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Pemigatinib for the Treatment of Metastatic or Unresectable Colorectal Cancer Harboring FGFR Alterations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04096417
Recruitment Status : Not yet recruiting
First Posted : September 19, 2019
Last Update Posted : September 19, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Academic and Community Cancer Research United

Brief Summary:
This phase II trial studies how well pemigatinib works in treating patients with colorectal cancer with mutations (alterations) in a FGFR gene and that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Pemigatinib may stop the growth of tumor cells by blocking FGFR, which is needed for cell growth.

Condition or disease Intervention/treatment Phase
FGFR1 Gene Amplification FGFR1 Gene Mutation FGFR1 Gene Translocation FGFR2 Gene Amplification FGFR2 Gene Mutation FGFR2 Gene Translocation FGFR3 Gene Amplification FGFR3 Gene Mutation FGFR3 Gene Translocation Metastatic Colorectal Carcinoma Stage III Colorectal Cancer AJCC v8 Stage IIIA Colorectal Cancer AJCC v8 Stage IIIB Colorectal Cancer AJCC v8 Stage IIIC Colorectal Cancer AJCC v8 Stage IV Colorectal Cancer AJCC v8 Stage IVA Colorectal Cancer AJCC v8 Stage IVB Colorectal Cancer AJCC v8 Stage IVC Colorectal Cancer AJCC v8 Unresectable Colorectal Carcinoma Drug: Pemigatinib Other: Quality-of-Life Assessment Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

I. To assess overall response rate (ORR) of pemigatinib in patients with metastatic or unresectable colorectal cancer harboring activating FGFR alterations.

SECONDARY OBJECTIVES:

I. To assess the clinical benefit rate (complete response + partial response + stable disease) with pemigatinib.

II. To assess progression free survival (PFS) and overall survival (OS) with pemigatinib.

III. Assess changes in patient quality of life (QOL) as measured by the linear analogue self-assessment (LASA) questionnaire.

IV. Assess the frequency and severity of adverse events.

CORRELATIVE RESEARCH OBJECTIVES:

I. To assess plasma pharmacodynamic biomarkers of response and resistance to therapy.

II. To explore any correlation between tissue and blood based biomarkers and clinical outcomes.

OUTLINE:

Patients receive pemigatinib orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 3 years after registration.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Single-Arm Study of Pemigatinib in Patients With Metastatic or Unresectable Colorectal Cancer Harboring FGFR Alterations
Estimated Study Start Date : December 1, 2019
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : December 1, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (pemigatinib)
Patients receive pemigatinib PO QD on days 1-21. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.
Drug: Pemigatinib
Given PO
Other Name: INCB054828

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment




Primary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: At 36 weeks after registration ]
    Defined as the percentage of patients, among evaluable patients, who experience an objective response per RECIST 1.1. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper and Pearson.


Secondary Outcome Measures :
  1. Clinical benefit rate [ Time Frame: Up to 36 weeks after registration ]
    Clinical Benefit Rate is defined as the number of patients that experience a complete or partial response within 36 weeks post registration, or have stable disease for at least 36 weeks post registration, divided by the number of evaluable patients. Analysis of this endpoint will mirror that of the primary objective.

  2. Progression-free survival (PFS) [ Time Frame: From study entry to the first of either disease progression or death from any cause, assessed up to 3 years after registration ]
    Progression-free survival (PFS) is defined as the time from study entry to the first of either disease progression or death from any cause, where disease progression is determined based on RECIST 1.1 criteria. PFS will be estimated using the Kaplan-Meier method. The median PFS and corresponding 95% confidence interval will be reported. Patients who do not experience disease progression or death while on protocol will be censored at the last disease assessment date.

  3. Overall survival (OS) [ Time Frame: From study entry to death from any cause, assessed up to 3 years after registration ]
    Overall survival (OS) is defined as the time from study entry to death from any cause. Will be estimated using the Kaplan-Meier method. The median OS and corresponding 95% confidence interval will be reported.

  4. Quality of Life (QOL) as measured by the LASA [item 1: Overall QOL] [ Time Frame: From baseline up to 36 weeks ]
    Quality of Life (QOL) was measured using item 1: Overall QOL of the Linear Analogue Self-Assessment (LASA) Questionnaire on a 0-10 scale, with 0=as bad as it can be and 10=as good as it can be. The QOL scores was converted to a 100-point scale, with 0=Low QOL and 100=Best QOL. Change from baseline to Week 36 will be calculated by subtracting the baseline scores from the scores at Week 36. Negative change indicates the QOL decrease and positive change indicates the QOL improvement.

