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-GB
• Lead Sponsor: European Organisation for Research and Treatment of Cancer

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-09-28
• Last Update Posted: 3 November 2020

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.
• Squamous cell carcinoma in cervical nodes with unknown primary are
allowed if p16-positive
• 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 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. Patients ineligible for platinum-therapy
and pre-treated with anti-PD1/PD-L1 are allowed.
• ECOG performance status 0-1 with a life expectancy of at least 12 weeks.
• Tumor core biopsy from any accessible tumor at the recurrent or metastatic site available for central testing.
• 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 times the upper limit of normal (ULN)
• Serum ALT and AST = 2.5 x ULN for age,
• Adequate renal function
• 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 anticoagulant therapy 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.

2 - Specific inclusion criteria

2.1 - Inclusion criteria for cohort I1
• If the patient is pretreated with prior PD(L)1 compound blocker, criteria on protocol section 3.1.2.1 must be met.

2.2 - Inclusion criteria for cohort I2
• Pretreated patients with prior PD(L)1 compound blocker meeting all the criteria
on protocol section 3.1.2.2.

2.3 - Inclusion criteria for cohort B1 (p16 negative and EGFR amplification/mutation or PTEN high or HER2 amplification/mutation patients)
• Confirmed p16 negative immunohistochemistry (p16 positive is defined as H-score = 210) on the fresh biopsy
• Wild type for the known activating mutations in KRAS, NRAS and HRAS
• One of the specific criteria mentioned on protocol section 3.1.2.3 has to be fulfilled.

2.4 - Inclusion criteria for cohort B2 (p16 negative and cetuximab naïve patients)
• Confirmed p16 negative immunohistochemistry (p16 positive is defined as H-score = 210) on the fresh biopsy
• Cetuximab-naïve patient
• Wild type for the known

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 cardiovascular conditions within 6 months prior to registration
• Nasopharynx and sino-nasal tumor
• Surgery or investigational drugs or chemotherapy or other anticancer therapy within 3 weeks before cohort allocation
• Known untreated and uncontrolled brain metastases or leptomeningeal carcinomatosis
• Known diagnosis of immune deficiency or HIV
• Active Hepatitis B or C or pre-existing liver cirrhosis
• History of Extensive disseminated/bilateral or known presence of IDL, but not history of prior radiation pneumonitis
• Other uncontrolled active illnesses or nonmalignant systemic disease
• Any psychiatric, psychological, familial, sociological or geographical condition
• Any malignancy within the last 3 years prior to registration

2 - Specific exclusion criteria
2.1 - Exclusion criteria for cohort I1
• Systemic treatment with steroids or other immunosuppressive agents within 7d prior to cohort allocation
• History of allograft transplantation
• Active auto-immune disease/inflammatory disorders treated with systemic immunosuppressive drugs within the last 3 months or history of clinically severe auto-immune disease /inflammatory disorders
• Trt with cytokines or growth factors
• Known hypersensitivity to monalizumab or its excipients
• Receipt of live, attenuated vaccine within 30 days prior to registration

2.2 - Exclusion criteria for cohort I2
• The same listed for cohort I1, plus:
• More than 3 lines of systemic trt in the recurrent metastatic setting
• History of immune related disease without active immune related diseases in the last 5 years
• Immune related diseases
• Trt. with cytokines or growth factors
• Any chronic skin condition that requires systemic therapy
• Requiring therapeutic anticoagulation and irreversible platelet inhibitors
• Symptoms of spinal cord compression at randomization
• Known hypersensitivity to monalizumab or durvalumab or their excipients

2.3 - Exclusion criteria for cohort B1 and B2
• Patients with hereditary conditions of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
• Unresolved skin toxicities CTCAE v4.03 grade >1
• Trt. with any of the prohibited concomitant medications related to afatinib that cannot be stopped at the time of trial participation
• Significant or recent acute gastrointestinal disorders with diarrhea as major symptom
• Any of the following additional gastrointestinal disorders associated with high risk of perforation
• Known hypersensitivity to afatinib or the excipients of any of the trial drugs

2.4 - Exclusion criteria for cohort B3
• Food or drugs that are known to be CYP3A4 inhibitors or inducers related to palbociclib
• Drugs known to prolong the QT interval
• Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug
• Prior radiotherapy to 25% of bone marrow
• Inability to swallow and using a feeding tube
• Significant acute GI disorders with diarrhea as major symptom
• Any previous trt with another CDK4/6 inhibitor
• Known hypersensitivity to palbociclib and its excipients

2.5 - Exclusion criteria for cohort B4and B5
• Transfusion < 4 weeks prior to cohort allocation
• Colony-stimulating factors within 4 weeks prior cohort allocation
• Any known grade 3 or 4 anemia, neutropen

Study & Design

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