Authorised Therapeutic confirmatory (Phase III) Head and Neck Squamous Cell Carcinoma (HNSCC)

A phase 3 study to look at the effects of 2 treatments used together (ficlatuzumab and cetuximab) on the overall survival of adults with a certain type of head and neck cancer (called HPV-negative) that has come back or spread to another part of the body.

EU CTIS ID: 2023-505606-42-00

What this study is testing

To compare the efficacy by overall survival (OS) of ficlatuzumab plus cetuximab versus placebo plus cetuximab in participants with recurrent or metastatic (R/M) human papilloma virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC)

Therapeutic confirmatory (Phase III)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1. Male or female and ≥ 18 years of age
8. Clinical laboratory values meeting the following criteria prior to randomization: a. Serum creatinine clearance > 30 mL/min, using Cockcroft and Gault formula b. Total bilirubin ≤ 1.5 × upper limit of normal (ULN;< 3 × ULN for Gilbert’s disease) c. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN, or AST and ALT ≤ 5 × ULN if there are liver metastases d. Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN and prothrombin time/international normalized ratio (PT/INR) ≤ 1.5 × ULN if not on anticoagulation therapy. Participants receiving anticoagulation therapy with an agent such as warfarin, low–molecular weight heparin, or a direct oral anticoagulant (DOAC) may be allowed to participate if the participant is on a stable (≥ 2 weeks) dose of anticoagulant and coagulation test results are in the therapeutic range established prior to initiation of study treatment e. Hematologic function: i. Absolute neutrophil count (ANC) ≥ 1200 cells/μL ii. Hemoglobin (Hgb) ≥ 9 g/dL or 5.6 mmol/L. (Note: The use of transfusion or other intervention to achieve Hgb ≥ 9.0 g/dL is acceptable) iii. Platelet count ≥ 75,000/μL
9. For WOCBP, documentation of negative serum pregnancy test within 30 days of randomization
10. 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 5 months after the last dose of study treatment. Birth control methods that may be considered highly effective include methods that achieve a failure rate of less than 1% per year when used consistently and correctly.
6. The patient’s tumor is considered inoperable and incurable in the opinion of the Investigator.
11. Ability to give written informed consent and comply with protocol requirements

You likely can't join if

1. Participants who have received >2 prior lines of anticancer therapy or prior treatment with cetuximab/alternative EGFR inhibitors for the treatment of R/M HNSCC a. Cetuximab/EGFR inhibitors in the adjuvant setting are not allowed b. Cetuximab/EGFR inhibitors for the treatment of locally advanced HNSCC is allowed as long as disease recurrence was at least 6 months after the completion of cetuximab/EGFR treatment. c. Participants who progressed within 6 months after treatment with a platinum-based therapy for HNSCC will be considered to have received 1 prior line of treatment for R/M HNSCC.
4. Known or suspected untreated and uncontrolled brain metastases or leptomeningeal carcinomatosis Note: Participants with a history of brain metastases or with suspected brain metastases at Screening must have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry. Participants with locally treated brain metastases are eligible provided 2 weeks have elapsed since local therapy. Any neurologic symptoms that developed either because of brain metastases or their treatment must have resolved or be either stable without the use of steroids or stable on a steroid dose of ≤ 10 mg/day of prednisone or its equivalent. Participants are allowed to continue steroid taper during the start of study treatment.
5. Prior treatment with any other investigational drug or biologic agentor, or radiation therapy before a washout has been completed (must be completed prior to randomization): a. 2 weeks (14 days) or 5 half-lives, whichever is shorter, for chemotherapeutic agents, small molecules, and checkpoint inhibitors b. 3 weeks (21 days) or 5 half-lives, whichever is shorter, for antibody-drug conjugates c. 4 weeks (28 days) for cell therapiesd. d. 2 weeks (14 days) for radiation therapy
6. 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
7. Active tumor-related bleeding within the last 30 days that is clinically significant in the opinion of the investigator
8. Significant cardiovascular disease, including: a. Echocardiogram (ECHO) showing left ventricular ejection fraction of less than 45% b. Cardiac failure New York Heart Association class III or IV c. Myocardial infarction, severe or unstable angina within 6 months prior to randomization d. History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) e. Significant thrombotic or embolic events within 3 months prior to randomization (significant thrombotic or embolic events include, but are not limited to, stroke or transient ischemic attack). Participants with catheter-related thrombosis, asymptomatic deep vein thrombosis, or asymptomatic pulmonary embolism are not excluded f. Any uncontrolled or severe cardiovascular disease, such as uncontrolled high blood pressure, in the opinion of the investigator

