Clinical Trial: Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Randomized Placebo-Controlled Phase II Trial Comparing Gemcitabine Monotherapy to Gemcitabine in Combination With AZD 1775 (MK 1775) in Women With Recurrent, Platinum Resistant Epithelial Ovarian, P

Brief Summary: This randomized phase II clinical trial studies how well gemcitabine hydrochloride and WEE1 inhibitor MK-1775 work compared to gemcitabine hydrochloride alone in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of time. Gemcitabine hydrochloride may prevent tumor cells from multiplying by damaging their deoxyribonucleic acid (DNA, molecules that contain instructions for the proper development and functioning of cells), which in turn stops the tumor from growing. The protein WEE1 may help to repair the damaged tumor cells, so the tumor continues to grow. WEE1 inhibitor MK-1775 may block the WEE1 protein activity and may increase the effectiveness of gemcitabine hydrochloride by preventing the WEE1 protein from repairing damaged tumor cells without causing harm to normal cells. It is not yet known whether gemcitabine hydrochloride with or without WEE1 inhibitor MK-1775 may be an effective treatment for recurrent ovarian, primary peritoneal, or fallopian tube cancer.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate the progression free survival (PFS) of subjects with recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer receiving gemcitabine (gemcitabine hydrochloride) in combination with AZD 1775 (MK-1775 [WEE1 inhibitor MK-1775]) compared to subjects receiving gemcitabine in combination with placebo.

SECONDARY OBJECTIVES:

I. To evaluate the objective response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of patients receiving gemcitabine combined with AZD 1775 (MK-1775) compared to patients receiving gemcitabine in combination with placebo.

II. To evaluate the Gynecologic Cancer Intergroup (GCIG) cancer antigen (CA)125 response rate of patients receiving gemcitabine combined with AZD 1775 (MK-1775) compared to patients receiving gemcitabine in combination with placebo.

III. To evaluate the overall survival of patients (max 1-year [yr] follow-up) receiving gemcitabine combined with AZD 1775 (MK-1775) compared to patients receiving gemcitabine in combination with placebo.

IV. To evaluate the safety and tolerability of the combination of gemcitabine combined with AZD 1775 (MK-1775) in patients with recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer.

V. To evaluate tumor protein p53 (TP53) mutations (presence of mutation and type of mutation) as potential predictive factors of benefit (defined as response or progression-free survival [PFS] prolongation) to AZD 1775 (MK-1775) and gemcitabine treatment.

VI. To evaluate p53 protein expr
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Progression free survival [ Time Frame: Time from start of treatment to time to progression or death, whichever occurs first, assessed up to 1 year ]

Progression free survival will be evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • CA125 response rate [ Time Frame: Up to 1 year ]
    The Gynecologic Cancer InterGroup CA125 response rate will be assessed.
  • Incidence of grade 3 or 4 serious adverse events, graded according to 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.
  • Objective response [ Time Frame: Up to 1 year ]
    Objective response will be evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1.
  • Overall survival [ Time Frame: Up to 1 year ]
    Survival estimates will be computed using the Kaplan-Meier method.
  • p53 protein expression [ Time Frame: Baseline ]
    Expression of p53 protein in archival tumor tissue will be measured by immunohistochemistry.
  • TP53 mutations [ Time Frame: Baseline ]
    Presence and type of TP53 mutations will be assessed by Sanger sequencing.


Original Secondary Outcome:

  • Objective response by RECIST version 1.1 [ Time Frame: Up to 1 year ]
  • GCIG CA125 response rate [ Time Frame: Up to 1 year ]
  • Overall survival [ Time Frame: Up to 1 year ]
    Survival estimates will be computed using the Kaplan-Meier method.
  • Incidence of grade 3 or 4 serious adverse events graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 1 year ]
  • TP53 mutations (presence and type of mutation) by Sanger sequencing [ Time Frame: Baseline ]
  • p53 expression in archival tumor tissue by immunohistochemistry (IHC) [ Time Frame: Baseline ]


Information By: National Cancer Institute (NCI)

Dates:
Date Received: March 28, 2014
Date Started: July 2014
Date Completion:
Last Updated: May 26, 2017
Last Verified: May 2017