Ovarian, Fallopian Tube, Peritoneal Cancer, P53 MutationPhase 2NCT02272790
Adavosertib Plus Chemotherapy in Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
A Phase 2 study testing Adavosertib, Paclitaxel and Carboplatin in people with Ovarian, Fallopian Tube, Peritoneal Cancer, P53 Mutation, run by AstraZeneca at 20 sites in 3 countries.
Trial summary
Adavosertib in combination with carboplatin, paclitaxel, gemcitabine, or PLD. Read more about this study
- Who is it for?
- Ages 18 to 130 years, women only
- Conditions the study is for
- Ovarian, Fallopian Tube, Peritoneal Cancer, P53 Mutation
- What is being tested?
- Adavosertib, Paclitaxel and Carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 20 sitesin 3 countries
- Study dates
- 30 Jan 2015to 8 Mar 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- 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
Who cannot join
- 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.
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- 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.
- 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.
Trial locations and contacts
20 sites in 3 countries.
20 sites in 3 countries
United States18 sites
Research Site
Abington, Pennsylvania, 19001
Research Site
Augusta, Georgia, 30912
Research Site
Boston, Massachusetts, 02215
Research Site
Cleveland, Ohio, 44195
Research Site
Dallas, Texas, 75390
Research Site
Detroit, Michigan, 48201
Research Site
Gilbert, Arizona, 85234
Research Site
La Jolla, California, 92093
Research Site
Los Angeles, California, 90024
Research Site
Milwaukee, Wisconsin, 53226
Research Site
Nashville, Tennessee, 37203
Research Site
New York, New York, 10019
Research Site
New York, New York, 10065
Research Site
Oklahoma City, Oklahoma, 73104
Research Site
San Francisco, California, 94158
Research Site
Tampa, Florida, 33612
Research Site
Tucson, Arizona, 85724
Research Site
West Palm Beach, Florida, 33401
About this study
Official title: A Multicentre Phase II Study of Adavosertib Plus Chemotherapy in Patients With Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Adavosertib in combination with carboplatin, paclitaxel, gemcitabine, or PLD.
Read the detailed description
This is an open-label, four-arm lead-in safety and efficacy study in which adavosertib will be combined in four separate treatment arms as follows: adavosertib plus gemcitabine (Arm A); adavosertib plus weekly paclitaxel (Arm B); adavosertib plus carboplatin (Arm C); and adavosertib plus PLD (Arm D). A subset of patients will be evaluated for the safety assessment of each treatment arm.
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.
- Being tested
- Adavosertib, Paclitaxel, Carboplatin, Gemcitabine, PLD
- Keywords
- Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdavosertibDrug
Also called MK1775
Adavosertib will be taken as oral capsules with water, approx. 2 hours before or 2 hours after food.
PaclitaxelDrug
Also called Taxol
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.
CarboplatinDrug
Also called Paraplatin
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.
GemcitabineDrug
Gemcitabine 800 mg/m² will be administered IV on Days 1, 8, and 15 of each 28-Day cycle.
PLDDrug
PLD (pegylated liposomal doxorubicin) 40 mg/m² IV will be given on Day 1 of each 28-Day cycle.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Adavosertib; Drug: PLD |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Throughout the duration of the study (up to 19 months)
Secondary outcomes (22)
Disease Control Rate (DCR)
The Disease Control Rate is defined as the proportion of patients achieving a complete response (CR), partial response (PR), or stable disease (SD) according to RECIST v1.1 criteria.
Measured: Throughout the duration of the study (up to 19 months)
Duration of Response (DoR)
Duration of Response (DoR) is defined as the time from first documented tumour response until the date of documented progression or death from any cause.
Measured: Throughout the duration of the study, approximately 19 months.
Progression Free Survival (Median, 80% CI)
Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment.
Progression-free survival was derived based on scan/assessment dates, not visit dates.
Measured: Throughout the Study, Approximately 4 years
Progression Free Survival (Median, 95% CI)
Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment.
Progression-free survival was derived based on scan/assessment dates, not visit dates.
Measured: Throughout the Study, Approximately 4 years
Overall Survival (Median, 80% CI)
Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive.
Measured: Throughout the Study, Approximately 4 years
Overall Survival (Median, 95% CI)
Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive.
Measured: Throughout the Study, Approximately 4 years
Gynecologic Cancer Intergroup (GCIG) CA-125 Response
The GCIG CA-125 response is defined as the proportion of patients achieving a 50% reduction in CA-125 levels from baseline, if baseline level is ≥2 x the upper limit of normal (ULN) within 2 weeks prior to starting treatment. Response must be confirmed and maintained for at least 28 days.
Measured: Throughout the study, approximately 4 years
The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade.
The number of patients experiencing at least one treatment-related adverse event (TEAE) by maximum CTCAE grade.
Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal
Measured: Throughout the duration of the study (up to 19 months)
The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade
The number and proportion of patients experiencing at least one treatment-related adverse event (TEAE) related to adavosertib by maximum CTCAE grade
Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal
Measured: Throughout the duration of the study (up to 19 months)
The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade
The number of patients experiencing at least one treatment-related adverse event (TEAE) related to chemotherapy by maximum CTCAE grade.
Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal
Measured: Throughout the duration of the study (up to 19 months)
Serious Adverse Events
The number of patients experiencing at least one serious adverse event (SAE).
Measured: Throughout the duration of the study (up to 19 months)
Serious Adverse Events Leading to Death
The number of patients experiencing at least one serious adverse event (SAE) leading to death.
Measured: Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation
The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment discontinuation.
Measured: Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction
The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to dose reduction.
Measured: Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption
The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment interruption.
Measured: Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation
The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment discontinuation.
Measured: Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction
The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to dose reduction.
