Pemigatinib therapy for patients with solid tumors previously treated with FGF-R inhibitor

JRCT ID: jRCTs041230105

Registered date:16/11/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: advanced solid tumors with FGF-R1 or FGF-R2 amplification FGF-R3 mutation or other FGF-R alteration
• Date of first enrollment: 16/11/2023
• Target sample size: 1
• Study type: Interventional
• Intervention(s): Pemigatinib 13.5 mg is administered orally for 14 days, followed by a 7-day rest period. This cycle should be repeated.

Outcome(s)

• Primary Outcome: Best overall effect up to 16 weeks after treatment initiation
• Secondary Outcome: Progression-free survival (PFS) using the principal investigator's (co-principal investigator's) assessment, best overall response over the entire treatment period, and safety

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Patients have histologically/cytologically confirmed advanced solid tumors with amplification of the FGF-R1 or FGF-R2 gene, mutation of the FGF-R3 gene, or other FGF-R alterations, and there is no effective standard of care to be implemented.
2) Patients who have received an FGF-R inhibitor other than pemigatinib for at least 6 months and have achieved an SD or better response.
3) Patients over 20 years of age on the date of enrollment.
4) ECOG performance status (PS) of ECOG is 0-1.
5) Patients with measurable or unmeasurable (but evaluable) lesions as defined by RECIST ver1.1. In the case of endocrine tumors, endocrine laboratory findings may also be evaluated.
6) There is no effective standard treatment for the disease.
7) Adequate bone marrow function with the most recent laboratory values within 14 days prior to registration (same day of the week two weeks prior to registration date is acceptable) meeting all of the following
1Absolute neutrophil count (ANC) greater than or equal to1,500 /mm3
2Platelet count greater than or equal to 7.5 x 104 /mm3 (No blood transfusion within 14 days prior to blood collection for the test used for registration)
3Hemoglobin level greater than or equal to 10.0 g/dL
8) Adequate hepatic and renal function with the most recent laboratory values within 14 days prior to enrollment (the same day of the week two weeks prior to enrollment is acceptable) meeting all of the following
1Total bilirubin less than or equal to ULN x 1.5
2AST (GOT) less than or equal to ULN x 2.5 (or less than or equal to 5 times ULN if liver metastases are observed)
3ALT (GPT) less than or equal to ULN x 2.5 (or less than or equal to 5 times ULN if liver metastases are present)
4Serum creatinine level less than or equal to ULN
5Measured or estimated creatinine clearance (Ccr) greater than or equal to LLN x 75%.
The Cockcroft-Gault equation is used for estimation.
6Proteinuria less than or equal to Grade 1 (dipstick or 24-hour urine test)
9) The most recent laboratory values within 14 days prior to enrollment (the same day of the week two weeks prior to the date of enrollment is acceptable) with calcium and phosphorus homeostasis that meets all of the following.
1Serum inorganic phosphorus (Pi) level less than or equal to ULN x 1.5
2Normal serum ionized calcium (iCa) level
10) Cardiac function with the most recent laboratory values within 28 days prior to enrollment (the same day of the week 4 weeks prior to the date of enrollment is acceptable) meeting all of the following.
1New York Heart Association (NYHA) cardiac function classification less than or equal to II degree
2Left cardiac ejection fraction greater than or equal to 45%
3QTc interval less than or equal to 470 msec
(Note: The use of medications to normalize blood pressure and heart rate is permitted during the study period.)
11) All adverse events (other than those listed below) from prior systemic anticancer therapy have resolved to baseline or grade 1 or less.
1Alopecia
2Peripheral neuropathy that has developed as a result of prior anticancer therapy and is stable at grade 2 or less
12) The patient is able to understand the contents of the consent explanation document approved by the Accredited Clinical Research Review Board and the Patient-proposed health services Evaluation Committee, and the patient has given his/her written consent to participate in the study.

