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. Pemigatinib is an anti-cancer drug that acts on cells with alterations in the FGFR gene. It is used in Europe to treat people with biliary tract cancer who carry a specific FGFR alteration. However, in various clinical trials, pemigatinib has shown interesting activity in a number of patients with different cancers presenting with an alteration in the FGFR gene. This treatment could therefore be effective in several types of cancer where an alteration in the FGFR gene is detected. The aim of this clinical trial is to learn if pemigatinib works to treat patients with recurrent and/or metastatic cancer (whatever the type of cancer excluding blood cancers and those already treated with pemigatinib) presenting an alteration in the FGFR gene. Patients will: * Take oral pemigatinig in 3-week cycles (every day for 2 weeks followed by one week without pemigatinib) as long as they benefit from it. * Visit the clinic once every 3 weeks for checkups and tests during the treatment period * Visit the clinic once every 3 months for checkups after stopping treatment for at least 12 months.
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. All the patients included in this clinical trial will receive pemigatinib. The expected benefit for patient is the control of the disease through stabilization, reduction or even disappearance of the cancer and related symptoms. The risks are mainly related to the adverse effects of the drug. The regular monitoring offered by the hospital and the additional examinations (such as more regular X-ray examinations, eye tests and blood tests) may constitute constraints. However, this monitoring and these examinations are carried out in order to better monitor and treat the effects of pemigatinib for both patient safety and the course of the disease.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Pemigatinib will be administered orally once daily for 2 weeks followed by a 1-week off (intermittent schedule 2/1).
CHU de BREST
Brest, France
RECRUITINGCentre Antoine Lacassagne
Nice, France
ACTIVE_NOT_RECRUITINGInstitut Curie
Paris, France
NOT_YET_RECRUITINGCHU Poitiers
Poitiers, France
ACTIVE_NOT_RECRUITINGCHU Saint Etienne
Saint-Priest-en-Jarez, France
ACTIVE_NOT_RECRUITINGInstitut de Cancerologie de Lorraine
Vandœuvre-lès-Nancy, France
ACTIVE_NOT_RECRUITINGTumor regression
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 treatment (between the nadir and disease progression) and the slope of tumor growth before treatment. The sum of the diameters of target lesions according to RECIST 1.1 will be calculated on each patient's imaging by the Blinded Independent Central Review (BICR).
Time frame: From enrollment to disease progression, up to 42 months
Overall response rate (ORR)
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.
Time frame: From enrollment to the progression, up to 42 months
Clinical benefit rate (CBR)
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.
Time frame: From enrollment to the progression, up to 42 months
Duration of response (DoR)
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.
Time frame: From enrollment to the progression, up to 42 months
Progression-free survival (PFS)
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 frame: From enrollment to disease progression or death, up to 42 months
Time to treatment failure (TTF)
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.
Time frame: From enrollment to the end of treatment (or up to 42 months)
Overall survival (OS)
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.
Time frame: From enrollment to death (or up to 42 months)
Safety and tolerability of pemigatinib
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 scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.
Time frame: From enrollment to the end of treatment (up to 42 months)
Quality of life questionnaire - Core 30 (QLQ-C30)
Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
Time frame: At baseline, at 3 and 6 months during treatment and at the end of treatment
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