Measured: Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption
The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment interruption.
Measured: Throughout the duration of the study (up to 19 months)
Single Dose Adavosertib Cmax
Maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin.
Measured: Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Multiple Dose Adavosertib Cmax
Maximum plasma concentration of adavosertib after a multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin.
Measured: Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Single Dose Adavosertib Tmax
The time to reach maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin.
Measured: Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Multiple Dose Adavosertib Tmax
The time to reach maximum plasma concentration of adavosertib after multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin.
Measured: Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2014 (estimated)
- Study start30 Jan 2015
- Primary completion13 Dec 2018
- Study completion8 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ovarian, Fallopian Tube, Peritoneal Cancer, P53 MutationStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kathleen Moore, MD, Principal investigator, Stephenson Cancer Center, University of Oklahoma Health Sciences Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02272790
- Sponsor's protocol ID
- D6010C00004
- Other IDs
- GYN 49, 2015-000886-30, 2015
- Status last verified
- Aug 2023
- First submitted
- 14 Oct 2014
- Last updated
- 3 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Publications
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.
PubMed 34645648
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre Phase II Study of Adavosertib Plus Chemotherapy in Patients With Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
- ClinicalTrials.gov ID
- NCT02272790
- Acronym / sponsor ID
- D6010C00004
- Keywords
- Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 30 Jan 2015 (actual)
- Primary completion
- 13 Dec 2018 (actual)
- Study completion
- 8 Mar 2023 (actual)
- First posted
- 23 Oct 2014 (estimated)
- Results
- Posted 22 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Adavosertib in combination with carboplatin, paclitaxel, gemcitabine, or PLD.
Detailed description
This is an open-label, four-arm lead-in safety and efficacy study in which adavosertib will be combined in four separate treatment arms as follows: adavosertib plus gemcitabine (Arm A); adavosertib plus weekly paclitaxel (Arm B); adavosertib plus carboplatin (Arm C); and adavosertib plus PLD (Arm D). A subset of patients will be evaluated for the safety assessment of each treatment arm.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm A (adavosertib + gemcitabine) | Experimental | Drug: Adavosertib, Drug: GemcitabineAdavosertib (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. |
| Arm B (adavosertib + paclitaxel) | Experimental | Drug: Adavosertib, Drug: PaclitaxelFive 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. |
| Arm C/C2 (adavosertib + carboplatin) | Experimental | Drug: Adavosertib, Drug: CarboplatinArm 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. |
| Arm D (adavosertib + PLD) | Experimental | Drug: Adavosertib, Drug: PLDFive 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. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdavosertibAlso: MK1775Adavosertib will be taken as oral capsules with water, approx. 2 hours before or 2 hours after food. | Drug | Arm A (adavosertib + gemcitabine), Arm B (adavosertib + paclitaxel), Arm C/C2 (adavosertib + carboplatin), Arm D (adavosertib + PLD) |
| PaclitaxelAlso: TaxolPaclitaxel 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. | Drug | Arm B (adavosertib + paclitaxel) |
| CarboplatinAlso: ParaplatinCarboplatin, 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. | Drug | Arm C/C2 (adavosertib + carboplatin) |
| GemcitabineGemcitabine 800 mg/m² will be administered IV on Days 1, 8, and 15 of each 28-Day cycle. | Drug | Arm A (adavosertib + gemcitabine) |
| PLDPLD (pegylated liposomal doxorubicin) 40 mg/m² IV will be given on Day 1 of each 28-Day cycle. | Drug | Arm D (adavosertib + PLD) |
Primary outcome
Objective Response Rate (ORR)
Time frame: Throughout the duration of the study (up to 19 months)
Objective response rate is defined as the proportion of patients achieving a complete or partial tumour response according to RECIST v1.1 criteria.
22 secondary outcomes
Disease Control Rate (DCR)
Time frame: Throughout the duration of the study (up to 19 months)
Duration of Response (DoR)
Time frame: Throughout the duration of the study, approximately 19 months.
Progression Free Survival (Median, 80% CI)
Time frame: Throughout the Study, Approximately 4 years
Progression Free Survival (Median, 95% CI)
Time frame: Throughout the Study, Approximately 4 years
Overall Survival (Median, 80% CI)
Time frame: Throughout the Study, Approximately 4 years
Overall Survival (Median, 95% CI)
Time frame: Throughout the Study, Approximately 4 years
Gynecologic Cancer Intergroup (GCIG) CA-125 Response
Time frame: Throughout the study, approximately 4 years
The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade.
Time frame: Throughout the duration of the study (up to 19 months)
The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade
Time frame: Throughout the duration of the study (up to 19 months)
The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade
Time frame: Throughout the duration of the study (up to 19 months)
Serious Adverse Events
Time frame: Throughout the duration of the study (up to 19 months)
Serious Adverse Events Leading to Death
Time frame: Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation
Time frame: Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction
Time frame: Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption
Time frame: Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation
Time frame: Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction
Time frame: Throughout the duration of the study (up to 19 months)
Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption
Time frame: Throughout the duration of the study (up to 19 months)
Single Dose Adavosertib Cmax
Time frame: Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Multiple Dose Adavosertib Cmax
Time frame: Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Single Dose Adavosertib Tmax
Time frame: Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Multiple Dose Adavosertib Tmax
Time frame: Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34645648Moore 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.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathleen Moore, MD principal investigator
Stephenson Cancer Center, University of Oklahoma Health Sciences Center
20 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Adavosertib, Paclitaxel and Carboplatin in people with Ovarian, Fallopian Tube, Peritoneal Cancer, P53 Mutation, run by AstraZeneca at 20 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Canada, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Throughout the duration of the study (up to 19 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02272790, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2023.