NPC - AXEL Study : Axitinib-Avelumab

August 1, 2023 updated by: Edwin P Hui, Chinese University of Hong Kong

AXEL: Axitinib-Avelumab Combination in Recurrent or Metastatic Nasopharyngeal Cancer: a Multicenter Phase 2 Trial

Nasopharyngeal cancer (NPC) is the most common head and neck cancer in South China and South East Asia. Worldwide, there are 80,000 incident cases and 50,000 deaths annually. In Hong Kong, NPC ranked as the tenth most common cancer in man. Up to 30% of NPC patients will develop recurrence or metastases after primary radiotherapy or chemoradiation. Platinum-based chemotherapy regimen has been the main stay of first line treatment for recurrent or metastatic NPC. However, the duration of response is short and currently there is no recommended standard second line chemotherapy. Axitinib is a highly potent and selective inhibitor of VEGF receptor. Selectively targeting a single growth factor receptor pathway provides the potential to rationally adjust dosages and combine drugs directed at specific parts of the pathway to minimize toxicity and achieve the optimum therapeutic benefit. In the phase 2 axitinib monotherapy in recurrent or metastatic NPC who failed at least one line of chemotherapy, the clinical benefit rate (CBR, complete response + partial response + stable disease) was 78.4% at 3 months but decreased to 43.2% at 6 months. However, the confirmed objective response rate (ORR) by RECIST was only 2.7% and unconfirmed ORR of 18.9%, with no complete response.Recently, the promising clinical activity of immune check point inhibitors has been demonstrated in NPC. The ORR was 25.9% (7 partial responses out of 27 patients) for single agent pembrolizumab, and 20.5% (including 1 complete response and 7 partial responses out of 44 patients) for single agent nivolumab,9 in recurrent or metastatic NPC who failed at least first line chemotherapy.

The combination of axitinib and avelumab has been studied in renal cell carcinoma (RCC). Based on the above promising and positive results in renal cell carcinoma (RCC) and head and neck squamous cell carcinomas (HNSCC), the investigators hypothesize that the combination of axitinib and avelumab in the second line setting of NPC will achieving a more complete, deep and durable response than either agent alone, without a significant increase in toxicity.

This is an open-label, single arm, phase 2 clinical trial evaluating the activity and safety of the combination of axitinib and avelumab in recurrent or metastatic NPC patients who failed at least one line of platinum-based chemotherapy.

Study Overview

Status

Active, not recruiting

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

43

Phase

  • Phase 2

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

Study Contact Backup

Study Locations

      • Hong Kong, Hong Kong
        • Department of Clinical Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong

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

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed diagnosis of nasopharyngeal carcinoma (NPC) (either at initial diagnosis or at recurrence).
  • Available fresh or archival tumor tissue for biomarker study
  • Patients with recurrent or metastatic NPC that has progressed following one line of prior platinum-based chemotherapy.
  • Disease must be not amenable to potentially curative radiotherapy or surgery.
  • At least one measurable lesion as defined by RECIST v1.1 that has not been previously irradiated.
  • Age 18 or above;
  • ECOG performance 0 or 1.
  • Adequate bone marrow, renal and hepatic reserve.

Exclusion Criteria:

  • Prior therapy with immune check point inhibitors or VEGF pathway inhibitors.
  • Presence of local recurrence.
  • Presence of neck lymph node recurrence invading vascular structure.
  • Presence of central lung lesions involving major blood vessels.
  • History of hemoptysis or epistaxis within 4 weeks.
  • Preexisting uncontrolled hypertension defined as more than 140/90 mmHg despite adequate medical therapy.
  • Gastrointestinal abnormalities, including inability to take oral medication or malabsorption syndrome.
  • Concurrent use or anticipated need for treatment with known potent CYP3A4 inhibitors or CYP3A4 /CYP1A2 inducers.
  • CNS metastases requiring systemic steroid
  • Active autoimmune disease
  • Pregnant or lactating female

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: Axitinib and Avelumab

Axitinib: 5 mg bd po Day 1 to Day 28

Avelumab: 10mg/kg Day 1 and Day 15 every 4 weeks

Axitinib: 5 mg bd po Day 1 to Day 28
Avelumab: 10 mg/kg Day 1 to Day 15 every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Confirmed objective response rate (ORR)
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival (PFS)
Time Frame: 3 years
3 years
Overall survival (OS)
Time Frame: 3 years
3 years
6-month PFS rate
Time Frame: 6 months
6 months
OS rates at 12 months and 24 months
Time Frame: 2 years
2 years
Objective tumor response rate
Time Frame: 2 years
2 years
Disease control rate (DCR) at 12 and 24 weeks
Time Frame: 2 years
2 years
Time to tumor response (TTR)
Time Frame: 2 years
2 years
Duration of response (DR)
Time Frame: 2 years
2 years
Patient-Reported Outcomes (FACT-NP)
Time Frame: 2 years
2 years
Patient-Reported Outcomes (EQ-5D)
Time Frame: 2 years
2 years
Type, incidence, severity (graded by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0)
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Anthony Chan, MD, Department of Clinical Oncology, The Chinese 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)

May 6, 2021

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

September 14, 2020

First Submitted That Met QC Criteria

September 23, 2020

First Posted (Actual)

September 24, 2020

Study Record Updates

Last Update Posted (Actual)

August 3, 2023

Last Update Submitted That Met QC Criteria

August 1, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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.

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