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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06064877




Registration number
NCT06064877
Ethics application status
Date submitted
14/09/2023
Date registered
3/10/2023
Date last updated
4/06/2024

Titles & IDs
Public title
A Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV Negative Head and Neck Squamous Cell Carcinoma
Scientific title
A Multicenter, Randomized, Double Blind, Placebo - Controlled, Phase 3 Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV -Negative Head and Neck Squamous Cell Carcinoma. (FIERCE-HN)
Secondary ID [1] 0 0
AV-299-23-301
Universal Trial Number (UTN)
Trial acronym
FIERCE-HN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Head-and-neck Squamous-cell Carcinoma 0 0
Recurrent Head and Neck Squamous Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Ficlatuzumab
Other interventions - Cetuximab
Other interventions - Placebo

Experimental: Arm 1 (Investigational Arm: ficlatuzumab plus cetuximab) - Intravenous (IV) ficlatuzumab dose A on Day 1 (D1) and D15 of each 28-day cycle IV cetuximab on D1 and D15 of each 28-day cycle

Experimental: Arm 2 (Investigational Arm: ficlatuzumab plus cetuximab) - IV ficlatuzumab dose B on D1 and D15 of each 28-day cycle IV cetuximab on D1 and D15 of each 28-day cycle

Placebo Comparator: Arm 3 (Comparator Arm: placebo plus cetuximab) - IV placebo (saline, ficlatuzumab-matched) on D1 and D15 of each 28-day cycle IV cetuximab on D1 and D15 of each 28-day cycle


Other interventions: Ficlatuzumab
Ficlatuzumab (AV-299) is a humanized hepatocyte growth factor (HGF) inhibitory immunoglobulin G1 (IgG1) monoclonal antibody (mAb).

Other interventions: Cetuximab
Cetuximab is an epidermal growth factor receptor (EGFR) antagonist.

Other interventions: Placebo
Placebo for this study will be normal saline
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To compare the efficacy by overall survival of ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)
Timepoint [1] 0 0
From Randomization until death from any cause (Approximately 44 months)
Secondary outcome [1] 0 0
To evaluate additional endpoints of efficacy for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Timepoint [1] 0 0
From Randomization until disease progression or death (Approximately 44 months)
Secondary outcome [2] 0 0
To evaluate additional endpoints of efficacy for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Timepoint [2] 0 0
From Cycle 1 Day 1 until last response assessment (response assessments are every 8 weeks for the first year, every 12 weeks for years 2 and 3 and then every 6 months)
Secondary outcome [3] 0 0
To evaluate additional endpoints of efficacy for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Timepoint [3] 0 0
From Cycle 1 Day 1 until last response assessment (response assessments are every 8 weeks for the first year, every 12 weeks for years 2 and 3 and then every 6 months)
Secondary outcome [4] 0 0
To compare the safety and tolerability of ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Timepoint [4] 0 0
From Screening until 30 days after last dose
Secondary outcome [5] 0 0
To evaluate the pharmacokinetics (Pk) of ficlatuzumab and cetuximab
Timepoint [5] 0 0
From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
Secondary outcome [6] 0 0
To assess the immunogenicity of ficlatuzumab via antidrug antibodies (ADAs)
Timepoint [6] 0 0
From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
Secondary outcome [7] 0 0
To assess the immunogenicity of ficlatuzumab via neutralizing antibodies (nAB)
Timepoint [7] 0 0
From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)

Eligibility
Key inclusion criteria
- Male or female and = 18 years of age

- Histologically and/or cytologically confirmed primary diagnosis of R/M HNSCC

- Participants with oropharyngeal cancer will be required to have proof of HPV-negative
status submitted on the basis of a pathology report

- At least 1 measurable lesion by contrast CT or MRI scan according to RECIST v.1.1.
Such lesions must not have been previously irradiated; if the measurable lesion(s) has
been irradiated, clear progression must be documented

- Participants must have failed prior therapy with an anti-PD-1/PD-L1 ICI and with
platinum-based chemotherapy administered in combination or sequentially, in either the
locally advanced or R/M setting. Failure of prior treatment may be due to progression
of disease or intolerance to treatment

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with a life
expectancy of at least 12 weeks

- For women of childbearing potential (WOCBP), documentation of negative serum pregnancy
test within 30 days of randomization

- For WOCBP and male participants whose sexual partners are of childbearing potential,
agreement to use an effective method of contraception during the study and for at
least 60 days after the last dose of study treatment. Birth control methods which may
be considered highly effective include methods that achieve a failure rate of less
than 1% per year when used consistently and correctly.

- Ability to give written informed consent and comply with protocol requirements

- Patients with feeding tubes are eligible for the study.

- Archived tissue sample must be submitted to the Sponsor-designated laboratory within
60 days of randomization for c-Met/HGF analysis
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of severe allergic or anaphylactic reactions or hypersensitivity to
recombinant proteins or excipients in the investigational agent or cetuximab

- Known untreated and uncontrolled brain metastases or leptomeningeal carcinomatosis
Note: Participants with locally treated brain metastases are eligible provided 2 weeks
have elapsed since local therapy. Participants are allowed to continue steroid taper
during the start of study treatment.

- Prior treatment with any other investigational drug or biologic agent before a washout
has been completed (must be completed prior to randomization):

1. 2 weeks (14 days) or 5 half-lives, whichever is shorter, for chemotherapeutic
agents, small molecules, and checkpoint inhibitors

2. 3 weeks (21 days) or 5 half-lives, whichever is shorter, for antibody-drug
conjugates

3. 4 weeks (28 days) for cell therapies

- Any unresolved and significant toxicity (National Cancer Institute Common Terminology
Criteria for Adverse Events [NCI-CTCAE] version 5.0) Grade > 2 from previous
anticancer therapy (including radiation therapy), other than alopecia

- Significant cardiovascular disease, including: Cardiac failure New York Heart
Association class III or IV; Myocardial infarction, severe or unstable angina within 6
months prior to randomization; History of serious ventricular arrhythmia (i.e.,
ventricular tachycardia or ventricular fibrillation)

- Any other medical condition or psychiatric condition that, in the opinion of the
Investigator, might interfere with the participant's involvement in the study or
interfere with the interpretation of study results

- History of prior malignancy within 2 years prior to randomization (except for
adequately treated non-melanoma skin cancer, carcinoma in situ of the breast or
cervix, superficial bladder cancer, or early-stage prostate cancer, without evidence
of recurrence; participants may or may not be on maintenance therapy)

- Female participants who are pregnant or breastfeeding

A full list of inclusion and exclusion criteria can be found in the protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/01/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2027
Actual
Sample size
Target
410
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
St George Hospital - Kogarah
Recruitment hospital [2] 0 0
St. Vincent's Hospital - Sydney
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [4] 0 0
St. John of God Murdoch Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2010 - Sydney
Recruitment postcode(s) [3] 0 0
4102 - Brisbane
Recruitment postcode(s) [4] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Wisconsin
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Aberdeen
Country [16] 0 0
United Kingdom
State/province [16] 0 0
London
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Nottingham
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AVEO Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to compare the efficacy and safety of ficlatuzumab plus
cetuximab compared to placebo plus cetuximab in participants with recurrent/metastatic (R/M)
HPV-negative Head and Neck Cancer.

The primary hypothesis is that ficlatuzumab combined with cetuximab is superior to cetuximab
alone in terms of progression-free survival and/or overall survival.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06064877
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clinical Trials Office
Address 0 0
Country 0 0
Phone 0 0
+1.857.400.0101
Fax 0 0
Email 0 0
clinical@aveooncology.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06064877