A Study of Prexasertib (LY2606368) With Chemotherapy and Radiation in Participants With Head and Neck Cancer

Study Overview
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Brief Summary
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The main purpose of this study is to investigate the safety of prexasertib in combination with other anti-cancer drugs (cisplatin or cetuximab) and radiation therapy in participants with locally advanced head and neck cancer. The study has two parts (A and B). Participants will only enroll in one part.

Detailed Description
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The primary purpose of Parts A and B of this study is to determine a recommended dose level of prexasertib (an inhibitor of checkpoint kinase 1[Chk-1]) in combination with cisplatin and radiation therapy (Part A) or cetuximab and radiation therapy (Part B) in participants with locally advanced head and neck cancer.

Official Title
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A Phase 1b Trial of LY2606368 in Combination With Chemoradiation in Patients With Locally Advanced Head and Neck Squamous Cell Cancer

Conditions
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Head and Neck Neoplasms

Intervention / Treatment
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* Drug: Prexasertib
* Drug: Cisplatin
* Drug: Cetuximab
* Radiation: Intensity Modulated Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be able to comply with the treatment plan and follow-up schedule Must have diagnosis of head and neck squamous cell carcinoma of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls), hypopharynx, or larynx Have adequate organ function If participant is of reproductive potential, must agree to use medically approved contraceptive precautions during the study and for six months following the last dose of study drug If the participant is a female of childbearing potential, must have had a negative serum or urine pregnancy test within 14 days of the first dose of study drug and must not be breast feeding Exclusion Criteria: Must not have taken an unapproved drug as treatment for any indication within the last 28 days prior to starting study treatment Must not have received any of the following prior therapies or treatments: systemic therapy for the study cancer, radiation therapy to the head and neck region, or curative-intent surgery in the head and neck region Have evidence of a distant metastatic disease Must not have an active symptomatic fungal, bacterial or viral infection, including human immunodeficiency virus (HIV) or Hepatitis A, B, or C Must not have a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months Must not have a family history of long corrected QT interval (QTc) syndrome Must not have known allergic reaction against any of the components of the study treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prexasertib + Cisplatin + Radiation Therapy (Part A)<br>Prexasertib administered intravenously (IV) every 14 days over an approximately 49-day treatment period. Cisplatin administered IV every 7 days over an approximately 49-day treatment period. Intensity modulated radiation therapy administered 5 days per week over an approximately 49-day treatment period. Participants may remain on treatment until completion of the treatment period. | Drug: Prexasertib<br>* Administered IV<br>* Other names: LY2606368;Drug: Cisplatin<br>* Administered IV<br>Radiation: Intensity Modulated Radiation Therapy<br> <br> |
| Experimental: Prexasertib + Cetuximab + Radiation Therapy (Part B)<br>Prexasertib administered IV every 14 days over an approximately 56-day treatment period. Cetuximab administered IV every 7 days over an approximately 56-day treatment period. Intensity modulated radiation therapy administered 5 days per week over an approximately 56-day treatment period (starting at Week 2). Participants may remain on treatment until completion of the treatment period. | Drug: Prexasertib<br>* Administered IV<br>* Other names: LY2606368;Drug: Cetuximab<br>* Administered IV<br>* Other names: LY2939777;Radiation: Intensity Modulated Radiation Therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Maximum Tolerated Dose of Prexasertib in Combination with Cisplatin and Radiation Therapy |  | First Dose through Last Dose (Estimated up to 7 Weeks) | 
| Part B: Maximum Tolerated Dose of Prexasertib in Combination with Cetuximab and Radiation Therapy |  | First Dose through Last Dose (Estimated up to 8 Weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Concentration of Prexasertib, Cisplatin and Cetuximab |  | First Dose through Last Dose (Estimated up to 8 Weeks) | 
| PK: Area Under the Concentration Curve (AUC) of Prexasertib |  | First Dose through Last Dose (Estimated up to 8 Weeks) | 
| Locoregional Control Rate |  | Baseline through One Year (Estimated as up to 52 Weeks) or Death from Any Cause | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer