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

  • STATUS
    Recruiting
  • End date
    Jul 1, 2024
  • participants needed
    23
  • sponsor
    The University of Hong Kong
Updated on 14 March 2022
cancer
adenocarcinoma
platinum-based chemotherapy
recurrent cervical cancer

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.

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.

Details
Condition Cervical Cancer
Treatment Avelumab, Axitinib
Clinical Study IdentifierNCT03826589
SponsorThe University of Hong Kong
Last Modified on14 March 2022

Eligibility

Yes No Not Sure

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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note