Clinical Trial: Cisplatin With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Randomized Phase II Trial of Cisplatin With or Without Wee1 Kinase Inhibitor AZD1775 (MK-1775) for First-line Treatment of Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck (RM-SCCHN

Brief Summary: This randomized phase II trial studies how well cisplatin with or without WEE1 inhibitor MK-1775 works in treating patients with head and neck cancer that has come back or has spread to other parts of the body. Drugs used in chemotherapy, such as cisplatin, may prevent tumor cells from multiplying by damaging their deoxyribonucleic acid (DNA), which in turn stops the tumor from growing. WEE1 inhibitor MK-1775 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cisplatin is more effective with or without WEE1 inhibitor MK-1775 in treating patients with head and neck cancer.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To compare the overall response rate assess the efficacy of MK-1775 (WEE1 inhibitor MK-1775) in combination with cisplatin to cisplatin alone in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) as per overall response rate (using Response Evaluation Criteria in Solid Tumors [RECIST] criteria version [v]1.1).

SECONDARY OBJECTIVES:

I. Assess secondary measures of efficacy (progression free survival at 6 months and 12 months, overall survival rate at 12 months).

II. Assess measures of efficacy by tumor protein (p)53 status. III. Evaluate safety and tolerability. IV. Explore predictive and pharmacodynamic biomarkers.

OUTLINE:

SAFETY RUN-IN: Patients receive WEE1 inhibitor MK-1775 orally (PO) twice daily (BID) for 5 doses beginning on day 1 and cisplatin intravenously (IV) over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.

ARM II: Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are foll
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Overall Response Rate (Complete Plus Partial Response) Using RECIST Criteria v1.1 [ Time Frame: Up to 1 year ]

Per Response Evaluation Criteria in solid Tumors (RECIST1.1) Target lesions are assessed as Complete Response(CR), Disappearance of all target lesions; Partial Response (PR),30% decrease in the sum of the diameters of target lesions; Progressive Disease (PD), At least a 20% increase (minimum 5 mm) from smallest sum (nadir); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Nontarget lesions are assessed as Complete Response (CR), Disappearance of all non-target lesions; Non-CR/Non-PD, Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits; Progressive Disease (PD),Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions; Overall Response(OR); PR=CR+non-CR/non-PD,SD=SD+non-PD; PD=PD+presence of any non-target lesions


Original Primary Outcome: Overall Response Rate (Complete Plus Partial Response) Using RECIST Criteria v1.1 [ Time Frame: Up to 1 year ]

All analyses will be performed with an intention to treat. The one-sided Z test will be used to compare the response rate between the treatment and control groups.


Current Secondary Outcome:

  • Incidence of Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [ Time Frame: Up to 1 year ]
    Gr 3, Gr 4 and Gr 5 AEs at least possibly related to study drug
  • Levels of Pharmacodynamic Biomarkers [ Time Frame: Pre-dose, at 4-8 hours on day 3 or 20-24 hours on day 4 ]
    Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Descriptive statistics and plotting of data will be used to better understand potential relationships.
  • Levels of Predictive Biomarkers [ Time Frame: Up to day 4 of course 1 ]
    Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Descriptive statistics and plotting of data will be used to better understand potential relationships.
  • Overall Survival [ Time Frame: 12 months ]
    Estimated in each group by the Kaplan Meier method and differences between groups will be calculated by the log rank test. Hazard ratios for each group will be estimated using the Cox Regression model.
  • Progression Free Survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed at 6 months ]
    Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression (20% increase in the sum of the longest diameter of target lesions or a measurable increase in a non-target lesion, or the appearance of new lesions) or death, whichever occurs first.
  • Progression Free Survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed at 12 months ]
    Estimated in each group by the Kaplan Meier method and differences between groups will be calculated by the log rank test. Hazard ratios for each group will be estimated using the Cox Regression model.


Original Secondary Outcome:

  • Progression Free Survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed at 6 months ]
    Estimated in each group by the Kaplan Meier method and differences between groups will be calculated by the log rank test. Hazard ratios for each group will be estimated using the Cox Regression model.
  • Progression Free Survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed at 12 months ]
    Estimated in each group by the Kaplan Meier method and differences between groups will be calculated by the log rank test. Hazard ratios for each group will be estimated using the Cox Regression model.
  • Overall Survival [ Time Frame: 12 months ]
    Estimated in each group by the Kaplan Meier method and differences between groups will be calculated by the log rank test. Hazard ratios for each group will be estimated using the Cox Regression model.
  • Incidence of Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [ Time Frame: Up to 1 year ]
    Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.
  • Levels of Predictive Biomarkers [ Time Frame: Up to day 4 of course 1 ]
    Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Descriptive statistics and plotting of data will be used to better understand potential relationships.
  • Levels of Pharmacodynamic Biomarkers [ Time Frame: Pre-dose, 1 hour, 2 hour, 4 hour, and 6 hour on days 1 and 2 of course 1 ]
    Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Descriptive statistics and plotting of data will be used to better understand potential relationships.


Information By: National Cancer Institute (NCI)

Dates:
Date Received: July 18, 2014
Date Started: March 2014
Date Completion:
Last Updated: March 22, 2017
Last Verified: March 2017