A pilot study on personalized medicine for patients with recurrent or metastatic head and neck cancer

Phase 1

• Conditions: Recurrent/metastatic squamous cell carcinoma of the head and neck; MedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-000086-74-IT
• Lead Sponsor: EORTC AISBL/IVZW

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-17
• Last Update Posted: 2 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 340

Inclusion Criteria

1- General inclusion criteria

• Histologically confirmed recurrent and/or metastatic SCCHN of the oral cavity, oropharynx, hypopharynx or larynx not amenable to curative treatment.
• At least one measurable lesion by MRI or CT-scan according to RECIST 1.1, evaluated within 2 weeks prior to registration.
• Progressive disease after first line platinum-based chemotherapy with or without cetuximab given as palliative treatment or progressive disease within 1 year if platinum-based chemotherapy was given as a part of the multimodal curative treatment.
• ECOG performance status 0 -1.
• Tumor core biopsy from any accessible tumor site available for central testing.
• Patients must have adequate organ function, evaluated within 14 days prior to cohort allocation:
• Hemoglobin = 9 g/100 ml,
• Neutrophils = 1,500/mm3,
• Platelets = 100,000/mm3,
• Total bilirubin <1.5 time the upper limit of normal (ULN) (< 3 time the upper limit of normal for Gilbert’s disease),
• Serum ALT and AST < 1.5 x ULN for age,
• Creatinine clearance > 45ml / min using the Cockcroft and Gault formula,
• International Normalized Ratio (INR) or Prothrombin Time (PT) must be within the normal ranges as per institution's standard. A window of 5% is allowed.
• Patients receiving prophylactic/short-term low molecular weight heparin are allowed to participate as long as the PT/INR values are within the expected target range of their current dose.
• Clinically normal cardiac function based on -left ventricular ejection fraction (= 50%) as assessed either by multi-gated acquisition scan or cardiac ultrasound and 12 lead ECG without clinically relevant abnormalities.
• Patients = 18 years old and must be able to give written informed consent.
• Women of child-bearing potential must have a negative pregnancy test.
• Patients of childbearing / reproductive potential must agree to use highly effective methods of contraception based on the Clinical Trial Facilitation Group (CTFG) guidance as of registration and up to 6 months after the last treatment dose.
• Female subjects who are breast feeding should agree to discontinue nursing prior to the first dose of study treatment and up to 6 months after the last study treatment.
• Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion Criteria

1 - General exclusion criteria

• Unresolved and significant toxicity CTCAE version 4.03 grade = 2 from previous anticancer therapy other than alopecia.
• History of any of the following cardiovascular conditions within 6 months prior to registration:
• myocardial infarction,
• severe/unstable angina,
• ongoing cardiac dysrhythmias of CTCAE version 4.03 Grade 2 or more,
• atrial fibrillation of any grade,
• coronary/peripheral artery bypass graft,
• symptomatic congestive heart failure according to NYHA Class III or Class IV,
• Significant active cardiac disease including uncontrolled high blood pressure according to the CTCAE v 4.03 grade 3.
• Cerebrovascular accident including transient ischemic attack and thromboembolic event like symptomatic pulmonary embolism.
• Nasopharynx and sino-nasal tumor.
• Surgery or investigational drugs or chemotherapy or other anticancer therapy within 4w before registration. Curative radiation therapy (60-70 Gy) within 8w of registration. Palliative radiation therapy will be allowed.
• Known untreated and uncontrolled brain metastases or carcinomatous meningitis.
• Known diagnosis of immune deficiency or a known history of HIV (HIV 1/2 antibodies).
• Known active Hepatitis B or Hepatitis C or pre-existing liver cirrhosis.
• Known pre-existing ILD.
• Other uncontrolled active illnesses.
• Any psychiatric, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
• Any malignancy (other than SCCHN, non-melanoma skin cancer or localized cervical cancer or localized and presumed cured prostatic cancer or basal cell carcinoma of the skin and carcinoma in situ of the cervix or bladder) within the last 3 years prior to registration.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of molecular targeted drugs or immunotherapy in patients with non-curable recurrent/metastatic SCCHN harboring pre-defined biomarkers.;Secondary Objective: • To evaluate the feasibility of a biomarker-driven trial in recurrent/metastatic SCCHN that will utilize a central biomarker screening platform to integrate genomic and proteomic testing in the clinical setting<br>• To determine the safety profile of targeted drugs/immunotherapy in patients with SCCHN (adverse events according to CTCAE version 4.03)<br>• To further investigate activity and efficacy of each compound;Primary end point(s): Depending on the patient cohort<br>1 - cohorts I1: objective response rate (ORR) according to RECIST 1.1<br>2 - cohort B1 to B3: progression free survival rate (PFSR) at 16 weeks;Timepoint(s) of evaluation of this end point: Depending on the patient cohort<br>1 - cohorts I1: every 8 weeks<br>2 - cohort B1 to B3: at 16 weeks.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1 - The percentage of patients included in each patient cohort according the biomarker testing (number of patients included/number of patients screened).<br>2 - Description of the genetic abnormalities of the screened population<br>3 - The percentage of patients with an evaluable fresh tumor biopsy<br>4 - Progression free survival<br>5 - Objective response rate according to RECIST 1.1, if not primary endpoint<br>6 - Response duration<br>7 - Objective response rate according to iRECIST (for immunotherapy patient cohort)<br>8 - Toxicity according CTCAE version 4.03<br>9 - Overall survival;Timepoint(s) of evaluation of this end point: 1 - at randomization/treatment allocation<br>2 - at randomization/treatment allocation<br>3 - at randomization/treatment allocation<br>4 - every 8 weeks<br>5 - every 8 weeks<br>6 - every 8 weeks<br>7 - at 6 months<br>8 - every 8 weeks<br>9 - every 8 weeks