kaplan and Meier.
Measure:Duration of response
Time Frame:Up to 3 years
Safety Issue:
Description:Will be estimated using the method of Kaplan and Meier.
Measure:Incidence of adverse events
Time Frame:Up to 4 weeks after start of study treatment
Safety Issue:
Description:Toxicity is defined as adverse events in the first 4 weeks that are judged to be attributable to one agent or both in combination.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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