The PROOF Trial
- Conditions
- CholangiocarcinomaMedDRA version: 20.0Level: PTClassification code 10008593Term: CholangiocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004004-19-IT
- Lead Sponsor
- QED Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 384
1. Have histologically or cytologically confirmed unresectable locally advanced or metastatic cholangiocarcinoma. Subjects with gallbladder cancer or ampulla of Vater carcinoma are not eligible.
2. Have written documentation of local laboratory or central laboratory determination of FGFR2 gene fusions/translocations from tumor tissue collected before treatment.
3. Have an archival tissue sample available with sufficient tumor for central FGFR2 fusion/translocation molecular testing. However, if an archival tissue sample is not available, a newly obtained (before
randomization) tumor biopsy may be submitted instead. If written documentation of FGFR2 fusion/translocation in tumor tissue is available from the central laboratory, an additional tumor sample does not need to
be submitted for central FGFR2 fusion/translocation molecular testing.Note: All enrolled subject must have determination of FGFR2 gene fusions/translocations by the central laboratory as confirmation of local
laboratory testing, but this central confirmation is not required prior toenrollment in the study.
4. Have full recovery from the following permitted prior treatments (as applicable) such that the subject is reasonably expected to toleratestudy treatment (gemcitabine/cisplatin or infigratinib) according to the
investigator's assessment:
a. A non-curative operation (ie., R2 resection [with macroscopic residualdisease] or palliative bypass surgery only)
b. Curative surgery with evidence of unresectable disease relapse requiring systemic chemotherapy
c. Adjuvant radiotherapy (with or without radio-sensitizing low-dose chemotherapy) for localized disease provided there has been clear evidence of disease progression before inclusion in this study
d. Adjuvant or neoadjuvant chemotherapy, provided recurrence afterdate of completion of therapy was = 6 months before trial entry
e. Photodynamic treatment provided there is clear evidence of disease
progression at the local site or at a new metastatic site.
5. Are = 18 years of age of either gender.
6. Have an Eastern Cooperative Oncology Group (ECOG) performance
status = 1.
7. Have a life expectancy > 3 months.
8. Are able to read and/or understand the details of the study and provide written evidence of informed consent as approved by Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
9. Are able to swallow and retain oral medication.
10. Are willing and able to comply with scheduled visits, treatment plan and laboratory tests.
11. If a woman of childbearing potential (WOCBP), must have a negative pregnancy test within 7 days of the first dose of study drug. A woman is not of childbearing potential if she has undergone surgical
sterilization (total hysterectomy, or bilateral tubal ligation or bilateral oophorectomy at least 6 weeks before taking study drug) or if she is postmenopausal and has had no menstrual bleeding of any kind including menstrual period, irregular bleeding, spotting, etc., for at least 12 months, with an appropriate clinical profile, and there is no other cause of amenorrhea (eg., hormonal therapy, prior chemotherapy).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 191
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 193
1.Have received treatment with any systemic anti-cancer therapy for unresectable locally, advanced or metastatic cholangiocarcinoma. Prior neoadjuvant or adjuvant therapy is permitted if documented disease
recurrence occurred = 6 months after the last date of neoadjuvant or adjuvant therapy.
2.Have history of a liver transplant.
3 Have previously or currently is receiving treatment with a mitogenactivated protein kinase MEK or selective FGFR inhibitor.
4.Have neurological symptoms related to underlying disease requiring increasing doses of corticosteroids. Note: Steroid use for management of central nervous system tumors is allowed but must be at a stable dose for at least 2 weeks preceding study entry.
5.Have a history of another primary malignancy within 3 years exceptadequately treated in situ carcinoma of the cervix or non-melanoma carcinoma of the skin or any other curatively treated malignancy that is
not expected to require treatment for recurrence during the course of the study.
6.Have any other medical condition that would, in the investigator's judgment, prevent the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
7.Have current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, inflammation or ulceration, keratoconjunctivitis, confirmed by ophthalmic examination.
Subjects with asymptomatic ophthalmic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study.
8.Have a history and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys,intestine, myocardium, vascular system and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification.
9.Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (eg., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption
syndrome, small bowel resection).
10.Have current evidence of endocrine alterations of calcium/phosphate homeostasis, eg., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc.
11.Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Subjects are not permitted toreceive enzyme-inducing anti-epileptic drugs, including carbamazepine, phenytoin, phenobarbital, and primidone.
12.Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges or products containing juice of these fruits within 7 days prior to first dose of study drug.
13.Have used medications known to prolong the QT interval and/or are associated with a risk of Torsades de Pointes (TdP) 7 days prior to first dose of study drug.
14.Have used amiodarone within 90 days prior to first dose of study drug.
15.Have insufficient bone marrow function:
a.Absolute neutrophil count (ANC) <1,000/mm3 (1.0 × 109/L)
b.Platelets <100,000/mm3 (<100× 109/L)
c.Hemoglobin <9.0 g/dL
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method