Sym004 in head and neck cancer patients failing anti-EGFR based therapy
- Conditions
- Recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN)MedDRA version: 14.1Level: PTClassification code 10067821Term: Head and neck cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-000902-24-DE
- Lead Sponsor
- Symphogen A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 25
1. Histologically confirmed diagnosis initially or at relapse of SCCHN of the oral cavity, oropharynx, hypopharynx or larynx
2. Recurrent and/or metastatic SCCHN not amenable to curative treatment with surgery and/or (chemo)radiation
3. Previous treatment with a marketed anti-EGFR mAb in the palliative setting either as monotherapy or in combination with chemotherapy or radiotherapy and showing:
a. Documented clinical benefit or response for at least 8 weeks (PR, CR or SD verified by CT scan or MRI according to RECIST) on the anti-EGFR mAb-based therapy and
b. Documented disease progression (PD verified by CT scan or MRI according to RECIST) during or within 12 weeks following the last administration of anti-EGFR mAb
4. Accessible tumor for biopsy and patient acceptance of repeat tumor biopsies
5. At least one measurable lesion according to RECIST (1.1) at screening*
6. ECOG performance status 0-1
7. Normal organ or bone marrow function as defined below:
a. ANC > 1.5 x109/L (1,500/mm3)
b. Hemoglobin = 9 g/dl
c. Platelet count = 75 x109/L (75,000/mm3)
d. Bilirubin < 1.5 x upper normal limit
e. Alkaline Phospatase = 2.5 x upper normal limit (unless known bone metastases)
f. AST(SGOT)/ALT(SGPT) = 2.5 x upper normal limit (unless known liver metastases)
g. Serum creatinine =1.5 x upper normal limit or creatinine clearance > 50 ml/min calculated according to Cockroft-Gault
h. S-Na, S-K, S-Mg and S-Ca CTCAE < grade 3 for both low and high values
8. Age =18 years
9. Following receipt of verbal and written information about the trial, the patient must provide signed informed consent before any trial related activity is carried out
* Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 13
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12
1. More than 2 lines of prior chemotherapy in the palliative setting
2. Expected survival <12 weeks
3. Patients with known brain metastases
4. Chemotherapy or radiation therapy within 21 days prior to Visit 2 at the exception of palliative radiotherapy for bleeding or pain, which is allowed anytime, if not given on target lesions
5. Anti-EGFR mAbs within 14 days prior to Visit 2
6. Patients with known previous grade > 3 infusion related reactions with chimeric monoclonal antibodies
7. History of other malignancy within 5 years prior to Visit 2, with the exception of basal cell carcinoma of the skin and carcinoma in situ of the cervix or urinary bladder
8. Severe infection requiring iv treatment
9. Any other concurrent uncontrolled disease or medical conditions that are deemed to interfere with the conduct of the trial as judged by the investigator
10. Major surgery within 4 weeks prior to Visit 2 and patients must have recovered from effects of major surgery
11. Known HIV positive
12. Known active hepatitis B or C
13. Patients with known allergy to the components in the study drug
14. Clinically significant and uncontrolled cardiac disease including unstable angina, acute myocardial infarction within six months prior to Visit 2, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities and controlled and well treated chronic atrial fibrillation
15. Current participation in any other interventional clinical trial
16. Patients known or suspected of not being able to comply with this trial protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
17. Male patients not willing to use adequate contraception or female of childbearing potential not willing to use an effective form of contraception such as hormonal birth control, intrauterine device or double barrier method during treatment with Sym004 and at least 3 months thereafter
18. Breast feeding women or women with a positive pregnancy test at Visit 1
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): Rate of Progression Free Survival (PFS) at 24 weeks;Timepoint(s) of evaluation of this end point: At 24 weeks;Main Objective: To assess the efficacy of Sym004 in patients with recurrent and/or metastatic SCCHN who have disease progression during or within 12 weeks after treatment with an anti-EGFR mAb-containing regimen;Secondary Objective: • To assess the safety profile of Sym004<br>• To assess the biological activity in tumor and skin biopsies<br>• To determine overall survival (OS)<br>• To evaluate potential biomarkers<br>• To determine the pharmacokinetic profile of Sym004<br>
- Secondary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: Clinical assessment takes place on an ongoing basis during the study;Secondary end point(s): • Adverse events<br>• Objective tumor response (according to RECIST (1.1))<br>• Time to progression (TTP)<br>• Overall survival (OS)<br>• Skin rash (CTCAE grading (v. 4.02), duration)<br>• Biomarkers (e.g. Circulating Tumor Cells, HPV, mutation of EGFR-vIII, KRAS, HRAS, NRAS, BRAF, PIK3CA, PTEN, Her2, Her3, c-Met)<br>• Pharmacokinetic profile (AUC, CL, Cmax, Cmin, T1/2)<br>• Host immune response: Antidrug antibody (ADA)<br>