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

NCT03253679 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: NCI-2017-01498NCI1013610136UM1CA186688
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Advanced Malignant Solid Neoplasm; Refractory Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (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%.

  Up to 2 years 6 months

Secondary Outcomes (4)

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

  Up to 2 years 6 months

• To Evaluate Time Until Death or Disease Progression.

  Up to 2 years 6 months

• Duration of Responses

  Up to 2 years 6 months

• 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.

  Up to 2 years 6 months

Study Arms (1)

Treatment (adavosertib)

EXPERIMENTAL

Patients 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.

Drug: Adavosertib

Interventions

Adavosertib DRUG

Given PO

Also known as: AZD-1775, AZD1775, MK-1775, MK1775

Treatment (adavosertib)

Eligibility Criteria

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

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (9)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

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

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 36469840 DERIVED

MeSH Terms

Interventions

adavosertib

Results Point of Contact

• Title: Dr. Siqing Fu
• Organization: M D Anderson Cancer Center

siqingfu@mdanderson.org

713-792-4318

Study Officials

• Siqing Fu

  University of Texas MD Anderson Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2017
• First Posted: August 18, 2017
• Study Start: January 16, 2019
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: October 17, 2023
• Results First Posted: September 13, 2023

Record last verified: 2023-09

Locations

US (9)