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Advanced Malignant Solid NeoplasmPhase 2NCT03253679

AZD1775 in Treating Patients With Advanced Refractory Solid Tumors With CCNE1 Amplification

A Phase 2 study testing Adavosertib in people with Advanced Malignant Solid Neoplasm and Refractory Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial studies how well AZD1775 works in treating patients with solid tumors with CCNE1 amplification that have spread to other places in the body (advanced) and do not respond to treatment (refractory). AZD1775 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Adavosertib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
9 sitesUnited States
Study dates
16 Jan 2019to 31 Oct 2022
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have one of the histologically advanced solid tumors harboring CCNE1 amplification: Their diseases are refractory to, or do not have, standard-of-care therapy; or they declined standard-of-care therapy; CCNE1 amplification is defined in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory: CCNE1 amplification > 7 based on targeted custom Ampliseq panel on the Ion Torrent Personal Genoma Machine (PGM); or CCNE1 amplification on alternate CLIA platforms such as Foundation One, University of Washington (UW)-OncoPlex-Cancer Gene Panel, Memorial Sloan Kettering (MSK)-Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT), Solid Tumor Genomic Assay (Life Technologies), etc. will also be eligible to be treated after principal investigator (PI) approval; patients with known CCNE1 amplification on local or commercial platforms can start treatment after planned biopsy or submission of recent archival sample; central next generation sequencing (NGS) CCNE1 and fluorescence in-situ hybridization (FISH) testing will be performed to confirm the result
  • Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • Has read and understands the informed consent form (ICF) and has given written ICF prior to any study procedures; patients with impaired decision making capacity (IDMC) must have a close caregiver or legally authorized representative (LAR)
  • Any prior radiation must have been completed at least 7 days prior to the start of study drugs, and patients must have recovered from any acute adverse effects prior to the start of study treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1
  • Absolute neutrophil count (ANC) >= 1500/uL (within 14 days of study drug[s] initiation)
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  • Hemoglobin (HgB) >= 9 g/dL for mono-therapy (within 14 days of study drug[s] initiation)
  • Platelets >= 100,000/uL (within 14 days of study drug[s] initiation)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN) or =< 5 x ULN if known hepatic metastases (within 14 days of study drug[s] initiation)
  • Serum bilirubin < ULN or < 1.5 x ULN in patients with liver metastases; or total bilirubin < 3.0 x ULN with direct bilirubin within normal limits (WNL) in patients with well documented Gilbert's syndrome (within 14 days of study drug[s] initiation)
  • Serum creatinine =< 1.5 x ULN, or calculated creatinine clearance (CrCl) >= 45 mL/min as calculated by the Cockcroft-Gault method or 24-hour measured urine CrCl >= 45 mL/min (within 14 days of study drug[s] initiation)
  • Female patients who are not of child-bearing potential and fertile females 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 3 days prior to the start of study treatment; male patients willing to abstain or use barrier contraception (i.e. condoms) for the duration of the study and for 3 months after treatment stops
  • Willingness and ability to comply with study and follow-up procedures
  • Ability to take oral medications without medical history of malabsorption or other chronic gastrointestinal disease, or other conditions that may hamper compliance and/or absorption of the study agent
  • No prior treatment with wee1 kinase inhibition
  • Provision of an archival tissue block, or 10 formalin-fixed paraffin-embedded (FFPE) slides, if available, and if not available having biopsiable disease and agreeing to pre-treatment biopsies

Who cannot join

  • Use of anti-cancer treatment drug =< 21 days or 5 half-lives (whichever is shorter) prior to the first dose of AZD1775; for drugs for which 5 half-lives is =< 21 days, a minimum of 10 days between termination of the prior treatment and administration of AZD1775 treatment is required
  • Previous radiation therapy completed =< 7 days prior to the start of study drugs
  • Major surgical procedures =< 28 days of beginning AZD1775, or minor surgical procedures =< 7 days; no waiting period required following port-a-cath or other central venous access placement
  • Unresolved grade 2 toxicity from prior therapy (except alopecia or anorexia)
  • Patient has an inability to swallow oral medications; Note: Patient may not have a percutaneous endoscopic gastrostomy (PEG) tube or be receiving total parenteral nutrition (TPN)
  • No other anticancer-therapy (chemotherapy, immunotherapy, hormonal anti-cancer therapy, radiotherapy [except for palliative local radiotherapy]), biological therapy or other novel agent is to be permitted while the patient is receiving study medication; patients on luteinizing hormone-releasing hormone (LHRH) analogue treatment for more than 6 months are allowed entry into the study and may continue at the discretion of the investigator
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  • Known malignant central nervous system (CNS) disease other than neurologically stable, treated brain metastases - defined as metastasis having no evidence of progression or hemorrhage for at least 2 weeks after treatment; 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 known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued 2 weeks prior to day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug; co-administration of aprepitant or fosaprepitant during this study is prohibited; the use of sensitive substrates of CYP3A4, such as atorvastatin, simvastatin and lovastatin, is also prohibited in this study
  • Herbal preparations are not allowed throughout the study; these herbal medications include but are not limited to: St. John's wort, kava, ephedra (ma hung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto and ginseng; patients should stop using these herbal medications 7 days prior to first dose of study treatment
  • Any known hypersensitivity or contraindication to the components of the study drug AZD1775
  • 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)
  • Mean resting corrected QTc interval using the Fridericia formula (QTcF) > 450 msec/male and > 470 msec/female (as calculated per institutional standards) obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart at study entry, or congenital long QT syndrome
  • Pregnant or breastfeeding women
  • Serious active infection at the time of study entry, or another serious underlying medical condition that would impair the ability of the patient to receive study treatment
  • Symptomatic and uncontrolled metastasis in the central nervous system or leptomeningeal or lymphangitic carcinomatosis
  • Presence of other active invasive cancers that do not harbor CCNE1 amplification
  • Grade 2 or higher peripheral neuropathy
  • Human immunodeficiency virus requiring highly active antiretroviral therapy (HAART) treatment due to unknown drug-drug interactions or has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive or C virus [e.g., hepatitis C virus (HCV) RNA (quantitative) is detected]) infection