  5. Incidence of adverse events [ Time Frame: Up to 3 years after registration ]
    Adverse events will be summarized by frequency and severity using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Registered to Colorectal and Liquid Biopsy Molecularly Assigned Therapy (COLOMATE) Academic and Community Cancer Research United (ACCRU)-GI-1611 and:

    • COLOMATE Companion Trial Recommendation Form indicates patient qualifies to be screened for a COLOMATE companion trial
    • COLOMATE Companion Trial Recommendation Form date of completion is =< 30 days prior to registration
  • Histologically or cytologically confirmed diagnosis of metastatic or unresectable colorectal cancer (mCRC), based on documentation from local or outside review of pathology according to each site?s established institutional procedure
  • Documentation of an activating genomic alteration(s) in FGFR1-3 (gain of function mutations, translocations, and amplifications allowed)
  • Provide informed written consent
  • Patient must have received and progressed on, or be intolerant to, each of the following treatments for mCRC (or have contraindication to these treatments):

    • Fluoropyrimidine
    • Oxaliplatin
    • Irinotecan
    • Anti-VEGF (vascular endothelial growth factor) monoclonal antibody, if eligible for this therapy
    • Anti-EGFR (epidermal growth factor receptor) monoclonal antibody, if eligible for this therapy
  • Measurable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
  • Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 28 days prior to registration)
  • Platelet count >= 100,000/mm^3 (obtained =< 28 days prior to registration)
  • Hemoglobin >= 9.0 g/dL (obtained =< 28 days prior to registration)
  • Total bilirubin =< 1.5x upper limit of normal (ULN), or =< 2.5x ULN if patient has Gilbert syndrome or disease involving the liver (obtained =< 28 days prior to registration)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5x ULN (or =< 5x ULN in presence of suspected liver metastases) (obtained =< 28 days prior to registration)
  • Serum phosphate < institutional ULN (obtained =< 28 days prior to registration)
  • Serum calcium within institutional normal range, or serum albumin-corrected calcium within institutional normal range (if serum albumin is outside of the institutional normal range) (obtained =< 28 days prior to registration)
  • Potassium levels > institutional lower limit of normal (supplementation can be used to correct potassium level during screening) (obtained =< 28 days prior to registration)
  • Serum creatinine =< 1.5x ULN, or calculated creatinine clearance > 30 mL/min using the Cockcroft-Gault formula or 24-hours urine collection analysis (obtained =< 28 days prior to registration)
  • Corrected QT interval (QTc) by Fridericia?s method (QTcF) assessed by electrocardiogram (ECG) completed =< 28 days prior to registration, and resulted as:

    • QTcF =< 450 msec in men, or
    • QTcF =< 470 msec in women
  • Negative serum pregnancy test completed =< 7 days prior to registration, for women of childbearing potential only
  • Willing to provide tissue and blood samples for correlative research purposes
  • Willing to allow transfer of tissue and blood samples, clinical information, and outcome data collected from this trial for future research

Exclusion Criteria:

  • Prior treatment with pemigatinib
  • Prior treatment with a selective FGFR inhibitor =< 180 days (6 months) prior to registration
  • Known hypersensitivity or severe reaction to an FGFR inhibitor, or to the excipients of pemigatinib (i.e. microcrystalline cellulose, sodium starch glycolate, and magnesium stearate)
  • Current evidence of clinically significant corneal or retinal disorder confirmed by ophthalmologic examination
  • Treatment with other investigational study drug for any indication for any reason, or receipt of anticancer medications =< 14 days prior to registration
  • Major surgery =< 28 days prior to registration
  • External beam radiation therapy =< 28 days prior to registration, or palliative radiation for non-central nervous system (CNS) disease =< 14 days prior to registration
  • Brain metastases, central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression

    • NOTE: Patients who are asymptomatic or previously treated and stable, without evidence of progression for >= 28 days prior to registration are eligible
    • NOTE: Patients taking concomitant corticosteroids and/or anticonvulsants are allowed if patient is on a stable or decreasing dose of such treatment for >= 28 days prior to registration
  • History or presence of significant cardiovascular disease or condition including:

