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Avelumab With Axitinib in Persistent or Recurrent Cervical Cancer After Platinum-based Chemotherapy (ALARICE)

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ClinicalTrials.gov Identifier: NCT03826589
Recruitment Status : Recruiting
First Posted : February 1, 2019
Last Update Posted : February 18, 2020
Sponsor:
Information provided by (Responsible Party):
Dr. Ka-Yu Tse, The University of Hong Kong

Brief Summary:
This is a single-arm, Simon's 2-stage, proof-of-concept trial. The aim is to evaluate the efficacy and safety of avelumab with axitinib in patients with persistent or recurrent cervical cancer following platinum-based chemotherapy. The study hypothesis is that the combination of avelumab and axitinib can significantly improve the objective response rate (ORR) with acceptable toxicity compared to traditional chemotherapy.

Condition or disease Intervention/treatment Phase
Cervical Cancer Drug: Avelumab Drug: Axitinib Not Applicable

Detailed Description:
Cervical cancer is the fourth commonest female cancer in the world. When there is distant metastasis or recurrence, platinum-based chemotherapy is the usual treatment option. Once this first-line chemotherapy fails, the prognosis is dismal. Various second-line agents including second-line chemotherapy agents and immune checkpoint inhibitors have unsatisfactory response rate.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 23 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Avelumab With Axitinib in Persistent or Recurrent Cervical Cancer After Platinum-based Chemotherapy - a Proof-of-concept Study (ALARICE Study)
Actual Study Start Date : June 1, 2019
Estimated Primary Completion Date : March 1, 2024
Estimated Study Completion Date : July 1, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cervical Cancer

Arm Intervention/treatment
Experimental: Avelumab and Axitinib
  • Avelumab: IV treatment; administered at 10 mg/kg IV every two weeks in a 4-weekly cycle up to 12 cycles or until disease progression or intolerable side effects (whichever occurs first)
  • Axitinib: Oral treatment; administered at 5 mg PO BID in a 4-weekly cycle up to 12 cycles or until disease progression or intolerable side effects (whichever occurs first)
Drug: Avelumab
an anti-programmed cell death ligand 1
Other Name: Bavencio

Drug: Axitinib
a tyrosine kinase inhibitor that also inhibits VEGF receptor 1-3, c-KIT and PDGFR
Other Name: Inlyta




Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: Up to 2 years ]
    ORR is defined as the proportion of patients who have a CR or PR to the study drugs.


Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Up to 2 years ]
    The time from first dose of trial medication to first documentation of objective tumor progression (PD) or to death due to any cause, whichever occurs first.

  2. Overall survival [ Time Frame: Up to 2 years ]
    Overall survival is defined as the time from first dose of trial medication to date of death due to any cause.

  3. Objective tumor response rate [ Time Frame: Up to 2 years ]
    Objective tumor response rate according to the immune-related ResponseCriteria Derived from RECIST 1.1 (irRECIST)

  4. Disease control rate at 12 weeks [ Time Frame: Up to 2 years ]
    Disease control rate at 12 weeks including complete response (CR), partial response (PR), stable disease (SD)

  5. Duration of response [ Time Frame: Up to 2 years ]
    Duration of response and duration of clinical benefit including CR, PR and SD

  6. Rates of abnormal laboratory values and/or adverse events that are related to the treatment drugs [ Time Frame: Up to 2 years ]
    Treatment-related adverse events classified by CTCAE version 5.0 and laboratory safety assessments



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must be at least 18 years old.
  2. Patients must have histologically confirmed cervical cancer, either squamous cell, adenocarcinoma or adenosquamous, that is either persistent or recurrent after at least one prior course of platinum-based chemotherapy. The platinum used in concurrent chemo-irradiation is not counted.
  3. Patients should not be amenable to further surgery or radiotherapy except for the purpose of symptomatic relief.
  4. Patients should have ECOG performance score 0 to 2.
  5. Patients must have at least one target lesion by the RECIST 1.1 criteria.
  6. Prior chemotherapy must have been completed at least 3 weeks before study drug administration, and all AEs have either returned to baseline or stabilized.
  7. Prior systemic radiation therapy must have been completed at least 4 weeks before study drug administration. Prior focal radiotherapy must have completed at least 2 weeks before study drug administration.
  8. Patients must have recovered from any major surgery that has been done at least 4 weeks before study drug administration.
  9. Patients must have adequate bone marrow, renal, hepatic, thyroid and neurological function.
  10. Patients should be willing to have blood tests where the blood will be used for biomarker studies.
  11. Formalin-fixed, paraffin-embedded (FFPE) archival tumor specimens of the primary tumors, should be available during screening. Alternatively, 15 unstained slides (6 minimum) will be acceptable.
  12. Patients should agree for de novo biopsy if the tumors are at the cervix or vagina, or any other sites that are easy and safe to be biopsied. Tumors will be used for biomarker studies.
  13. Patients who have childbearing potential should practice highly effective contraception throughout the study until at least 30 days after completion of the treatment

Exclusion Criteria:

  1. Patients with concurrent malignancy within five years (except for basal or squamous cell skin cancer or in-situ breast cancer) are excluded.
  2. Patients who have history of autoimmune diseases or other diseases requiring systemic steroid are excluded.

