Testing AZD1775 in Advanced Solid Tumors That Have a Mutation Called SETD2

NCT03284385 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2017-0167010170UM1CA186689
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 29

Brief Summary

This phase II trial studies how well adavosertib works in treating patients with SETD2-deficient solid tumors that have spread to other places in the body (advanced/metastatic). Adavosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Clear Cell Renal Cell Carcinoma; Locally Advanced Clear Cell Renal Cell Carcinoma; Locally Advanced Malignant Solid Neoplasm; Metastatic Malignant Solid Neoplasm; Metastatic Renal Cell Carcinoma; Stage III Renal Cell Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. The median duration of response will be descriptively reported using Kaplan-Meier product limit method along with 95% confidence interval. The objective response rate between cohorts will be compared using the chi-squared test.

  Up to 2 years

Secondary Outcomes (5)

• Clinical benefit rate

  Up to 2 years

• Duration of response

  Up to 2 years

• Incidence and severity of adverse events

  Up to 2 years

• H3K36me3 mark

  Up to 2 years

• Progression free survival

  Up to 2 years

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, AZD-1775, AZD1775, MK 1775, 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:

• Cohort A: Histologically confirmed locally advanced or metastatic solid tumor malignancy other than clear cell renal cell carcinoma with progression on at least one prior systemic therapy and presence of pathogenic loss of SETD2 detected in tumor tissue detected using a Clinical Laboratory Improvement Act (CLIA)-certified next generation sequencing panel (e.g. UCSF500, FoundationOne)
• Cohort B: Patients with histologically confirmed locally advanced or metastatic clear cell renal cell carcinoma (with clear cell component on pathology), who have been treated with at least one prior systemic therapy for locally advanced or metastatic disease, including either tyrosine kinase inhibitor and/or immune checkpoint inhibitor, with evidence of SETD2 mutation on CLIA-certified next generation sequencing panel
• All next generation sequencing (NGS) sequencing reports will be reviewed by the University of California at San Francisco (UCSF) Molecular Tumor Board to verify pathogenicity of SETD2 mutation. Each NGS report will be redacted for Protected Health Information (PHI) prior to submission from investigational site to UCSF MTB.
• Measurable disease by RECIST 1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL
• Total bilirubin within normal institutional limits (WLN) or =\< 1.5 x upper limit of normal (ULN) in patients with liver metastases; or total bilirubin =\< 3 x ULN with direct bilirubin WLN in patients with well documented Gilbert's syndrome
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3.0 x institutional upper limit of normal (=\< 5 x ULN if known liver metastases)
• Serum creatinine =\< 1.5 x ULN, OR
• Creatinine clearance \>= 45 ml/min (24 hour urine creatinine clearance or calculated by Cockcroft-Gault equation)
• 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
• 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

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 study treatment, or minor surgical procedures =\< 7 days; no waiting period required following port-a-cath or other central venous access placement
• Grade \> 1 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 enrollment; patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• Any known hypersensitivity or contraindication to the components of the study drug AZD1775
• 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; transporter studies (in vitro) have shown that AZD1775 is an inhibitor of breast cancer resistance protein (BCRP); 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 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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (29)

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

MedStar Georgetown University Hospital

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

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, 60451, United States

Location

University of Chicago Medicine-Orland Park

Orland Park, Illinois, 60462, United States

Location

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334, United States

Location

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376, United States

Location

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

Location

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, 63136, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, 37204, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Maldonado E, Rathmell WK, Shapiro GI, Takebe N, Rodon J, Mahalingam D, Trikalinos NA, Kalebasty AR, Parikh M, Boerner SA, Balido C, Krings G, Burns TF, Bergsland EK, Munster PN, Ashworth A, LoRusso P, Aggarwal RR. A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170). Cancer Res Commun. 2024 Jul 1;4(7):1793-1801. doi: 10.1158/2767-9764.CRC-24-0213.

  PMID: 38920407 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasm Metastasis

Interventions

adavosertib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Rahul R Aggarwal

  Yale University Cancer Center LAO

  PRINCIPAL INVESTIGATOR

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: September 14, 2017
• First Posted: September 15, 2017
• Study Start: January 29, 2019
• Primary Completion: March 1, 2026
• Study Completion (Estimated): April 22, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (29)