Exclude criteria

1)Has a primary or metastatic central nervous system (CNS) tumor.
2)Presence of or history of endocrine changes related to calcium-phosphorus homeostasis (e.g., epithelioid dysfunction, history of epithelioidectomy, tumor disruption, neoplastic calcinosis)
3)Presence or history of ectopic mineral deposits/calcifications (excluding lymph node calcification and asymptomatic coronary artery calcification) in (but not limited to) clinically significant soft tissues, kidney, intestinal tract, myocardium, lung, etc.
4)Findings of corneal disorders or keratopathy, including (but not limited to) bullous/zonal keratopathy, corneal detachment, inflammation/ulceration, or keratoconjunctivitis, are confirmed by ophthalmologic examination. However, this does not apply if the ophthalmologist determines that the findings due to keratoconus are clinically acceptable.
5)The patient is using a drug known to have the following effects, which cannot be discontinued or changed to another drug prior to the start of study drug administration (with the exception of the drug in eligibility criterion 2)
1Use within 7 days prior to the first dose of study drug of drugs with QT interval prolongation or risk of inducing torsade de pointes (TdP).
2Use of drugs that increase serum concentrations of phosphorus or calcium.
6)Clinically significant cardiac disease or cardiac dysfunction, including.
1Clinically significant cardiac disease such as congestive heart failure (CHF) requiring treatment, arterial hypertension with resting blood pressure (average of three consecutive measurements) exceeding 140/100 mmHg.
2Clinically significant cardiac arrhythmia, atrial fibrillation, or conduction abnormalities such as congenital QT interval prolongation syndrome or grade 2 or greater AV block/complete AV block, or a history of grade 3 or greater hyperkalemia or complications within 6 months before screening
3History of acute coronary syndrome within 6 months prior to screening (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], coronary angioplasty, coronary artery stenting)
4Complete left bundle branch block
5Right bundle branch block + left anterior hemiblock (LAHB) (2 bundle blocks)
7)History of radiotherapy extending beyond 30% of bone marrow reserve.
8)Pregnant or lactating women (pregnant women are defined as women from conception to the end of pregnancy and confirmed by a positive hCG [human chorionic gonadotropin] test)
9)Have a disease or condition other than those listed above (e.g., uncontrolled diabetes, infection/inflammation, bowel obstruction, inability to take capsules) that the principal investigator determines is likely to make participation in the study difficult due to safety issues or noncompliance with study procedures.
10)Women of childbearing potential (all women of physiological fertility) who do not use the following highly effective contraceptive methods during pemigatinib treatment and for 28 days after completion of treatment.
1Sterilization
2Sterilization of the male partner (at least 6 months prior to screening)
3Any combination of any two of the following (a and b, a and c, or b and c)
a.Contraception by hormonal medication, injections*, or implants*, or the use of other hormonal contraceptive methods (vaginal ring, transdermal patch*, etc.) with similar efficacy (<1% failure rate).
b.Intrauterine devices (IUDs) or intrauterine contraceptive systems (IUS).
c.Barrier contraceptive method: condom or occlusive cap (pessary or cervical cap*) combined with spermicide (foam*/gel*/film*/cream*/vaginal suppository).
*Not approved in Japan
If 12 months of spontaneous amenorrhea have already passed with the appropriate clinical profile (appropriate age, experience of vasomotor symptoms, etc.), the patient is considered to be perimenopausal and therefore not fertile. The woman is not considered to be of childbearing potential if she has undergone bilateral oophorectomy (not necessarily hysterectomy) or tubal ligation for more than 6 weeks. However, in the case of ovariectomy alone, the woman shall be considered not of childbearing potential after her reproductive status has been confirmed by evaluation of postoperative hormone levels.
11)Males of childbearing potential who do not use a condom during intercourse during pemigatinib treatment and for 28 days after completion of treatment. The woman must not become pregnant during the same period. Men who have had a vasectomy should also use a condom to avoid exposure of their partner to the study drug via semen.
12)Current evidence of clinically significant corneal (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis) or retinal disorder (including but not limited to macular/retinal degeneration, diabetic retinopathy, and retinal detachment) as confirmed by ophthalmologic examination
13)Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug. Moderate CYP3A4 inhibitors are not prohibited but should be avoided.
14)History of hypovitaminosis D requiring supraphysiologic doses (eg, 50,000 UI/weekly) to replenish the deficiency. Vitamin D supplements are allowed.
15)The patients who is known to have established resistance mutations to FGFR inhibitor or patients with radiological and clinical PD to prior FGFR inhibitor therapy other than pemigatinib.

Related Information

• Primary Sponsor: Ando Yuichi