See the full eligibility criteria

Who can join

1. Male or female and ≥ 18 years of age
8. Clinical laboratory values meeting the following criteria prior to randomization: a. Serum creatinine clearance > 30 mL/min, using Cockcroft and Gault formula b. Total bilirubin ≤ 1.5 × upper limit of normal (ULN;< 3 × ULN for Gilbert’s disease) c. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN, or AST and ALT ≤ 5 × ULN if there are liver metastases d. Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN and prothrombin time/international normalized ratio (PT/INR) ≤ 1.5 × ULN if not on anticoagulation therapy. Participants receiving anticoagulation therapy with an agent such as warfarin, low–molecular weight heparin, or a direct oral anticoagulant (DOAC) may be allowed to participate if the participant is on a stable (≥ 2 weeks) dose of anticoagulant and coagulation test results are in the therapeutic range established prior to initiation of study treatment e. Hematologic function: i. Absolute neutrophil count (ANC) ≥ 1200 cells/μL ii. Hemoglobin (Hgb) ≥ 9 g/dL or 5.6 mmol/L. (Note: The use of transfusion or other intervention to achieve Hgb ≥ 9.0 g/dL is acceptable) iii. Platelet count ≥ 75,000/μL
9. For WOCBP, documentation of negative serum pregnancy test within 30 days of randomization
10. 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 5 months after the last dose of study treatment. Birth control methods that may be considered highly effective include methods that achieve a failure rate of less than 1% per year when used consistently and correctly.
6. The patient’s tumor is considered inoperable and incurable in the opinion of the Investigator.
11. Ability to give written informed consent and comply with protocol requirements
12. Patients with feeding tubes are eligible for the study.
13. Archived tissue sample must be submitted to the Sponsor-designated laboratory within 60 daysof randomization for c-Met analysis a. If a tissue sample is not available, the reason should be clearly documented, and a fresh biopsy may be required prior to enrollment after discussion with the Medical Monitor
2. Histologically and/or cytologically confirmed primary diagnosis of R/M HNSCC a. Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx
3. Participants with oropharyngeal cancer will be required to have proof of p16 negative status submitted on the basis of a pathology report. Equivocal/uncertain test status will not be allowed on trial. a. If p16 status is not known, it is recommended that sites use archived tissue for p16 analysis in participants with oropharyngeal cancer. A report of this analysis must be submitted to confirm eligibility for the study. Note: Per CAP guidelines, p16 positivity is declared when there is at least 70% nuclear and cytoplasmic expression of p16 with at least moderate to strong intensity (Lewis 2018).
4. At least 1 measurable lesion by contrast computed tomography (CT) or magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria in Solid Tumors Version 1.1 (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
5. 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 (if treatment failure was due to intolerance, the patient must have experienced documented progression of disease since the cessation of prior therapy)
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 with a life expectancy of at least 12 weeks

