| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Squamous Cell Carcinoma of the Head and Neck |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10060121 |
| E.1.2 | Term | Squamous cell carcinoma of head and neck |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
• To evaluate progression-free survival (PFS) in the heregulin (HRG) high expression population from subjects treated with patritumab + cetuximab + platinum-based therapy compared to placebo + cetuximab + platinum-based therapy.
|
|
| E.2.2 | Secondary objectives of the trial |
• Evaluate overall survival (OS)
• Evaluate overall response rate (ORR)
• Refine the cutoff between heregulin high and low expression based on clinical data from this study
• Assess the population PK of patritumab in subjects with SCCHN
• Assess the PK parameters of serum cetuximab and platinum concentrations when cetuximab and cisplatin or carboplatin (platinum-based therapy) are coadministered with patritumab in a sub group (n = 30) of subjects
• Evaluate the incidence of human antihuman antibody (HAHA) formation (anti-patritumab antibodies)
• Evaluate the safety and tolerability of the combination of patritumab + cetuximab + platinum-based therapy in first-line treatment of subjects with SCCHN |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
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. These samples can be from either rec/met archived or fresh biopsy samples
- 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. Human papilloma virus (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 performance status 0 or 1
7. Hematological function, as follows:
- Absolute neutrophil count ≥ 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) or glomerular filtration rate (GFR) ≥ 60 mL/min for cisplatin and ≥ 30 mL/min for carboplatin
9. Hepatic function, as follows:
- Aspartate aminotransferase ≤ 2.5 x upper limit of normal (ULN) (if liver metastases are present, < 5 x ULN)
- Alanine aminotransferase ≤ 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 schedule visits, treatment plan, laboratory tests, and other study procedures
14. Provided written informed consent(s) |
|
| E.4 | Principal exclusion criteria |
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
25. Receiving yellow fever vaccine or live attenuated vaccines (for subjects
receiving carboplatin)
26. Presence of hemorrhagic tumors (for subjects receiving carboplatin)
27. Prophylactic use of phenytoin or fosphenytoin (for subjects receiving
cisplatin or carboplatin) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| 1) Progression free survival (PFS) in the HRG high expression population from subjects treated with patritumab + cetuximab + platinum-based therapy compared to placebo + cetuximab + platinum-based therapy |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) The time from the date of randomization to the earlier of the dates of the first objective
documentation of radiographic disease progression (per RECIST v1.1 as assessed by investigator) or death due to any cause. |
|
| E.5.2 | Secondary end point(s) |
2) Overall survival (OS)
3) Objective response rate (ORR)
4) 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
5) Population PK of patritumab
6) Incidence of HAHA formation (anti-patritumab antibodies)
7) Safety and tolerability of the combination of patritumab + cetuximab + platinum-based therapy in first-line treatment of subjects with SCCHN |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
2) Date of randomization to death due to any cause
2) Subjects alive at time of data cut off for OS analysis will be censored at the last contact date at which subject is known to be alive
3) Proportion of subjects with the best ORR of CR or PR regardless of whether it is confirmed or unconfirmed
4) Refer to schedule of events
5) Refer to schedule of events
6) Refer to schedule of events
7) Refer to schedule of events |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Until all subjects have died or a minimum of 13 months after the last subject is randomized whichever comes first |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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