A Phase 1b/2 study of derazantinib as monotherapy and combination therapy with paclitaxel, ramucirumab or atezolizumab in patients with HER2-negative gastric adenocarcinoma harboring FGFR genetic aberrations (FIDES-03)
- Conditions
- HER2-negative gastric adenocarcinoma harboring FGFR genetic aberrationsTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-004505-27-DE
- Lead Sponsor
- Basilea Pharmaceutica International Ltd., Allschwil
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 314
1. Informed consent signed by the patient indicating that they understand the purpose of, and procedures required for, the study, and are willing to participate in the study, prior to any study-related procedure.
2. Male or female aged = 18 years.
3. Histologically-confirmed adenocarcinoma of the gastro-esophageal junction or stomach.
4. Negative HER2 status obtained from the most recent available tissue sample.
5. Inoperable recurrent, locally-advanced adenocarcinoma or progressing stage IV adenocarcinoma of the gastro-esophageal junction or stomach, and prior antitumor treatment as specified for each Substudy:
? Substudy 1 : Patients with radiographically-documented disease progression after either standard first- or second-line treatment, and no approved treatment alternative.
? Substudy 2: Patients with radiographically-documented disease progression after standard first-line treatment, and per Investigator assessment considered suitable to tolerate the treatment regimen.
? Substudy 3: Patients with objective radiographically-documented disease progression:
- During, or within 6 months after, administration of the last cycle of adjuvant / neoadjuvant / perioperative chemotherapy (platinum plus fluoropyrimidine with or without anthracycline and/or taxane and/or irinotecan) for locally advanced disease, or
- During, or any time after, administration of the last cycle of first-line taxane-free chemotherapy (platinum plus fluoropyrimidine with or without anthracycline) for metastatic disease or locally advanced disease.
6. Eigible FGFRfus/amp/mt positive test result.
7. Measurable disease as defined by the Investigator using Response Evaluation Criteria in Solid Tumors 1.1 criteria (RECIST 1.1)
disease per RECIST 1.1 is not required for Substudy 2.
8. ECOG PS 0 or 1.
9. Adequate organ functions, as indicated by Screening visit local laboratory values
10. Men and women of childbearing potential must agree to avoid impregnating a partner or becoming pregnant, respectively, during the study, and for at least 150 days after the last dose of study drug.
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 157
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 157
1. Receipt of prior cancer treatment within specific interval periods (see Exclusion criterion 1).
2. For patients enrolled in Substudy 1, prior treatment with FGFR inhibitors.
3. For patients enrolled in Substudy 2 and 3, prior treatment with
- Taxanes within 6 months prior to randomization
- FGFR inhibitors or pathway-targeting agents
- Anti-VEGF(R) therapeutic antibody or pathway-targeting agents.
4. For patients enrolled in Substudy 3, prior treatment with anti-programmed cell death receptor-1 (PD-1) or anti-programmed death ligand-1 (PD-L1) therapeutic antibody or pathway-targeting agents.
5. Concurrent evidence of clinically significant corneal or retinal disorder likely to increase the risk of eye toxicity, including but not limited to bullous/band keratopathy, keratoconjunctivitis (unless keratoconjunctivitis sicca), corneal abrasion (unless related to trauma), inflammation/ulceration, confirmed by ophthalmological examination.
6. History of clinically significant cardiac disorders: New York Heart Association Class II to IV congestive heart failure, within 6 months of the first dose of study drug; any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months of the first dose of study drug, concurrent and clinically significant abnormalities on electrocardiogram [ECG] at Screening, including a QT interval corrected by Fridericia’s formula [QTcF]1 > 450 ms for males or > 460 ms for females (mean values from triplicate ECGs).
7. Any unresolved clinically-significant Common Terminology Criteria for Adverse Events (CTCAE) Grade = 2 toxicity. (Exception: patients with alopecia, Grade =2 platinum-therapy related neuropathy, or Grade = 2 anemia from previous anti-tumor treatment and/or from medical/surgical procedures/interventions, may be enrolled).
8. Known central nervous system (CNS) metastases.
...
18. Pregnant or breast feeding.
Applicable to patients considered for enrollment in Substudy 2 or 3:
19. Concurrent uncontrolled or active infection with human immunodeficiency virus (HIV, known HIV 1/2 antibodies positive)
20. Active hepatitis or chronic hepatitis B without current antiviral therapy and an HBV DNA = 100 IU/mL.
21. Active hepatitis C.
22. Active tuberculosis
23. Lack of recovery from major surgery after 4 weeks, or major elective surgery is planned during the foreseeable duration of the patient's participation in the study, or placement of a central venous access device within 7 days prior to randomization.
24. Uncontrolled arterial hypertension, with a systolic blood pressure = 150 mm Hg or a diastolic blood pressure = 90 mm Hg despite standard medical management.
25. History of gastrointestinal perforation and/or fistulae within 6 months prior to study entry.
26. History of clinically relevant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal tract within 3 months prior to study entry.
27. History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered ‘significant’) during the 3 months prior to randomization.
28. The patient is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin, or similar agents.
29. The patient is receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs, e.g. indomethacin, ibuprofen, naproxen,
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