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 aberrationsMedDRA version: 20.0Level: PTClassification code 10001150Term: Adenocarcinoma gastricSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-004505-27-IT
- Lead Sponsor
- Basilea Pharmaceutica International AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 47
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 antracycline 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 antracycline) for metastatic disease or locally advanced disease.
- TCS Group: Patients enrolled in the TCS Groups (of Cohort 3.1, 3.2 or 3.3) need to have disease that is safely amenable to biopsies.
6. Positive test for eligible FGFRfus/amp/mt status as per central testing.
7. For Substudies 1 and 3, 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 127
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 127
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 antiprogrammed cell death receptor-1 (PD-1) or anti-programmed death ligand-1 (PD-L1) therapeutic antibody or pathway-targeting agents.
5. Concurrent evidence of corneal or retinal disorder, 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: myocardial infarction, or New York Heart Association Class II to IV congestive heart failure, 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.
7. Any unresolved clinically-significant Common Terminology Criteria for Adverse Events (CTCAE) Grade =2 toxicity (except for alopecia, Grade 2 platinum-therapy-related neuropathy, and/or Grade 2 anemia, from previous anti-tumor treatment and/or from medical/surgical procedures/interventions).
8. Known central nervous system (CNS) metastases.
9. 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.
10. Concurrent uncontrolled or active infection with human immunodeficiency virus (HIV; known HIV 1/2 antibodies positive).
11. Active hepatitis B, or hepatitis C. Active hepatitis B is defined as a known positive hepatitis B surface antigen (HBsAg) result. Active hepatitis C is defined by a known positive hepatitis C antibody result and known quantitative hepatitis C virus (HCV) RNA results greater than the lower limits of detection of the assay.
12. Active tuberculosis.
...
22. Pregnant or breast feeding.
Applicable to patients considered for enrollment in Substudy 2 or 3:
23. Uncontrolled arterial hypertension, with a systolic blood pressure = 150 mm Hg or a diastolic blood pressure = 90 mm Hg despite standard medical management.
24. History of gastrointestinal perforation and/or fistulae within 6 months prior to study entry.
25. History of clinically relevant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal tract within 3 months prior to study entry.
26. 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.
27. The patient is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin, or similar agents.
28. Child-Pugh B or C liver cirrhosis.
Applicable only to patients considered for enrollment in Substudy 3:
29. Administration of a live, attenuated vaccine within 30 days prior to randomization.
30. Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to first
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