Adavosertib Plus Chemotherapy in Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

NCT02272790 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: D6010C00004GYN 492015-000886-30
• Study Type: interventional
• Target: 95
• Locations: 3 countries
• Sites: 20

Brief Summary

Adavosertib in combination with carboplatin, paclitaxel, gemcitabine, or PLD.

Conditions

Ovarian, Fallopian Tube, Peritoneal Cancer, P53 Mutation

Keywords

Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective response rate is defined as the proportion of patients achieving a complete or partial tumour response according to RECIST v1.1 criteria.

  Throughout the duration of the study (up to 19 months)

Secondary Outcomes (22)

• Disease Control Rate (DCR)

  Throughout the duration of the study (up to 19 months)

• Duration of Response (DoR)

  Throughout the duration of the study, approximately 19 months.

• Progression Free Survival (Median, 80% CI)

  Throughout the Study, Approximately 4 years

• Progression Free Survival (Median, 95% CI)

  Throughout the Study, Approximately 4 years

• Overall Survival (Median, 80% CI)

  Throughout the Study, Approximately 4 years

Study Arms (4)

Arm A (adavosertib + gemcitabine)

EXPERIMENTAL

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.

Drug: Adavosertib; Drug: Gemcitabine

Arm B (adavosertib + paclitaxel)

EXPERIMENTAL

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.

Drug: Adavosertib; Drug: Paclitaxel

Arm C/C2 (adavosertib + carboplatin)

EXPERIMENTAL

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.

Drug: Adavosertib; Drug: Carboplatin

Arm D (adavosertib + PLD)

EXPERIMENTAL

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.

Drug: Adavosertib; Drug: PLD

Interventions

Adavosertib DRUG

Adavosertib will be taken as oral capsules with water, approx. 2 hours before or 2 hours after food.

Also known as: MK1775

Arm A (adavosertib + gemcitabine); Arm B (adavosertib + paclitaxel); Arm C/C2 (adavosertib + carboplatin); Arm D (adavosertib + PLD)

Paclitaxel DRUG

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.

Also known as: Taxol

Arm B (adavosertib + paclitaxel)

Carboplatin DRUG

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.

Also known as: Paraplatin

Arm C/C2 (adavosertib + carboplatin)

Gemcitabine DRUG

Gemcitabine 800 mg/m² will be administered IV on Days 1, 8, and 15 of each 28-Day cycle.

Arm A (adavosertib + gemcitabine)

PLD DRUG

PLD (pegylated liposomal doxorubicin) 40 mg/m² IV will be given on Day 1 of each 28-Day cycle.

Arm D (adavosertib + PLD)

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has read and understands the informed consent form (ICF) and has given written IC prior to any study specific procedures.
• 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:
• ANC ≥1500/μL
• HgB ≥ 9 g/dL with no blood transfusions in the past 28 days
• Platelets ≥ 100,000/μL
• ALT \& AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases
• 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.
• Serum creatinine ≤1.5 x the ULN and a calculated creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method.

You may not qualify if:

• 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:
• Unstable angina pectoris
• Congestive heart failure
• Acute myocardial infarction
• Conduction abnormality not controlled with pacemaker or medication
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (20)

Research Site

Gilbert, Arizona, 85234, United States

Location

Research Site

Tucson, Arizona, 85724, United States

Location

Research Site

La Jolla, California, 92093, United States

Location

Research Site

Los Angeles, California, 90024, United States

Location

Research Site

San Francisco, California, 94158, United States

Location

Research Site

Tampa, Florida, 33612, United States

Location

Research Site

West Palm Beach, Florida, 33401, United States

Location

Research Site

Augusta, Georgia, 30912, United States

Location

Research Site

Boston, Massachusetts, 02215, United States

Location

Research Site

Detroit, Michigan, 48201, United States

Location

Research Site

New York, New York, 10019, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Cleveland, Ohio, 44195, United States

Location

Research Site

Oklahoma City, Oklahoma, 73104, United States

Location

Research Site

Abington, Pennsylvania, 19001, United States

Location

Research Site

Nashville, Tennessee, 37203, United States

Location

Research Site

Dallas, Texas, 75390, United States

Location

Research Site

Milwaukee, Wisconsin, 53226, United States

Location

Research Site

Toronto, Ontario, M5G 2M9, Canada

Location

Research Site

Amsterdam, 1066 CX, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 34645648 DERIVED

Related Links

• Related Info
• Related Info
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MeSH Terms

Interventions

adavosertib; Paclitaxel; Carboplatin; Gemcitabine; 1-dodecylpyridoxal

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Pejvack Motlagh, MD
• Organization: AstraZeneca

pejvack.motlagh@astrazeneca.com

+44 (0) 7384 799 850

Study Officials

• Kathleen Moore, MD

  Stephenson Cancer Center, University of Oklahoma Health Sciences Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2014
• First Posted: October 23, 2014
• Study Start: January 30, 2015
• Primary Completion: December 13, 2018
• Study Completion: March 8, 2023
• Last Updated: October 3, 2023
• Results First Posted: November 22, 2019

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (18); CA (1); NL (1)