Adavosertib Plus Chemotherapy in Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
NCT ID: NCT02272790
Last Updated: 2023-10-03
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
95 participants
INTERVENTIONAL
2015-01-30
2023-03-08
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
A Study of Adavosertib (MK-1775) in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone for Participants With Platinum-Sensitive Ovarian Tumors With the P53 Gene Mutation (MK-1775-004)
NCT01357161
AZD0530 Phase II Study in Patients With Advanced Ovarian Cancer
NCT00610714
A Phase IIclinical Trial of Carboplatin and Paclitaxel or Carboplatin and Gemcitabine in Platinum-sensitive, Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
NCT01570582
Erlotinib Plus Carboplatin and Paclitaxel in Ovarian Carcinoma
NCT00059787
Combination Chemotherapy in Treating Patients With Ovarian Epithelial, Fallopian Tube, or Peritoneal Cancer
NCT00031954
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
The adavosertib plus paclitaxel arm (Arm B) will enrol approximately 30 additional patients at selected sites as part of a further efficacy evaluation based on emerging data that suggests clinical activity.
In addition, the adavosertib plus carboplatin arm (Arm C) will enrol approximately 23 patients overall at selected sites as part of a further efficacy evaluation based on emerging data that suggests clinical activity.
To further optimise the dosing schedule of adavosertib in Arm C, a safety expansion arm (referred to as Arm C2) of approximately 12 additional patients will be enrolled at selected sites to explore emerging pre-clinical and clinical data that suggest that prolonged adavosertib exposure may increase the clinical activity.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm A (adavosertib + gemcitabine)
Adavosertib (175 mg PO) will be taken on Days 1-2, 8-9, and 15-16. Gemcitabine 800 mg/m² will be administered IV on days 1, 8, and 15 of each 28 day cycle.
Adavosertib
Adavosertib will be taken as oral capsules with water, approx. 2 hours before or 2 hours after food.
Gemcitabine
Gemcitabine 800 mg/m² will be administered IV on Days 1, 8, and 15 of each 28-Day cycle.
Arm B (adavosertib + paclitaxel)
Five doses of adavosertib (225 mg PO BID) will be taken in approximate 12 hour intervals over 2.5 days weekly (Days 1-3, 8-10, and 15-17). Weekly paclitaxel 80 mg/m² IV will be administered according to institutional standards on Day 1, 8, and 15 of each 28 day cycle.
Adavosertib
Adavosertib will be taken as oral capsules with water, approx. 2 hours before or 2 hours after food.
Paclitaxel
Paclitaxel will be administered as a 1-hour IV infusion (± 10 minutes) at a dose of 80 mg/m2 according to institutional standards on Days 1, 8, and 15 of each 28 Day cycle.
Patients should be pre-medicated with corticosteroids, diphenhydramine and/or H2 antagonists according to institutional standards.
Arm C/C2 (adavosertib + carboplatin)
Arm C: Five doses of adavosertib (225 mg PO BID) will be taken in approximate 12 hour intervals over 2.5 days (Days 1-3). Carboplatin AUC 5 IV will be administered according to institutional standards on Day 1 of each 21-Day cycle.
Arm C2: Five doses of adavosertib (225 mg PO BID) 2.5 days per dosing week (QW), on Weeks 1 (D1-3), 2 (D8-10) and 3 (D15-17), or on Weeks 1 (D1-3) and 2 (D8-10) ( 2 weeks on followed by 1 week off.) Carboplatin AUC 5 IV will be administered according to institutional standards on Day 1 of each 21 day cycle.
Adavosertib
Adavosertib will be taken as oral capsules with water, approx. 2 hours before or 2 hours after food.
Carboplatin
Carboplatin, at a dose calculated to produce an AUC of 5 will be administered by intravenous infusion according to institutional standards on Day 1 of each 21 Day cycle. The carboplatin dose will be calculated using the Calvert Formula based on the patient's glomerular filtration rate (GFR) which is estimated by using the creatinine clearance.
Arm D (adavosertib + PLD)
Five doses of adavosertib (175 mg or 225 mg) will be taken in approximate 12 hour intervals over 2.5 days (Days 1, 2, and 3) of each 28-day cycle. PLD will administered IV on Day 1 of each cycle.
Adavosertib
Adavosertib will be taken as oral capsules with water, approx. 2 hours before or 2 hours after food.
PLD
PLD (pegylated liposomal doxorubicin) 40 mg/m² IV will be given on Day 1 of each 28-Day cycle.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Adavosertib
Adavosertib will be taken as oral capsules with water, approx. 2 hours before or 2 hours after food.
Paclitaxel
Paclitaxel will be administered as a 1-hour IV infusion (± 10 minutes) at a dose of 80 mg/m2 according to institutional standards on Days 1, 8, and 15 of each 28 Day cycle.
Patients should be pre-medicated with corticosteroids, diphenhydramine and/or H2 antagonists according to institutional standards.
Carboplatin
Carboplatin, at a dose calculated to produce an AUC of 5 will be administered by intravenous infusion according to institutional standards on Day 1 of each 21 Day cycle. The carboplatin dose will be calculated using the Calvert Formula based on the patient's glomerular filtration rate (GFR) which is estimated by using the creatinine clearance.
Gemcitabine
Gemcitabine 800 mg/m² will be administered IV on Days 1, 8, and 15 of each 28-Day cycle.
PLD
PLD (pegylated liposomal doxorubicin) 40 mg/m² IV will be given on Day 1 of each 28-Day cycle.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Histologic or cytologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer.
* Progressed within 6 months of completing at least 4 cycles of a first-line platinum-containing regimen for Stage III/IV disease. Patients with refractory disease (progression during platinum-containing therapy) are ineligible.
