Ensayos clínicos

Inclusion Criteria:

• 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 FGF/FGFR1-3 (gain of function mutations, translocations, and amplifications allowed) in tumor tissue or blood tested at a Clinical Laboratory Improvement Amendments (CLIA) – certified laboratory.
• Provide informed written consent.
• Age ≥ 18 years. Age = ________.
• 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;
  • Pembrolizumab;
  • Nivolumab;
  • 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 as defined:
  • A non-nodal lesion is considered measurable if its longest diameter can be accurately measured as ≥ 2.0 cm with chest x-ray, or as ≥ 1.0 cm with CT scan, or MRI;
  • A superficial non-nodal lesion is measurable if its longest diameter is ≥ 1.0 cm in diameter as assessed using calipers (e.g., skin nodules) or imaging. In the case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion, is recommended;
  • A malignant lymph node is considered measurable if its short axis is > 1.5 cm when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm).
  • NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease.
• ECOG Performance Status (PS) of 0, 1, or 2. Form is available on the ACCRU web site.
• ECOG Performance Status = ________.
• The following laboratory values obtained ≤ 28 days prior to registration:
• Earliest laboratory test date __ __/__ __/__ __ __ __; latest laboratory test date __ __/__ __/__ __ __ __. 
  • NOTE: These dates pertain to the following labs only:
    • Absolute neutrophil count (ANC) ≥ 1500/mm^3. ANC = _______;
    • Platelet count ≥ 100,000/mm^3. Platelet count = ________;
    • Hemoglobin ≥ 9.0 g/dL. Hemoglobin = ________;
    • Total bilirubin < 1.5 x upper limit of normal (ULN), or < 2.5 x ULN if patient has Gilbert syndrome or disease involving the liver.
• Does subject have Gilbert syndrome or disease involving the liver? (this question may be answered 1=Yes or 2=No).
  • ____ Yes. Total bilirubin (≤ 2.5 x ULN) = _______; ULN = _______.
  • ____ No. Total bilirubin (≤ 1.5 x ULN) = _______; ULN = _______.
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN (or <5 x ULN in presence of suspected liver metastases).
• Does subject have suspected liver metastases? (this question may be answered 1=Yes or 2=No).
  • ____ Yes. AST (≤ 5 x ULN) = _______; ULN = _______.
  •                 ALT (≤ 5 x ULN) = _______; ULN = _______.
  • ____ No. AST (≤ 2.5 x ULN) = _______; ULN = _______.
  •                 ALT (≤ 2.5 x ULN) = _______; ULN = _______.
• Serum phosphate < institutional ULN. Serum phosphate = _______; ULN = _______.
• 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).
  Which test was done to satisfy eligibility?
  ____ Serum calcium. Serum calcium = _______; LLN = _______; ULN = _______.
  ____ Serum albumin-corrected calcium = _______; LLN = _______; ULN = _______.
• Potassium levels > institutional lower limit of normal (supplementation can be used to correct potassium level during screening). Potassium = _______; LLN = _______.
• Serum creatinine < 1.5 x ULN, or calculated creatinine clearance >30 mL/min using the Cockcroft-Gault formula or 24-hours urine collection analysis.
  Which test was done to satisfy eligibility?
  ____ Serum creatinine. Serum creatinine = _______; ULN = _______.
  ____ Calculated creatinine clearance = _______.
• 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.
  See Appendix I for definition of WOCBP.
  If not a woman of childbearing potential or male (check NA)
  If a woman of childbearing potential – Negative serum pregnancy test date __ __/__ __/__ __ __ __.
• 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.

All responses in above section must be “Yes” unless specified as “NA.”

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-CNS disease <14 days prior to registration.
• External beam radiation therapy < 28 days prior to registration.
  If no prior external beam radiation therapy (check NA).
  If prior external beam radiation therapy - Last day of external beam radiation therapy.
  __ __/__ __/__ __ __ __
• Palliative radiation for non-CNS disease <14 days prior to registration.
  If no prior palliative radiation for non-CNS disease (check NA).
  If prior palliative radiation for non-CNS disease - Last day of palliative radiation for non-CNS disease.
  __ __/__ __/__ __ __ __
• 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 CTCAE 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:
  • Concomitant administration of potent CYP3A4 inhibitors and inducers and moderate CYP3A4 inducers. Based on the low overall bioavailability of topical ketoconazole, there are no restrictions on topical ketoconazole;
  • Any concomitant use of a selective FGFR inhibitor (other than Pemigatinib);
  • Investigational study drug for any indication;
  • Use of any anticancer medications (other than Pemigatinib).
• 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 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 (HBV) or hepatitis C (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.

All responses in above section must be “No” unless specified as “NA”.