    • Uncontrolled angina pectoris (Canadian Cardiovascular Society grade II-IV despite medical therapy)
    • Congestive heart failure (New York Heart Association class III or IV)
    • Uncontrolled arrhythmia requiring therapy. Note: Patients with a pacemaker and well-controlled rhythm for >= 28 days prior to registration are not excluded
    • Any of the following occurring =< 6 months prior to registration: myocardial infarction, angioplasty, cardiac stenting, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack
  • Failure to adequately recover (i.e. to =< grade 1 [according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.)5] or to pre-treatment baseline) from adverse events (AEs) deemed by the investigator as clinically significant and attributed to prior therapy. Exception: alopecia
  • Current use of prohibited medication
  • Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers =< 14 days or 5 half-lives (whichever is shorter) prior to registration. Note: topical ketoconazole will be allowed
  • History of hypovitaminosis D requiring supraphysiologic doses to replenish the deficiency. Note: patients receiving vitamin D food supplements are allowed
  • History and/or current evidence of ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung; with the exception of calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcification
  • Unable or unwilling to swallow pemigatinib and keep a medication diary, or significant gastrointestinal disorder(s) that could interfere with absorption, metabolism or excretion of pemigatinib per the discretion of the investigator
  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

    • Pregnant women
    • Nursing women
    • Women of childbearing potential or men able to father children who have a female partner of childbearing potential, who are unwilling to employ acceptable contraception
  • Known history of human immunodeficiency (HIV) infection or positivity on immunoassay confirmed per local standards

    • Note: HIV test is not required for screening, but patients with a known history of HIV infection will be excluded
  • Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  • Other known active malignancy =< 5 years prior to registration

    • EXCEPTIONS: Non-melanotic skin cancer or carcinoma in situ of the cervix, provided there is no known active disease and no additional therapy for the condition is ongoing or required during the trial period
    • NOTE: anti-estrogen/androgen therapy or bisphosphonates allowed
  • Co-morbid systemic illness, other severe concurrent disease, or psychiatric illness/social situation which, in the judgment of the investigator, would make the patient inappropriate for entry into this study, limit compliance with study requirements, or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimen

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04096417


Locations
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United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
Contact: Laurie A. Mihalik    480-342-6140    mihalik.laurie@mayo.edu   
Principal Investigator: Tanios S. Bekaii-Saab         
United States, District of Columbia
MedStar Georgetown University Hospital
Washington, District of Columbia, United States, 20007
Contact: Brenton Foretich    202-687-4346    bjf53@georgetown.edu   
Principal Investigator: Benjamin A. Weinberg         
United States, Georgia
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Contact: Kim Nguyen    404-778-5680    kim.t.nguyen@emory.edu   
Principal Investigator: Bassel F. El-Rayes         
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
Contact: Heather Macauley    773-702-9251    hmacauley@bsd.uchicago.edu   
Principal Investigator: Daniel V. Catenacci         
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Contact: Jesse A. Huffman    314-747-6268    jessehuffman@wustl.edu   
Principal Investigator: Katrina S. Pedersen         
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Contact: Francisco J. Cordero    919-681-3095    francisco.cordero@duke.edu   
Principal Investigator: John H. Strickler         
United States, Tennessee
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Contact: Jennifer G. Whisenant    615-875-8630    j.whisenant@vumc.org   
Principal Investigator: Kristen K. Ciombor         
United States, Wisconsin
Aurora Cancer Care-Milwaukee West
Wauwatosa, Wisconsin, United States, 53226
Contact: Jennifer Mathieu    414-302-2312    jennifer.mathieu@aurora.org   
Principal Investigator: Federico Augusto H. Sanchez         
Sponsors and Collaborators
Academic and Community Cancer Research United
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Kristen K Ciombor Academic and Community Cancer Research United
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Responsible Party: Academic and Community Cancer Research United
ClinicalTrials.gov Identifier: NCT04096417    
Other Study ID Numbers: ACCRU-GI-1701
NCI-2019-05877 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ACCRU-GI-1701 ( Other Identifier: Academic and Community Cancer Research United )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: September 19, 2019    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Carcinoma
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases