- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03826589
Avelumab With Axitinib in Persistent or Recurrent Cervical Cancer After Platinum-based Chemotherapy (ALARICE)
September 30, 2023 updated by: Dr. Ka-Yu Tse, The University of Hong Kong
Avelumab With Axitinib in Persistent or Recurrent Cervical Cancer After Platinum-based Chemotherapy - a Proof-of-concept Study (ALARICE Study)
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Estimated)
23
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Ka Yu Tse
- Phone Number: 852-22554518
- Email: tseky@hku.hk
Study Locations
-
-
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Hong Kong, Hong Kong
- The University of Hong Kong
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Patients must be at least 18 years old.
- 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.
- Patients should not be amenable to further surgery or radiotherapy except for the purpose of symptomatic relief.
- Patients should have ECOG performance score 0 to 2.
- Patients must have at least one target lesion by the RECIST 1.1 criteria.
- Prior chemotherapy must have been completed at least 3 weeks before study drug administration, and all AEs have either returned to baseline or stabilized.
- 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.
- Patients must have recovered from any major surgery that has been done at least 4 weeks before study drug administration.
- Patients must have adequate bone marrow, renal, hepatic, thyroid and neurological function.
- Patients should be willing to have blood tests where the blood will be used for biomarker studies.
- 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.
- 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.
- 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:
- Patients with concurrent malignancy within five years (except for basal or squamous cell skin cancer or in-situ breast cancer) are excluded.
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.
- 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.
- 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.
- 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.
- 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.
- Patients with unhealed wounds include abdominal or pelvic fistula, gastrointestinal perforation or intra-abdominal abscess are excluded.
- 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.
- Patents with active tuberculosis, history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) are excluded.
- Patients who have suicidal ideations or behaviors requiring psychiatric intervention within 3 months prior to the start of treatment are excluded.
- 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.
- Patients who have known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the avelumab formulation.
- 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.
- 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.
- Patients who have received axitinib before are excluded.
- Patients who received other anti-angiogenics within the last 6 months are excluded.
- Patients with prior allogeneic stem cell or solid organ transplantation are excluded.
- 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.
- 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.
- Patients with major operation within 28 days or open biopsy within 7 days before enrolment are not eligible.
- Patients planned to have major surgery during the course of the study are excluded.
- Patients who are pregnant or breastfeeding are excluded.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Avelumab and Axitinib
|
an anti-programmed cell death ligand 1
Other Names:
a tyrosine kinase inhibitor that also inhibits VEGF receptor 1-3, c-KIT and PDGFR
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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Up to 2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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Up to 2 years
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Overall survival
Time Frame: Up to 2 years
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Overall survival is defined as the time from first dose of trial medication to date of death due to any cause.
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Up to 2 years
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Objective tumor response rate
Time Frame: Up to 2 years
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Objective tumor response rate according to the immune-related ResponseCriteria Derived from RECIST 1.1 (irRECIST)
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Up to 2 years
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Disease control rate at 12 weeks
Time Frame: Up to 2 years
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Disease control rate at 12 weeks including complete response (CR), partial response (PR), stable disease (SD)
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Up to 2 years
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Duration of response
Time Frame: Up to 2 years
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Duration of response and duration of clinical benefit including CR, PR and SD
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Up to 2 years
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Rates of abnormal laboratory values and/or adverse events that are related to the treatment drugs
Time Frame: Up to 2 years
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Treatment-related adverse events classified by CTCAE version 5.0 and laboratory safety assessments
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Up to 2 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Ka Yu Tse, The University of Hong Kong
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 1, 2019
Primary Completion (Estimated)
March 1, 2024
Study Completion (Estimated)
July 1, 2024
Study Registration Dates
First Submitted
January 30, 2019
First Submitted That Met QC Criteria
January 31, 2019
First Posted (Actual)
February 1, 2019
Study Record Updates
Last Update Posted (Actual)
October 3, 2023
Last Update Submitted That Met QC Criteria
September 30, 2023
Last Verified
September 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Uterine Neoplasms
- Genital Neoplasms, Female
- Uterine Cervical Diseases
- Uterine Diseases
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Uterine Cervical Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Avelumab
- Axitinib
Other Study ID Numbers
- WI224183 / UW 18-417
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
IPD Plan Description
Undecided
Drug and device information, study documents
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cervical Cancer
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University of California, San DiegoWithdrawnCervical Cancer | Cervical Cancer Stage | Cervical Cancer Stage IB2 | Cervical Cancer Stage IB1 | Cervical Cancer Stage I | Cervical Cancer Stage IB | Cervical Cancer Stage II | Cervical Cancer Stage IIa | Cervical Cancer, Stage IIB | Cervical Cancer, Stage III | Cervical Cancer Stage IIIB | Cervical Cancer... and other conditionsUnited States
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M.D. Anderson Cancer CenterWithdrawnStage IB3 Cervical Cancer FIGO 2018 | Stage II Cervical Cancer FIGO 2018 | Stage IIA Cervical Cancer FIGO 2018 | Stage IIA1 Cervical Cancer FIGO 2018 | Stage IIA2 Cervical Cancer FIGO 2018 | Stage IIB Cervical Cancer FIGO 2018 | Stage III Cervical Cancer FIGO 2018 | Stage IIIA Cervical Cancer FIGO... and other conditions
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Abramson Cancer Center of the University of PennsylvaniaWithdrawnCervical Cancer | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer
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National Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer | Stage IVB Cervical CancerUnited States
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Mayo ClinicNational Cancer Institute (NCI)RecruitingCervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma, Not Otherwise Specified | Recurrent Cervical Carcinoma | Stage IB3 Cervical Cancer FIGO 2018 | Stage II Cervical Cancer FIGO 2018 | Stage IIA Cervical Cancer FIGO 2018 | Stage IIA1 Cervical Cancer FIGO 2018 | Stage IIA2 Cervical... and other conditionsUnited States
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage IA Cervical Cancer | Stage IB Cervical Cancer | Stage IA1 Cervical Cancer | Stage IA2 Cervical Cancer | Stage IB1 Cervical Cancer | Stage IB2 Cervical Cancer | Stage IB3 Cervical CancerUnited States
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University of Southern CaliforniaNational Cancer Institute (NCI)CompletedRecurrent Cervical Cancer | Stage IVA Cervical Cancer | Stage IVB Cervical Cancer | Stage IIIA Cervical Cancer | Stage IIIB Cervical CancerUnited States
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Shanghai First Maternity and Infant HospitalNot yet recruitingCervical Cancer, Stage IIB | Cervical Cancer Stage IIIB | Cervical Cancer Stage IIIA | Cervical Cancer, Stage IVA
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Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical CancerUnited States
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Institut de Cancérologie de LorraineCompletedCervical Adenocarcinoma | Stage IB Cervical Cancer | Stage III Cervical Cancer | Stage II Cervical CancerFrance
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