Selumetinib Sulfate in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer With KRAS G12R Mutations

NCT03040986 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: NCI-2017-0011817C014410050ZIABC011078
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 9

Brief Summary

This phase II trial studies how well selumetinib sulfate works in treating patients with pancreatic cancer with Kirsten rat sarcoma (KRAS) G12R mutations that has spread from where it started to nearby tissue or lymph nodes or other places in the body. Selumetinib sulfate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

KRAS NP_004976.2:p.G12R; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IV Pancreatic Cancer AJCC v6 and v7

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With an Objective Response (Partial Response + Complete Response)

  Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm (\<1 cm). Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  Approximately 1-8.2 months

Secondary Outcomes (17)

• Median Progression-free Survival (PFS)

  From start of treatment to time of progression or death, whichever occurs first, assessed up to 52 weeks

• Incidence of Grade 3 or Greater Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Probably or Definitely Attributable to the Agent Selumetinib

  Date treatment consent signed to date off study, approximately 25 months and 6 days.

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

  Date treatment consent signed to date off study, approximately 25 months and 6 days.

• Semi-quantitative Measurements of Connector Enhancer of the Kinase Suppressor of Ras-1 (CNKSR1)

  Up to 52 weeks

• Predictive Biomarkers for Response to Selumetinib

  Up to 52 weeks

Study Arms (1)

Treatment (selumetinib sulfate)

EXPERIMENTAL

Patients receive selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity

Other: Laboratory Biomarker Analysis; Drug: Selumetinib Sulfate

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (selumetinib sulfate)

Selumetinib Sulfate DRUG

Given by mouth (PO)

Also known as: AZD-6244 Hydrogen Sulfate, AZD6244 Hydrogen Sulfate, AZD6244 Hydrogen Sulphate, Selumetinib Sulphate

Treatment (selumetinib sulfate)

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 histologically confirmed locally advanced or metastatic pancreas cancer
• Patients must have received at least 6 months fluorouracil (5-FU)- or gemcitabine-based treatments for pancreas cancer (fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin \[FOLFIRINOX\], fluorouracil, leucovorin calcium and oxaliplatin \[FOLFOX\], 5-FU+ nal-IRI \[MM-398; nanoliposomal irinotecan\], or 5-FU \[including capecitabine\], gemcitabine-based gemcitabine plus abraxane, gemcitabine monotherapy among others)
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) with conventional techniques or as \>= 10 mm (\>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Patients must have Clinical Laboratory Improvement Act (CLIA) confirmed somatic Kirsten rat sarcoma (KRAS) G12R mutation as determined by sequence analysis of matched normal deoxyribonucleic acid (DNA) from any specimen obtained from the individual; patients must provide tumor sample for KRAS analysis or be willing to undergo mandatory screening biopsy
• Patients must not have had chemotherapy, molecular therapy with erlotinib, radiation therapy, or experimental biological or molecular therapy for at least 4 weeks prior to starting study medication; patients who received FOLFIRINOX must be 6 weeks from the last administration of therapy; patients must have recovered from any acute toxicity related to prior therapy or surgery, to a grade 1 or less unless specified
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 or Karnofsky \>= 70%
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 75,000/mcL
• Hemoglobin (Hgb) \>= 9.0 g/dL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) \< 3 x institutional upper limit of normal
• Creatinine =\< institutional upper limit of normal OR
• Creatinine clearance \> 60 mL/min/1.73 m\^2 by either Cockcroft-Gault formula or 24-hour urine collection analysis
• Patients must be willing to return to the clinic for follow-up visits

You may not qualify if:

• Patients who have received prior treatment with tyrosine kinase inhibitors (e.g. erlotinib), or anti-Epidermal growth factor receptor (EGFR) agents (e.g. cetuximab, panitumumab)
• Patients currently receiving any medication known to induce central serous chorioretinopathy which in the opinion of the principal investigator, would make the administration of study drug hazardous
• Patients with active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Any underlying medical condition which, in the opinion of the principal investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events
• Patients who are receiving any other investigational agents
• Patients with known brain metastases should be excluded from this clinical trial; no additional workup is needed to exclude brain metastases if the patient is asymptomatic or has no history of brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Selumetinib (AZD6244) or other agents used in study
• Previous Mitogen-activated protein kinase kinase (MEK), RAS, or Rapidly Accelerated Fibrosarcoma (RAF) inhibitor use
• Patients with the following cardiac conditions are excluded:
• Uncontrolled hypertension (blood pressure \[BP\] of \>= 150/95 despite medical support/management)
• Acute coronary syndrome within 6 months prior to starting treatment
• Uncontrolled angina - Canadian Cardiovascular Society grade II-IV despite medical support/management
• Heart failure New York Heart Association (NYHA) class II or above
• Prior or current cardiomyopathy (within 6 months) including but not limited to the following:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (9)

Los Angeles County-USC Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

NCI - Center for Cancer Research

Bethesda, Maryland, 20892, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• Kenney C, Kunst T, Webb S, Christina D Jr, Arrowood C, Steinberg SM, Mettu NB, Kim EJ, Rudloff U. Phase II study of selumetinib, an orally active inhibitor of MEK1 and MEK2 kinases, in KRASG12R-mutant pancreatic ductal adenocarcinoma. Invest New Drugs. 2021 Jun;39(3):821-828. doi: 10.1007/s10637-020-01044-8. Epub 2021 Jan 6.

  PMID: 33405090 DERIVED

Results Point of Contact

• Title: Dr. Udo Rudloff
• Organization: National Cancer Institute

udo.rudloff@nih.gov

240-760-6238

Study Officials

• Udo Rudloff

  National Cancer Institute 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: February 1, 2017
• First Posted: February 2, 2017
• Study Start: July 21, 2017
• Primary Completion: August 10, 2018
• Study Completion: October 15, 2020
• Last Updated: February 9, 2021
• Results First Posted: January 11, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)