What rules you out

1. Participants who have received >2 prior lines of anticancer therapy or prior treatment with cetuximab/alternative EGFR inhibitors for the treatment of R/M HNSCC a. Cetuximab/EGFR inhibitors in the adjuvant setting are not allowed b. Cetuximab/EGFR inhibitors for the treatment of locally advanced HNSCC is allowed as long as disease recurrence was at least 6 months after the completion of cetuximab/EGFR treatment. c. Participants who progressed within 6 months after treatment with a platinum-based therapy for HNSCC will be considered to have received 1 prior line of treatment for R/M HNSCC.
4. Known or suspected untreated and uncontrolled brain metastases or leptomeningeal carcinomatosis Note: Participants with a history of brain metastases or with suspected brain metastases at Screening must have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry. Participants with locally treated brain metastases are eligible provided 2 weeks have elapsed since local therapy. Any neurologic symptoms that developed either because of brain metastases or their treatment must have resolved or be either stable without the use of steroids or stable on a steroid dose of ≤ 10 mg/day of prednisone or its equivalent. Participants are allowed to continue steroid taper during the start of study treatment.
5. Prior treatment with any other investigational drug or biologic agentor, or radiation therapy before a washout has been completed (must be completed prior to randomization): a. 2 weeks (14 days) or 5 half-lives, whichever is shorter, for chemotherapeutic agents, small molecules, and checkpoint inhibitors b. 3 weeks (21 days) or 5 half-lives, whichever is shorter, for antibody-drug conjugates c. 4 weeks (28 days) for cell therapiesd. d. 2 weeks (14 days) for radiation therapy
6. 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
7. Active tumor-related bleeding within the last 30 days that is clinically significant in the opinion of the investigator
8. Significant cardiovascular disease, including: a. Echocardiogram (ECHO) showing left ventricular ejection fraction of less than 45% b. Cardiac failure New York Heart Association class III or IV c. Myocardial infarction, severe or unstable angina within 6 months prior to randomization d. History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) e. Significant thrombotic or embolic events within 3 months prior to randomization (significant thrombotic or embolic events include, but are not limited to, stroke or transient ischemic attack). Participants with catheter-related thrombosis, asymptomatic deep vein thrombosis, or asymptomatic pulmonary embolism are not excluded f. Any uncontrolled or severe cardiovascular disease, such as uncontrolled high blood pressure, in the opinion of the investigator
9. 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
13. Treatment with any live or attenuated vaccine within 30 days prior to the first dose of study therapy.
14. Participants who are positive for hepatitis B virus (HBV) or hepatitis C virus (HCV) with indication of acute or chronic hepatitis, as follows: a. Participants who are positive for hepatitis B surface antigen (HBsAg; indicative of chronic HBV or recent acute HBV) are not eligible. b. Participants who are negative for HBsAg and positive for hepatitis B core antibody should undergo assessment of HBV DNA by polymerase chain reaction (PCR); detectable hepatitis B virus DNA suggests occult hepatitis B and warrants exclusion c. Participants who are positive for HCV virus antibody (HCVAb) should undergo assessment of HCV RNA by PCR; detectable HCV RNA suggests chronic HCV and warrants exclusion.
10. 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)
11. Major surgery within 2 weeks prior to randomization. This is defined as any surgery involving general anesthesia and ≥ 48 hours of hospital convalescence, or surgery requiring ≥ 2 weeks for recovery. Participants must be fully recovered from surgery. Surgical procedures for placement of an IV shunt are not excluded
12. Serious and/or symptomatic active infection within 14 days prior to first dose of study drug. Participants who have asymptomatic or mild infection and are currently taking a short course of antibiotics (eg, urinary tract infection, bronchitis) may be allowed after discussion with the Medical Monitor
15. Participants on immune-suppressive therapy for organ transplant or participants with a history of genetic or acquired immune suppression disease such as HIV, except: a. Participants with HIV are eligible who have cluster of differentiation 4 (CD4+) T-cell counts > 350 cells/μL without a history of AIDS-defining opportunistic infections; have been on established antiretroviral therapy that does not include a cytochrome P450 3A4 inducer for at least 4 weeks; and have an HIV viral load less than 400 copies/mL
16. Radiographic evidence (historical or at Screening) of ILD or idiopathic pulmonary fibrosis
17. Female participants who are pregnant or breastfeeding
2. Participants with nasopharyngeal cancer or paranasal sinus cancer
3. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent or cetuximab

The study team makes the final eligibility decision.

Where it's taking place

Taiwan
Korea, Republic of
United Kingdom
United States
Australia
Canada
Serbia

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Taiwan; Korea, Republic of; United Kingdom; United States; Australia; Canada and 1 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.