Evaluation of GTPase Inhibition by Post-operative Intravenous Ketorolac in Ovarian Cancer Patients

NCT02470299 | Completed DMC

• 1 other identifier: INST 1420
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer

Keywords

ketorolac; GTPase; cancer; peritoneal; fallopian; ovarian

Outcome Measures

Primary Outcomes (1)

• Ketorolac inhibition of GTPase activity

  Ovarian cancer cells retrieved from the post-debulked peritoneal cavity after three intravenous dosings of ketorolac will be evaluated for GTPase activity using cell-based laboratory assays

  Within 4 weeks of peritoneal cell collection

Secondary Outcomes (3)

• Intraperitoneal and serum pharmacokinetics of ketorolac

  Within 4 weeks of peritoneal and blood specimen collection

• Time to CA-125 normalization

  Up to 6 months following first ketorolac treatment

• Toxicity assessment

  Up to 30 days following first ketorolac treatment

Other Outcomes (2)

• Overall survival (Exploratory objective)

  Up to 5 years following first ketorolac treatment

• Progression free survival (Exploratory objective)

  Up to 18 months following first ketorolac treatment

Study Arms (2)

Ketorolac

EXPERIMENTAL

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

Drug: Ketorolac

Placebo

PLACEBO COMPARATOR

Once deemed stable in the first 1-3 post-operative days, patients will be receive placebo daily for three days

Other: Placebo

Interventions

Ketorolac DRUG

Ketorolac tromethine 15 mg or 30 mg doses will be administered via intravenous (IV) push undiluted over 15 - 30 seconds Ketorolac will be dosed according to FDA approved recommendations. For planned three daily dose (IV) based on clinical scenario: * Patients \< 65 years of age: Daily dose of 30 mg for three doses. * Patients ≥ 65 years of age, renally impaired and/or less than 50 kg (110 lbs) of body weight: Daily dose of 15 mg for three doses Blood and peritoneal fluid will be drawn prior to each dose (time 0, 24, 48, 72 hr) as well as at 6 hr after the first dose

Also known as: Toradol

Ketorolac

Placebo OTHER

Equivalent volume of normal saline will be set in the syringe for each daily dose registered for the patient in a blinded fashion. The volume will be determined by the dose calculation as follows: For planned three daily dose (IV) based on clinical scenario: * Patients \< 65 years of age: Daily dose of 30 mg for three doses. * Patients ≥ 65 years of age, renally impaired and/or less than 50 kg (110 lbs) of body weight: Daily dose of 15 mg for three doses. Blood and peritoneal fluid will be drawn prior to each dose (time 0, 24, 48, 72 hr) as well as at 6 hr after the first dose

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• New Mexico Cancer Research Alliance: lead

Study Sites (1)

Universtiy of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87131-0001, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms; Neoplasms

Interventions

Ketorolac; Ketorolac Tromethamine

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Carolyn Y. Muller, MD

  University of New Mexico Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2015
• First Posted: June 12, 2015
• Study Start: October 29, 2015
• Primary Completion: October 8, 2018
• Study Completion: January 25, 2024
• Last Updated: May 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)