A Phase 3 Multicenter, Open-Label, Randomized, Controlled Study of Oral Infigratinib Versus Gemcitabine With Cisplatin in Subjects With Advanced/Metastatic or Inoperable Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations: The PROOF Trial
Clinical Trial Information
Trial Contact: De Leon, Ma Theresa; Donaldson, Karin M
IRB No: WIRB W1917504
Protocol Abbrev: QBGJ398-301 PROOF
Principal Investigator: Omar R. Kayaleh, MD
Phase: Drug: Phase III
Age Group: Adult
Secondary Protocol No: QBGJ398-301
Treatment: Drug: Infigratinib Drug: Gemcitabine with Cisplatin
Therapies Involved: Chemotherapy
ClinicalTrials.gov ID: NCT03773302
The primary objective is to demonstrate non-inferiority (NI) of treatment with infigratinib versus gemcitabine with cisplatin based on centrally assessed progression-free survival (PFS) for subjects with advanced/metastatic or inoperable cholangiocarcinoma with fibroblast growth factor receptor 2 (FGFR2) gene fusions/ translocations.
Have histologically or cytologically confirmed non-resectable, recurrent, or metastatic cholangiocarcinoma. Subjects with gallbladder cancer or ampullary carcinoma are not eligible.
2. Have written documentation of local or central laboratory determination of FGFR2 gene fusions/translocations. Note: Central confirmation is not required prior to enrollment in study. However, subjects without central confirmation of FGFR2 gene fusions/translocations can continue the treatment at the investigator’s discretion, but will be replaced.
3. Have a representative tumor sample available for central FGFR2 fusion/translocation molecular testing. An archival tumor sample and associated pathology report may be submitted. However, if not available, a newly obtained tumor biopsy may be submitted instead.
4. Have full recovery from the following permitted prior treatments (as applicable):
a. A non-curative operation (i.e., R2 resection [with macroscopic residual disease] or palliative bypass surgery only)
b. Curative surgery with evidence of non-resectable 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 chemotherapy, provided the treatment was completed > 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 IRB/IEC.
9. Have recovered from AEs of previous systemic anti-cancer therapies to baseline or Grade 1, except for alopecia.
10. Are able to swallow and retain oral medication.
11. Are willing and able to comply with scheduled visits, treatment plan and laboratory tests.
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 post-menopausal 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 (e.g., hormonal therapy, prior chemotherapy).
WOCBP and males whose sexual partners are WOCBP must agree to use barrier contraception and a second form of highly effective contraception (Clinical Trials Facilitation Group, 2014) while receiving study drug and for 3 months following their last dose of study drug. Alternatively, total abstinence is also considered a highly effective contraception method when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Sexually active males must use a condom during intercourse while taking drug and for 3 months after the last dose of the study drug and should not father a child during this period. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner to prevent delivery of the drug via seminal fluid.