Efficacy of Pemigatinib in Patients With Solid Tumors Characterized by an Alteration of the Gene FGFR in Tumor Cells
- Registration Number
- NCT06653777
- Lead Sponsor
- UNICANCER
- Brief Summary
Alterations in the fibroblast growth factor receptor (FGFR) gene are involved in the development of cancer. These anomalies are found at very variable frequencies (from less than 1% to around 10%) in cancers of the bile ducts, bladder, uterus, brain, ovary, lung, airways, digestive tract, breast, etc.
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- Detailed Description
Anti-cancer treatments targeting abnormalities in the FGFR gene are currently marketed for biliary tract and bladder cancers, having demonstrated a certain degree of efficacy. In clinical trials, these drugs have shown promising signs of efficacy in other types of cancer with the same FGFR gene alterations.
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Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 40
- Histologically or cytologically confirmed solid tumor
- Patient with locally recurrent unresectable and/or advanced or metastatic disease harbouring a FGFR1,2,3 fusion/rearrangement or mutation
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- Patient for whom there is no appropriate therapeutic alternative and for whom a FGFR inhibitor is indicated by the institution or the regional multidisciplinary consultation meeting and who may derive a benefit, according to the physician assessment
- Estimated life expectancy >3 months
- Measurable disease according to response evaluation criteria in solid tumours version 1.1 (RECIST1.1), whatever the disease location. Tumor lesions located in a previously irradiated area, or in an area subjected to other loco-regional therapy, are considered measureable if progression has been clearly demonstrated in the lesion.
- Availability of 2 pre-treatment tumor evaluations performed with an interval of at least 4 weeks and no more than 3 months between the examinations (CT or MRI, but same technics for both) and without any cancer treatment during this period
- Patient with a minimal trend at 0.1 mm/day increase in tumor growth kinetics between pre-treatment and baseline scan, as assessed by the investigator
- Adequate hematologic function: Absolute neutrophil count (ANC) > 1.5 x 10⁹ /L; platelets > 75 x 10⁹ /L; haemoglobin > 9.0 g/dL. Transfusion is allowed with a 2-week washout period before treatment initiation
- Adequate hepatic function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2,5 x upper limit of normal (ULN) (≤ 5 x ULN for liver metastasis); total bilirubin < 1.5 x ULN (< 2.5 x ULN if Gilbert's syndrome or liver metastasis); alkaline phosphatase (ALP) < 3 x ULN
- Adequate renal function: serum creatinine clearance > 30 mL/minute based on Cockcroft-Gault formula
- Value of serum phosphate ≤ ULN and value of serum calcium within institutional normal range (or serum albumin-corrected calcium within normal range when serum albumin is outside of the normal range)
- Potassium levels within institutional normal range; supplementation can be used to correct potassium level during the screening.
- Men, and women of childbearing potential must agree to use adequate contraception for the duration of trial participation and for at least one week after the last dose of pemigatinib. Men must also agree to not donate sperm and women must agree to not donate oocytes during the specified period
- Women of childbearing potential must have a negative serum pregnancy test performed within 14 days before treatment initiation
- Patient is affiliated to a social security system
- Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in signing the patient's consent
- Hematologic malignancies
- Known hypersensitivity or severe reaction to pemigatinib or excipients of pemigatinib
- Patient with a disease and a FGFR alteration covered by a marketed indication for any selective FGFR inhibitor (e.g cholangiocarcinoma with FGFR2-fusion or a FGFR mutation are not eligible, while FGFR1 or 3 fusion are eligible)
- Patient who received prior selective FGFR inhibitor
- Patient who can be included in a recruiting study assessing FGFR inhibitor (including pemigatinib)
- Current evidence of clinically significant corneal or retinal disorder as confirmed by ophthalmologic examination
- Other current malignancy, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for 5 years or more and are deemed at negligible risk for recurrence, are eligible for the trial
- History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues such as skin, kidney tendon, or vessels due to injury, disease, or aging in the absence of systemic mineral imbalance)
- Significant gastrointestinal disorder(s) that could interfere with absorption, metabolism, or excretion of pemigatinib
- Inability to swallow and retain oral medication
- Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug/treatment administration, New York Heart Association Class III or IV congestive heart failure, and uncontrolled arrhythmia (participants with pacemaker or with atrial fibrillation and well-controlled heart rate are allowed)
- History or presence of an abnormal electrocardiogram that, in the investigator's opinion, is clinically meaningful. A screening QTcF interval > 480 ms is excluded.
- Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (defined as elevated transaminases or cirrhosis); chronic HBV/HCV infection with no cirrhosis and no elevated transaminases is allowed
- Known HIV infection except if undetectable viral load
- Other active chronic or current infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment within 2 weeks before enrollment (participants with asymptomatic chronic infections on prophylactic treatment are allowed)
- Prior anticancer therapy, including radiotherapy, endocrine therapy, immunotherapy, chemotherapy or other investigational agents within the last 4 weeks (6 weeks for nitrosoureas and mitomycin C). A 1-week washout is permitted for palliative radiation to non-central nervous system disease. Patients must have recovered (≤ Grade 1) from AEs from previously administered therapies or local treatments before treatment initiation (excluding alopecia, anemia and decreased creatinine clearance)
- Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or five half-lives (whichever is shorter) before the first dose of study drug
- Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol
- Inability or unlikeliness of the participant to comply with the dose schedule or with the medical evaluations and follow-up required by the trial because of geographic, familial, social, or psychological reasons
- Women who are pregnant or breastfeeding
- History of hypovitaminosis D requiring supraphysiologic doses (eg, 50,000 international unit (IU)/weekly) to replenish the deficiency.
- Participation in another therapeutic trial within the 30 days prior to inclusion
- Individuals deprived of liberty or placed under protective custody or guardianship
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description pemigatinib Pemigatinib Pemigatinib will be administered orally once daily for 2 weeks followed by a 1-week off (intermittent schedule 2/1).
- Primary Outcome Measures
Name Time Method Tumor regression From enrollment to disease progression, up to 42 months Proportion of patients experiencing an objective response or at least a 30% decrease in tumor growth kinetics at disease progression on study treatment as compared to the one calculated from the two pre-treatment tumor evaluations. The tumor kinetics variation is measured by the tumor growth ratio defined as the ratio of the slope of tumor growth on treatmen...
- Secondary Outcome Measures
Name Time Method Overall response rate (ORR) From enrollment to the progression, up to 42 months ORR is defined as the proportion of patients with a complete response (CR) or a partial response (PR) as best overall response during the study, based on RECIST1.1, as assessed by the BICR and by the physician.
Clinical benefit rate (CBR) From enrollment to the progression, up to 42 months CBR defined as the proportion of patients with a CR, a PR, or a stable disease (SD) lasting ≥ 24 weeks (6 months) as best overall response during the study, based on RECIST1.1, as assessed by the BICR and by the physician.
Duration of response (DoR) From enrollment to the progression, up to 42 months Duration of response (DoR) measured in responder patients from the time of first documented response (CR or PR) until the first documented disease progression (according to RECIST1.1) or death due to any cause, as assessed by the BICR and by the physician.
Progression-free survival (PFS) From enrollment to disease progression or death, up to 42 months PFS measured from the date of inclusion to the date of event defined as the first documented disease progression (according to RECIST1.1) or death from any cause, whichever occurs first as assessed by the BICR and by physicians. Patients with no event at the time of analysis will be censored at the date of last adequate tumor assessment.
Time to treatment failure (TTF) From enrollment to the end of treatment (or up to 42 months) TTF defined as the time from the date of inclusion to the date of permanent study treatment discontinuation (any cause, including disease progression, treatment toxicity and death, withdrawal of consent). Patients without treatment failure at the time of the analysis will be censored at the date of last tumor assessment.
Overall survival (OS) From enrollment to death (or up to 42 months) OS measured from the date of inclusion to the date of death from any cause. Patients who are alive at the time of analysis (including lost to follow-up) will be censored at the date of last contact.
Safety and tolerability of pemigatinib From enrollment to the end of treatment (up to 42 months) Safety and tolerability, as assessed by the occurrence of treatment-emergent and treatment-related adverse events according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5). The NCI-CTCAE v5 is widely accepted in the community of oncology research as the leading rating scale for adverse events. This sca...
Quality of life questionnaire - Core 30 (QLQ-C30) At baseline, at 3 and 6 months during treatment and at the end of treatment Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.
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Trial Locations
- Locations (1)
Institut Curie
🇫🇷Paris, France