* No more than 2-4 prior treatment regimens for Stage III/IV disease, defined as investigational, chemotherapy, hormonal, biologic, or targeted therapy.
* Prior doxorubicin (or other anthracycline) at a cumulative dose of ≤ 360 mg/m² or cumulative epirubicin dose of ≤ 720 mg/m² (calculated using doxorubicin equivalent doses: 1 mg of doxorubicin = 1 mg PLD = 0.3 mg mitoxantrone = 0.25 mg idarubicin). Subjects without any prior anthracycline exposure can also be included. Applies to Arm D only.
* At least 1 measurable lesion according to RECIST v1.1.
* Any prior palliative radiation therapy must be completed at least 7 days prior to start of study treatment and patients must have recovered from any acute adverse effects prior to start of study treatment.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 - 1.
* Baseline Laboratory Values:
1. ANC ≥1500/μL
2. HgB ≥ 9 g/dL with no blood transfusions in the past 28 days
3. Platelets ≥ 100,000/μL
4. ALT \& AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases
5. Serum bilirubin within normal limits (WNL) or ≤1.5 x the ULN in patients with liver metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert's Syndrome.
6. Serum creatinine ≤1.5 x the ULN and a calculated creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method.
* Left ventricular ejection fraction (LVEF) WNL of the institution as determined by multiple uptake gated acquisition (MUGA) or echocardiography (ECHO) (applies to Arm D only).
* Female patients, ≥18, (not of childbearing potential and fertile female patients of childbearing potential) who agree to use adequate contraceptive measures from 2 weeks prior to the study and until 1 month after study treatment discontinuation, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start.
* Predicted life expectancy ≥ 12 weeks
Exclusion
* Use of a study drug (approved or investigational drug therapy) ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of study treatment. For study drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the study drug and administration of study treatment is required.
* Major surgical procedures ≤ 28 days of beginning study, or minor surgical procedures ≤ 7 days. No waiting period following port-a-cath placement, or any other central venous access placement.
* Grade \>1 toxicity from prior therapy (except alopecia or anorexia).
* Known malignant CNS disease other than neurologically stable, treated brain metastases, defined as metastasis having no evidence of progression or haemorrhage after treatment for at least 2 weeks (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrolment.
* Patient has had prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be sensitive CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors or inducers of CYP3A4 which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks after last dose of study drug.
* Caution should be exercised when inhibitors or substrates of P-gP, substrates of CYP1A2 with a narrow therapeutic range, sensitive substrates of CYP2C19 or CYP2C19 substrates with a narrow therapeutic range are administered with adavosertib.
* Herbal medications should be discontinued 7 days prior to the first dose of study treatment.
* Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥ Class 2:
1. Unstable angina pectoris
2. Congestive heart failure
3. Acute myocardial infarction
4. Conduction abnormality not controlled with pacemaker or medication
5. Significant ventricular or supraventricular arrhythmias (patients with chronic rate controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
* Adavosertib should not be given to patients who have a history of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected. Adavosertib has not been studied in patients with ventricular arrhythmias or recent myocardial infarction.
* Corrected QT interval (QTc) \>470 msec at study entry or congenital long QT syndrome.
* Pregnant or lactating.
* Serious active infection at the time of enrolment, or another serious underlying medical condition that would impair the patient's ability to receive study treatment.
* Presence of other active cancers, or history of treatment for invasive cancer within 3 years. Patients with Stage I cancer who have received definitive local treatment within 3 years, and whom are considered unlikely to recur, are eligible. Patients with previously treated in-situ carcinoma (i.e., non-invasive) are eligible, as are patients with prior non-melanoma skin cancers.
18 Years
130 Years
FEMALE
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
AstraZeneca
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Kathleen Moore, MD
Role: PRINCIPAL_INVESTIGATOR
Stephenson Cancer Center, University of Oklahoma Health Sciences Center
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Research Site
Gilbert, Arizona, United States
Research Site
Tucson, Arizona, United States
Research Site
La Jolla, California, United States
Research Site
Los Angeles, California, United States
Research Site
San Francisco, California, United States
Research Site
Tampa, Florida, United States
Research Site
West Palm Beach, Florida, United States
Research Site
Augusta, Georgia, United States
Research Site
Boston, Massachusetts, United States
Research Site
Detroit, Michigan, United States
Research Site
New York, New York, United States
Research Site
New York, New York, United States
Research Site
Cleveland, Ohio, United States
Research Site
Oklahoma City, Oklahoma, United States
Research Site
Abington, Pennsylvania, United States
Research Site
Nashville, Tennessee, United States
Research Site
Dallas, Texas, United States
Research Site
Milwaukee, Wisconsin, United States
Research Site
Toronto, Ontario, Canada
Research Site
Amsterdam, , Netherlands
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Moore KN, Chambers SK, Hamilton EP, Chen LM, Oza AM, Ghamande SA, Konecny GE, Plaxe SC, Spitz DL, Geenen JJJ, Troso-Sandoval TA, Cragun JM, Rodrigo Imedio E, Kumar S, Mugundu GM, Lai Z, Chmielecki J, Jones SF, Spigel DR, Cadoo KA. Adavosertib with Chemotherapy in Patients with Primary Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer: An Open-Label, Four-Arm, Phase II Study. Clin Cancer Res. 2022 Jan 1;28(1):36-44. doi: 10.1158/1078-0432.CCR-21-0158. Epub 2021 Oct 13.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
Access external resources that provide additional context or updates about the study.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
GYN 49
Identifier Type: OTHER
Identifier Source: secondary_id
2015-000886-30
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
D6010C00004
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.