Clinical trial NCT02555644: A Study of Prexasertib (LY2606368) With Chemotherapy and Radiation in Participants With Head and Neck Cancer
Official title: A Phase 1b Trial of LY2606368 in Combination With Chemoradiation in Patients With Locally Advanced Head and Neck Squamous Cell Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Head and Neck Neoplasms
Keywords: cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2015-09-21
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Part A: Maximum Tolerated Dose of Prexasertib in Combination with Cisplatin and Radiation Therapy
timeFrame: First Dose through Last Dose (Estimated up to 7 Weeks)
measure: Part B: Maximum Tolerated Dose of Prexasertib in Combination with Cetuximab and Radiation Therapy
timeFrame: First Dose through Last Dose (Estimated up to 8 Weeks)
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum Concentration of Prexasertib, Cisplatin and Cetuximab
timeFrame: First Dose through Last Dose (Estimated up to 8 Weeks)
measure: PK: Area Under the Concentration Curve (AUC) of Prexasertib
timeFrame: First Dose through Last Dose (Estimated up to 8 Weeks)
measure: Locoregional Control Rate
timeFrame: Baseline through One Year (Estimated as up to 52 Weeks) or Death from Any Cause
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Medical Center
state: Alabama
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Lyon
country: France
facility: Centre Leon Berard
city: Villejuif Cedex
country: France
facility: Gustave Roussy
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Zeng L, Nikolaev A, Xing C, Della Manna DL, Yang ES. CHK1/2 Inhibitor Prexasertib Suppresses NOTCH Signaling and Enhances Cytotoxicity of Cisplatin and Radiation in Head and Neck Squamous Cell Carcinoma. Mol Cancer Ther. 2020 Jun;19(6):1279-1288. doi: 10.1158/1535-7163.MCT-19-0946. Epub 2020 May 5.
citation: Zeng L, Beggs RR, Cooper TS, Weaver AN, Yang ES. Combining Chk1/2 Inhibition with Cetuximab and Radiation Enhances In Vitro and In Vivo Cytotoxicity in Head and Neck Squamous Cell Carcinoma. Mol Cancer Ther. 2017 Apr;16(4):591-600. doi: 10.1158/1535-7163.MCT-16-0352. Epub 2017 Jan 30.