Brief Title
Evaluation of GTPase Inhibition by Post-operative Intravenous Ketorolac in Ovarian Cancer Patients
Official Title
A Randomized Placebo-controlled Evaluation of GTPase Inhibition by Post-operative Intravenous Ketorolac in Ovarian Cancer Patients
Brief Summary
There is a move towards personalized medicine in cancer care, and significant effort is
underway to evaluate new targeted therapeutics for the treatment of ovarian cancer. One way
to identify potential new drug targets is by screening a drug library to determine whether
drugs in the library target key kinase or enzymatic sites in cellular signaling pathways.
Previous preclinical work and pilot studies demonstrated that ketorolac (a type of
non-steroidal anti-inflammatory drug) inhibits GTPase activity in ovarian cancer cells
retrieved from the post-operative peritoneal cavity.
The purpose of this study is to confirm that this inhibitory effect is ketorolac driven and
not a specific effect of the post-operative peritoneal compartment.
Detailed Description
Drug repurposing, screening a library of FDA approved agents, can identify agents that are
clinically available and for which pharmacology and pharmacokinetics are known and
preclinical data can be generated rapidly without the subsequent need for GMP (good
manufacturing practice) new drug production. Small GTPases, including members of the Rab, Ras
and Rho families, are attractive targets for the development of cancer therapeutics based on
their pivotal roles in protein trafficking, proliferation/survival and cytoskeletal
organization, respectively. Ketorolac tromethamine is a non-steroidal anti-inflammatory drug
that was identified in previous in-silico drug screens to be an inhibitor of GTPases. In a
previous phase 0 clinical study, ketorolac was administered intravenously to ovarian cancer
patients following optimal cytoreductive surgery. Ovarian cancer cells were obtained at the
time of surgery, prior to ketorolac administration, and at various times after ketorolac
dosing. Analysis of GTPase activity in these specimens showed a time-dependent inhibition of
Rac1 and Cdc42 GTPase activity. The purpose of this study is to confirm that the effect is
ketorolac driven and not a specific effect of the post-operative peritoneal compartment.
Study Type
Interventional
Primary Outcome
Ketorolac inhibition of GTPase activity
Secondary Outcome
Intraperitoneal and serum pharmacokinetics of ketorolac
Condition
Ovarian Cancer
Intervention
Ketorolac
Study Arms / Comparison Groups
Ketorolac
Description: Once deemed stable in the first 1-3 post-operative days, patients will be receive age-based ketorolac (30 mg <65, 15mg > 65) daily for three days
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
21
Start Date
October 29, 2015
Completion Date
October 8, 2025
Primary Completion Date
March 31, 2023
Eligibility Criteria
Inclusion Criteria:
- Patients must be suspected of having a diagnosis of ovarian, fallopian tube or primary
peritoneal cancer with a planned cytoreductive surgery.
- Borderline ovarian cancer with ascites is allowable.
- ECOG/Zubrod/SWOG Performance Status <2 (Karnofsky Performance Status > 70%)
- Female' age ≥18 years
- Ability to provide informed consent
- Baseline laboratory values (bone marrow, renal, hepatic):
- Adequate bone marrow function:
- Absolute neutrophil count >1000/µL
- Platelet count >100'000/µL
- Renal function:
- Serum creatinine < 1.5 x ULN
- Hepatic function:
- Bilirubin <1.5x normal
- Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase
[AST]) or serum glutamic-pyruvic transaminase (SGPT) (alanine
aminotransferase [ALT]) levels ≤ 2 x ULN
- No known bleeding disorders
- No known sensitivity or allergy to NSAIDs
- No active peptic ulcer disease
- No active bleeding
Secondary Eligibility
- Histologic diagnosis of epithelial ovarian, fallopian tube or primary peritoneal
cancer confirmed on frozen section diagnosis during debulking surgery
- Attempted maximal cytoreductive surgery. Patients will still be eligible whether
optimal or suboptimally debulked at the completion of the surgery.
- No active bleeding in the post-operative period
Exclusion Criteria:
- Non-epithelial ovarian cancer or metastatic cancer from another site to the ovaries
- Borderline ovarian cancer without ascites
- Uncontrolled or unstable medical conditions
- Off study use of ketorolac or other NSAIDs prior to study administration within the
perioperative window (7 days before surgery and up to the time of planned study
administration)
- Active bleeding or high risk of bleeding
- Active therapeutic anticoagulation
- Known hypersensitivity to NSAIDs
- Chronic or acute renal insufficiency as defined by a preoperative serum creatinine
greater than 1.5 mg/dL or creatinine clearance of < 40 ml/min
- Any co-morbid condition that' in the view of the attending physician' renders the
patient at high risk from ketorolac treatment complications
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Carolyn Y. Muller, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02470299
Organization ID
INST 1420
Responsible Party
Sponsor
Study Sponsor
New Mexico Cancer Care Alliance
Study Sponsor
Carolyn Y. Muller, MD, Principal Investigator, University of New Mexico Comprehensive Cancer Center
Verification Date
October 2022