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • University of Florida Health Science Center - Gainesville

    Gainesville, Florida, 32610

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: A Phase 2 Study of AZD1775, a Wee1 Inhibitor, in Patients With CCNE1 Amplification

This phase II trial studies how well AZD1775 works in treating patients with solid tumors with CCNE1 amplification that have spread to other places in the body (advanced) and do not respond to treatment (refractory). AZD1775 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the proportion of patients with the objective response rate (ORR) to adavosertib (AZD1775) in patients with advanced refractory cancers with CCNE1 amplification.

SECONDARY OBJECTIVES:

  1. To evaluate the proportion of patients alive and progression free at 6 months of treatment with AZD1775 in patients with advanced refractory cancers with CCNE1 amplification.

II. To evaluate proportion of patients with extended time to progression (time to progression on AZD1775/ time to progression on last line of therapy >= 1.3).

III. To evaluate time until death or disease progression. IV. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

OUTLINE:

Patients receive adavosertib orally (PO) once daily (QD) on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

Being tested
Adavosertib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AdavosertibDrug

    Also called AZD-1775, AZD1775, MK-1775, MK1775

    Given PO

Study groups in NCT03253679
Study groupRoleWhat they receive
Treatment (adavosertib)ExperimentalPatients receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Adavosertib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR)

    ORR is defined as a complete response or partial response and consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria. The ORR rate will be compared against a null benchmark value of 5%.

    Measured: Up to 2 years 6 months

Secondary outcomes (4)

  1. To Evaluate the Proportion of Patients Alive and Progression Free of Treatment With AZD1775 in Patients With Advanced Refractory Cancers With CCNE1 Amplification.

    Estimated using the Kaplan-Meier Method.

    Measured: Up to 2 years 6 months

  2. To Evaluate Time Until Death or Disease Progression.

    Estimated using the Kaplan-Meier Method.

    Measured: Up to 2 years 6 months

  3. Duration of Responses

    (time to progression on AZD1775/ time to progression on last line of therapy >= 1.3).

    Measured: Up to 2 years 6 months

  4. Identify Potential Predictive Biomarkers Beyond the Genomic Alteration by Which Treatment is Assigned or Resistance Mechanisms Using Additional Genomic, RNA, Protein and Imaging-based Assessment Platforms.

    Immunohistochemistry, reverse phase protein arrays, and next generation sequencing for targeted exome panel are used to reveal potential biomarkers predicting major clinical outcomes, and potential mechanisms of acquired resistance by comparing molecular signatures at baseline versus at time of relapse in responders.

    Measured: Up to 2 years 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Aug 2017
  2. Study start16 Jan 2019
  3. Primary completion31 Oct 2022
  4. Study completion31 Oct 2022

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03253679
Sponsor's protocol ID
NCI-2017-01498
Other IDs
NCI-2017-01498, NCI10136, 10136, 10136, UM1CA186688
Status last verified
Sep 2023
First submitted
17 Aug 2017
Last updated
17 Oct 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Fu S, Yao S, Yuan Y, Previs RA, Elias AD, Carvajal RD, George TJ, Yuan Y, Yu L, Westin SN, Xing Y, Dumbrava EE, Karp DD, Piha-Paul SA, Tsimberidou AM, Ahnert JR, Takebe N, Lu K, Keyomarsi K, Meric-Bernstam F. Multicenter Phase II Trial of the WEE1 Inhibitor Adavosertib in Refractory Solid Tumors Harboring CCNE1 Amplification. J Clin Oncol. 2023 Mar 20;41(9):1725-1734. doi: 10.1200/JCO.22.00830. Epub 2022 Dec 5.

    PubMed 36469840

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Adavosertib in people with Advanced Malignant Solid Neoplasm and Refractory Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 9 sites in United States.

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 16 inclusion and 23 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 17 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 9 sites in United States. 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 13 Sep 2023). 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: Up to 2 years 6 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 NCT03253679, 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 17 Oct 2023.

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