Clinical trial NCT04383210: Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors
Official title: CRESTONE: A Phase 2 Study of Seribantumab in Adult Patients With Neuregulin-1 (NRG1) Fusion Positive Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Locally Advanced Solid Tumor
Metastatic Solid Tumor
Pancreatic Cancer
Lung Cancer
Head and Neck Cancer
Breast Cancer
Kidney Cancer
Colorectal Cancer
Bladder Cancer
Ovarian Cancer
Sarcoma
Gallbladder Cancer
Bile Duct Cancer
Esophageal Cancer
Uterine Cancer
Cholangiocarcinoma
Prostate Cancer
Keywords: NRG1
Neuregulin 1
Gene fusion
Lead sponsor: Elevation Oncology
Sponsor class: INDUSTRY
First posted: 2020-05-12
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is an open-label, international, multi-center, Phase 2 study in adult patients with recurrent, locally-advanced or metastatic solid tumors, which harbor the NRG1 gene fusion.


Eligibility criteria: Inclusion Criteria:

To be eligible for participation in the study, patients must meet the following inclusion criteria:

* Locally-advanced or metastatic solid tumor with an NRG1 gene fusion identified through molecular assays, such as PCR, NGS (RNA or DNA) or FISH, by a CLIA-certified or similarly accredited laboratory
* Availability of fresh or archived FFPE tumor sample to be submitted to a central laboratory for confirmation of NRG1 gene fusion status
* Patients should have received a minimum of one prior standard therapy appropriate for their tumor type and stage of disease, progressed or been nonresponsive to these available therapies, with no further available curative therapy options
* ≥ 18 years of age
* ECOG performance status (PS) 0, 1 or 2
* Patients must have at least one measurable extra-cranial lesion as defined by RECIST v1.1
* Adequate hepatic function defined as:
* Serum AST and serum ALT \< 2.5 × upper limit of normal (ULN), or AST and ALT \< 5 × ULN if liver function abnormalities due to underlying malignancy
* Total bilirubin \< 2.0 ULN. Subjects with a known history of Gilberts Disease and an isolated elevation of indirect bilirubin are eligible
* Adequate hematologic status, defined as:
* Absolute neutrophil count (ANC) ≥1.5 × 109/L not requiring growth factor support for at least 7 days prior to Screening, and
* Platelet count ≥100.0×109/L not requiring transfusion support for at least 7 days prior to Screening
* Able to provide informed consent or have a legal representative able and willing to do so
* Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation
* Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following study completion; this may include barrier methods such as condom or diaphragm with spermicidal gel.

Exclusion Criteria:

* Known, actionable oncogenic driver mutation other than NRG1 fusion where available standard therapy is indicated
* Life expectancy \< 3 months
* Pregnant or lactating
* Prior treatment with ERBB3/HER3 directed therapy (Cohort 1 only)
* Prior treatment with pan-ERBB or any ERBB/HER2/HER3 directed therapy (Cohort 1 only)
* Symptomatic or untreated brain metastases (Note: Patients with asymptomatic brain metastases treated with radiation or surgery and without evidence of progression by imaging at screening are eligible to participate in the study. Patients requiring ongoing corticosteroids to treat brain metastases will not be eligible).
* Received other investigational agent or anticancer therapy within 28 days prior to planned start of seribantumab or 5 half-lives, whichever is shorter
* Prior to initiation of seribantumab treatment, patients must have recovered from clinically significant toxicities from prior anticancer or investigational therapy
* Any other active malignancy requiring systemic therapy
* Known hypersensitivity to any of the components of seribantumab or previous CTCAE grade 3 or higher hypersensitivity reactions to fully human monoclonal antibodies
* Clinically significant cardiac disease, including symptomatic congestive heart failure, unstable angina, acute myocardial infarction within 12 months of planned first dose, or unstable cardiac arrhythmia requiring therapy (including torsades de pointes)
* Active uncontrolled systemic bacterial, viral, or fungal infection
* Patients who are not appropriate candidates for participation in this clinical study for any other reason as deemed by the investigator

Primary outcomes:
measure: Objective Response Rate
timeFrame: Up to 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: HonorHealth
state: Arizona
city: Fountain Valley
country: United States
facility: Compassionate Care Research Group Inc.
state: California
city: Huntington Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Orange
country: United States
facility: University of California - Irvine Medical Center
state: California
city: Denver
country: United States
facility: University of Colorado Denver
state: Colorado
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants
state: Delaware
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Athens
country: United States
facility: University Cancer And Blood Center
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Cancer Care
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford
state: Michigan
city: Saint Louis Park
country: United States
facility: Metro Minnesota CCOP
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Health Hershey Medical Center Cancer Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Oncology Clinic
state: South Dakota
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Blacksburg
country: United States
facility: Oncology & Hematology Associates of Southwest Virginia Inc., DBA Blue Ridge Cancer Care
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Appleton
country: United States
facility: ThedaCare Regional Cancer Center
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Sydney
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research Ltd.
state: Western Australia
city: Vancouver
country: Canada
facility: BC Cancer
state: British Columbia
city: Brampton
country: Canada
facility: William Osler Health System
state: Ontario
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
References: