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

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ClinicalTrials.gov Identifier: NCT03990571
Recruitment Status : Recruiting
First Posted : June 19, 2019
Last Update Posted : August 6, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE June 17, 2019
First Posted Date  ICMJE June 19, 2019
Last Update Posted Date August 6, 2019
Actual Study Start Date  ICMJE July 22, 2019
Estimated Primary Completion Date December 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2019)
Overall response rate [ Time Frame: Up to 6 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2019)
  • Overall survival [ Time Frame: At 6 months after start of treatment ]
    Will be estimated using the method of Kaplan and Meier.
  • Progression-free survival [ Time Frame: At 6 months after start of treatment ]
    Will be estimated using the method of Kaplan and Meier.
  • Duration of response [ Time Frame: Up to 3 years ]
    Will be estimated using the method of Kaplan and Meier.
  • Incidence of adverse events [ Time Frame: Up to 4 weeks after start of study treatment ]
    Toxicity is defined as adverse events in the first 4 weeks that are judged to be attributable to one agent or both in combination.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Axitinib and Avelumab in Treating Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma
Official Title  ICMJE A Phase 2 Clinical Trial of Axitinib and Avelumab in Patients With Recurrent/Metastatic Adenoid Cystic Carcinoma (ACC)
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Adenoid Cystic Carcinoma
  • Progressive Disease
  • Recurrent Adenoid Cystic Carcinoma
Intervention  ICMJE
  • Drug: Avelumab
    Given IV
    Other Names:
    • Bavencio
    • MSB-0010718C
    • MSB0010718C
  • Drug: Axitinib
    Given PO
    Other Names:
    • AG-013736
    • AG013736
    • Inlyta
Study Arms  ICMJE Experimental: Treatment (axitinib, avelumab)
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.
Interventions:
  • Drug: Avelumab
  • Drug: Axitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 17, 2019)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2022
Estimated Primary Completion Date December 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Renata Ferrarotto 713-745-6774 rferrarotto@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03990571
Other Study ID Numbers  ICMJE 2019-0107
NCI-2019-03704 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2019-0107 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Renata Ferrarotto M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP