An Open Label, Phase 1B Safety Evaluation of Patritumab (U31287) in Combination With Cetuximab Plus Platinum Containing Therapy In Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Overview
- Phase
- Phase 1
- Intervention
- Cisplatin
- Conditions
- Squamous Cell Carcinoma of the Head and Neck
- Sponsor
- Daiichi Sankyo
- Enrollment
- 15
- Locations
- 2
- Primary Endpoint
- Percentage of participants experiencing dose-limiting toxicities (DLTs)
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The purpose of this study is to test a study drug called patritumab. Patritumab may work when combined with other medications that are approved in the UK for treating Squamous Cell Carcinoma of the Head and Neck (SCCHN), called cetuximab, cisplatin or carboplatin. It is hoped that patritumab may have some benefit in treating patients with cancer. This study will help identify how much patritumab can be given in combination with cetuximab, and cisplatin or carboplatin. This study will show how safe and how well tolerated patritumab is when these medications are given together.
Detailed Description
The trial will be performed in two "phases" (Periods): Period 1: Initial phase in which the recommended phase 2 dose (RP2D) is determined Period 2: Extension phase in which participants who are deriving benefit (stable disease or better) will have the opportunity to continue treatment at the discretion of the Investigator
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed recurrent disease or metastatic SCCHN originating from the oral cavity, oropharynx, hypopharynx, and larynx
- •Has documented disease recurrence following prior treatment
- •Has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Has adequate hematological function, per protocol
- •Has adequate renal function, per protocol
- •Has adequate hepatic function, per protocol
- •Has prothrombin time (PT) or partial thromboplastin time (PTT) within 1.5 x upper limit of normal (ULN)
- •Has a negative serum pregnancy test performed within 14 days prior to enrollment (where required by local regulations, test may be required within 72 hours prior to enrollment), if a woman of child-bearing potential
- •Agrees to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last study dose received, if of child-bearing potential
- •Is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Exclusion Criteria
- •Has left ventricular ejection fraction (LVEF) \< 50%
- •Has received prior epidermal growth factor receptor (EGFR) targeted regimen
- •Has received prior anti-HER2, anti-HER3, or anti-HER4 therapy
- •Has received prior treatment for recurrent/metastatic disease
- •Has 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 ≥ 5 years
- •Has known history of and active brain metastases
- •Has uncontrolled hypertension (systolic \> 160 mm Hg or diastolic \> 100 mm Hg)
- •Has clinically significant electrocardiogram (ECG) changes
- •Has had 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
- •Had platinum-containing drug therapy/chemotherapy with radiotherapy \< 6 months before study drug treatment
Arms & Interventions
All Participants - Period 1
All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin) in Period 1 - Initial phase of the trial.
Intervention: Cisplatin
All Participants - Period 1
All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin) in Period 1 - Initial phase of the trial.
Intervention: Patritumab
All Participants - Period 1
All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin) in Period 1 - Initial phase of the trial.
Intervention: Cetuximab
All Participants - Period 1
All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin) in Period 1 - Initial phase of the trial.
Intervention: Carboplatin
All Participants - Period 2
Participants deriving clinical benefit enter Period 2 - Extension phase, during which they continue to receive patritumab with cetuximab, but not platinum-based therapy.
Intervention: Patritumab
All Participants - Period 2
Participants deriving clinical benefit enter Period 2 - Extension phase, during which they continue to receive patritumab with cetuximab, but not platinum-based therapy.
Intervention: Cetuximab
Outcomes
Primary Outcomes
Percentage of participants experiencing dose-limiting toxicities (DLTs)
Time Frame: 6 months
DLTs are used to determine the maximum tolerated dose.
Secondary Outcomes
- Pharmacokinetic profile of serum cetuximab(6 months)
- Titer of HAHA formation (anti-patritumab antibodies)(6 months)
- Percentage of participants with human anti-human antibody (HAHA) formation (anti-patritumab antibodies)(6 months)
- Pharmacokinetic profile of serum patritumab(6 months)