    Patients with vitiligo, type I diabetes mellitus, resolved asthma or atopy, stable autoimmune thyroid disease, eczema, psoriasis not requiring systemic treatment*, or not expected to recur in the absence of an external trigger are permitted to enroll.

  3. Patients with the following past significant medical history in the last six months are excluded, such as pneumonitis, active or chronic viral hepatitis, cirrhosis, and inherited liver disease, myocardial infarction, unstable angina, unstable cardiac arrhythmia or clinically significant valvular heart diseases, CTCAE Grade 2 or greater peripheral vascular disease, active brain metastases or leptomeningeal metastases, uncontrolled seizures, subarachnoid hemorrhage, thromboembolic events.
  4. Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days of the start of treatment are excluded. Inhaled, local or topical steroids, systemic corticosteroids at physiologic doses, steroid used as pre-medication are allowed.
  5. Patients with severe gastrointestinal conditions such as evidence of bowel obstruction or uncontrolled diarrhea in the last 4 weeks prior to enrollment, or history of inflammatory bowel disease, are not eligible.
  6. Patients with uncontrolled hypertension (systolic >160mmHg or diastolic > 110mmHg) despite medication, active bleeding, bone fracture, unhealed wounds, clinically significant proteinuria (> 2g of protein over 24 hours), are excluded.
  7. Patients with unhealed wounds include abdominal or pelvic fistula, gastrointestinal perforation or intra-abdominal abscess are excluded.
  8. Patients having had severe infections within 4 weeks prior to the start of treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, and those who have active infection requiring systematic treatment, are excluded.
  9. Patents with active tuberculosis, history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) are excluded.
  10. Patients who have suicidal ideations or behaviors requiring psychiatric intervention within 3 months prior to the start of treatment are excluded.
  11. Patients who have history of severe (CTCAE Grade 3 or above) hypersensitivity reaction to any investigational products or any component in its formulations, and any monoclonal antibody, are excluded.
  12. Patients who have known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the avelumab formulation.
  13. Patients who have persisting toxicities related to previous therapy (NCI CTCAE v 5.0 Grade >1) are excluded. However, alopecia, Grade 2 or less sensory neuropathy, or other toxicities of Grade 2 or below that do not constitute a safety risk according to the investigators' judgment, are allowed.
  14. Patients who have received prior immunotherapy, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, are excluded.
  15. Patients who have received axitinib before are excluded.
  16. Patients who received other anti-angiogenics within the last 6 months are excluded.
  17. Patients with prior allogeneic stem cell or solid organ transplantation are excluded.
  18. Use of other investigational drugs (drugs not marketed for any indication) within 28 days or at least 5 half-lives (whichever is longer) before the start of treatment, or during the course of this trial, is not allowed.
  19. Use of any live attenuated vaccines against infectious diseases (e.g. influenza, varicella, etc.) within 4 weeks (28 days) of the start of treatment and during the study therapy is not allowed.
  20. Patients with major operation within 28 days or open biopsy within 7 days before enrolment are not eligible.
  21. Patients planned to have major surgery during the course of the study are excluded.
  22. Patients who are pregnant or breastfeeding are excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03826589


Contacts
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Contact: Ka Yu Tse 852-22554518 tseky@hku.hk
Contact: Tina Wei 852-22554265 tinawei@hku.hk

Locations
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Hong Kong
The University of Hong Kong Recruiting
Hong Kong, Hong Kong
Contact: Ka Yu Tse    852-22554518    tseky@hku.hk   
Contact: Lesley Lau    852-22554265    lsk382@hku.hk   
Sponsors and Collaborators
The University of Hong Kong
Investigators
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Principal Investigator: Ka Yu Tse The University of Hong Kong
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Responsible Party: Dr. Ka-Yu Tse, Clinical Associate Professor, The University of Hong Kong
ClinicalTrials.gov Identifier: NCT03826589    
Other Study ID Numbers: WI224183 / UW 18-417
First Posted: February 1, 2019    Key Record Dates
Last Update Posted: February 18, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Dr. Ka-Yu Tse, The University of Hong Kong:
Cervical cancer
Avelumab
Axitinib
Additional relevant MeSH terms:
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Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Axitinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action