Clinical Trials /

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

NCT04096417

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pemigatinib for the Treatment of Metastatic or Unresectable Colorectal Cancer Harboring FGFR Alterations
  • Official Title: A Phase II, Multicenter, Single-Arm Study of Pemigatinib in Patients With Metastatic or Unresectable Colorectal Cancer Harboring FGFR Alterations

Clinical Trial IDs

  • ORG STUDY ID: ACCRU-GI-1701
  • SECONDARY ID: NCI-2019-05877
  • SECONDARY ID: ACCRU-GI-1701
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT04096417

Conditions

  • 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

Interventions

DrugSynonymsArms
PemigatinibINCB054828Treatment (pemigatinib)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pemigatinib)ExperimentalPatients 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.
  • Pemigatinib

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:At 36 weeks after registration
Safety Issue:
Description: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

Measure:Clinical benefit rate
Time Frame:Up to 36 weeks after registration
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Overall survival (OS)
Time Frame:From study entry to death from any cause, assessed up to 3 years after registration
Safety Issue:
Description: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.
Measure:Quality of Life (QOL) as measured by the LASA [item 1: Overall QOL]
Time Frame:From baseline up to 36 weeks
Safety Issue:
Description: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.
Measure:Incidence of adverse events
Time Frame:Up to 3 years after registration
Safety Issue:
Description:Adverse events will be summarized by frequency and severity using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Academic and Community Cancer Research United

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