Randomized, placebo-controlled, double-blind phase 2 study of patritumab (U3-1287) in combination withcetuximab plus platinum-based therapy in first line setting in subjects with recurrent or metastatic squamous cell carcinoma of the head and neck
- Conditions
- Recurrent or metastatic squamous cell carcinoma of the headand neck
- Registration Number
- DRKS00009967
- Lead Sponsor
- Daiichi Sankyo Pharma Development
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 105
1. Adult subjects =18 years old
2. Histologically confirmed recurrent disease or metastatic SCCHN tumor and/or from its lymph nodal metastases originating from the oral cavity, oropharynx, hypopharynx, and larynx
3. Heregulin expression level is required
- Samples must be taken from subjects who have recurrent or metastatic disease (rec/met). These samples can be from either rec/met archived or fresh biopsy samples (either primary tumor or metastases)
- No cancer treatment between time of biopsy and submission of sample
- Surgical or core needle biopsy is acceptable
- Fine-needle aspiration or cytology is not acceptable for biopsies
4. HPV status or p16 (surrogate for HPV) is required. These results must come from tumor tissue. These results may be obtained from either a local lab or samples sent to the central lab. HPV or p16 status can be from any tumor biopsy material from initial diagnosis
5. Measurable disease per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
7. Hematological function, as follows:
- Absolute neutrophil count (ANC) = 1.5 x 109/L
- Platelet count = 100 x 109/L
- Hemoglobin = 10 g/dL
8. Renal function, as follows:
- Estimated serum creatinine clearance (mL/min) as an estimate of GFR = 60 mL/min for cisplatin and = 30 mL/min for carboplatin (Note: GFR will not be directly measured in this protocol)
9. Hepatic function, as follows:
- Aspartate aminotransferase (AST) = 2.5 x upper limit of normal (ULN) (if liver metastases are present, < 5 x ULN)
- Alanine aminotransferase (ALT) = 2.5 x ULN (if liver metastases are present, < 5 x ULN)
- Alkaline phosphatase = 2.0 x ULN (if bone or liver metastases are present, < 5 x ULN)
- Bilirubin = 1.5 x ULN
10. Prothrombin time or partial thromboplastin time = 1.5 x ULN
11. Women of childbearing potential must have a negative serum pregnancy test performed within 14 days prior to enrollment (where demanded by local regulations, test may be required within 72 hours prior to enrollment)
12. Adult subjects of child-bearing potential must agree to use double-barrier contraceptive measures. Two of the following precautions must be used: bilateral vasectomy, bilateral tubal ligation, intrauterine device (IUD), combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine hormone-releasing system (IUS), condom with spermicide, abstinence. These contraception measures must be used for the entire duration of the study and for 6 months after the last study dose is received-
13. Subjects must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
14. Provided written informed consent(s)
1. Left ventricular ejection fraction (LVEF) <50%
2. Prior EGFR targeted regimen
3. No HRG expression result
4. No HPV or p16 status
5. Prior anti-HER3 therapy
6. Prior chemotherapy for recurrent/metastatic disease
7. Anti-cancer therapy between biopsy and submission of sample
8. Presence of squamous cell tumors of the nasopharynx
9. History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for = 2 years
10. Known history of brain metastases or active brain metastases
11. Uncontrolled hypertension (systolic > 160 mm Hg or diastolic > 100 mm Hg)
12. Clinically significant electrocardiograph (ECG) findings
13. Myocardial infarction within 1 year before enrollment, symptomatic congestive heart failure (New York Heart Association >Class II), unstable angina, or unstable cardiac arrhythmia requiring medication
14. Platinum-containing drug therapy with radiotherapy less than 6 months before study drug treatment
15. Therapeutic or palliative radiation therapy or major surgery within 4 weeks before study drug treatment. Radiation treatment to all sites of measureable disease unless progression is documented after radiation
16. Participated in clinical drug trials within 4 weeks before study drug treatment.
Current participation in other investigational procedures
17. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known HIV infection, or active hepatitis B or C infection or undergoing medical treatment for infection
18. Uncontrolled type 1 or 2 diabetes mellitus
19. Known hypersensitivity or allergic reaction against any of the components of the trial treatment
20. Pregnant, breastfeeding, or unwilling/unable to use acceptable contraception
21. Residual toxicities = Grade 1 from previous therapies that the Investigator determines would exclude participation
22. Psychological, social, familial, or geographical factors that would interfere with study participation or follow-up
23. Committed to an institution by virtue of an order issued either by judicial or administrative authorities
24. Employee or immediate relative of an employee of the sponsor, CRO, the study center, or their affiliates or partners
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression free survival in the Heregulin high expression population from subjects treated with patritumab + cetuximab + platinum-based therapy compared to placebo + cetuximab + platinum-based therapy
- Secondary Outcome Measures
Name Time Method Overall survival; Objective response rate; PK parameters of serum cetuximab and platinum concentrations when cetuximab and cisplatin or carboplatin are coadministered with patritumab in a subgroup (n=30) of subjects; Population PK of patritumab; Incidence of HAHA formation (anti-patritumab antibodies); Safety and tolerability of the combination of patritumab + cetuximab + platinum-based therapy in first-line treatment of subjects with Squamous cell carcinoma of the head and neck