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Trial record 1 of 1 for:    CFGF401x2101
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FGF401 in HCC and Solid Tumors Characterized by Positive FGFR4 and KLB Expression

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ClinicalTrials.gov Identifier: NCT02325739
Recruitment Status : Recruiting
First Posted : December 25, 2014
Last Update Posted : December 18, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
Estimate the maximum tolerated dose and/or recommended phase II dose and efficacy of FGF401 as single agent and in combination with PDR001 in patients with hepatocellular carcinoma and as single agent in patients with other solid malignancies.

Condition or disease Intervention/treatment Phase
HCC Drug: FGF401 Biological: PDR001 Phase 1 Phase 2

Detailed Description:
Estimate the maximum tolerated dose and/or recommended phase II dose by detecting the Dose Limiting Toxicity and efficacy of FGF401 as single agent and in combination with PDR001 in patients with hepatocellular carcinoma and as single agent in patients with other solid malignancies based on RECIST 1.1.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 238 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, Multicenter, Open-label Study of Oral FGF401 in Adult Patients With Hepatocellular Carcinoma or Solid Malignancies Characterized by Positive FGFR4 and KLB Expression
Actual Study Start Date : December 29, 2014
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : May 15, 2019
Arms and Interventions

Arm Intervention/treatment
Experimental: FGF401 single agent
Approximately 168 patients enrolled
Drug: FGF401
FGF401 is a FGFR4 inhibitor.
Experimental: FGF401 in combination with PDR001
Approximately 70 patients enrolled
Drug: FGF401
FGF401 is a FGFR4 inhibitor.
Biological: PDR001
PDR001 is a humanized anti-PD1 IgG4 antibody that blocks the binding of PD-L1 and PD-L2


Outcome Measures

Primary Outcome Measures :
  1. Incidence rate of Dose-limiting Toxicity (DLT) [ Time Frame: Cycle 1 (21 days) for FGF401 single agent; Cycle 1 and Cycle 2 (42 days) for FGF401 in combination with PDR001 ]
    For Phase l parts only

  2. Time to progression (TTP) [ Time Frame: From baseline, then every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from study. Up to 6 months. ]
    FGF401 single agent-Phase II part - Group 1 and Group 2

  3. Overall response rate (ORR) [ Time Frame: From baseline, then every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from study. Up to 6 months. ]
    FGF401 single agent-Phase II part - Group 3 and FGF401 in combination with PDR001-Phase II


Secondary Outcome Measures :
  1. Number of adverse events (AEs)/serious adverse events (SAEs) [ Time Frame: Continuously throughout the study until 30 days after FGF401 discontinuation or 150 days after PDR001 discontinuation ]
    Incidence and severity of AEs, SAEs, changes in laboratory values, vital signs and ECGs, dose interruptions and reductions

  2. Best Overall Response (BOR)- phase I and phase II parts [ Time Frame: From baseline, then every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from study. Up to 6 months. ]
  3. Overall Response Rate (ORR)- phase I parts and FGF401 single agent phase II Group 1 and Group 2 and FGF401 in combination with PDR001 Phase II part [ Time Frame: From baseline, then every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from study. Up to 6 months. ]
  4. Disease Control Rate (DCR)- phase I and phase II parts [ Time Frame: From baseline, then every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from study. Up to 6 months. ]
  5. Time to Progression (TTP)- phase I parts and FGF401 in combination with PDR001 Phase II part [ Time Frame: From baseline, then every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from study. Up to 6 months. ]
  6. Overall Survival (OS)- phase I and phase II parts [ Time Frame: Start of study drug to Survival Endpoint, Average 9 months. ]
  7. Progression-free Survival (PFS)- FGF401 single agent phase II Group 3 and FGF401 in combination with PDR001 Phase II part [ Time Frame: From baseline, then every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from study. Up to 6 months. ]
  8. Plasma concentration of FGF401 [ Time Frame: During phase I parts: Cycle 1 Day 1, 2, 8, 9, 15, Cycle 2 Day 1, 2, Cycle 3 Day 1 and Cycle 4 Day 1; during phase II parts: Cycle 1 Day 1, 2, 8, 15, Cycle 2 Day 1, 2 and Day 1 of Cycle 3 to Cycle 6 ]
  9. Concentration of PDR001 [ Time Frame: For FGF401 in combination with PDR001 phase I part: C1 D1,8,15, C2 D1, C3 D1,15, D1 of Cycle 4 to 6, apprx. 10mo after C1D1, 150-day safety FU; and phase II part: Day 1 of Cycle 1 to 6, apprx. 10mo after C1D1 and 150-day safety FU ]
  10. Presence and/or concentration of anti-PDR001 antibodies [ Time Frame: For FGF401 in combination with PDR001 phase I and phase II parts: Day 1 of Cycle 1 to 6, apprx. 10mo after C1D1 and 150-day safety FU ]
  11. Cmax of PDR001 [ Time Frame: For FGF401 in combination with PDR001 phase I part: C1 D1,8,15, C2 D1, C3 D1,15, D1 of Cycle 4 to 6, apprx. 10mo after C1D1, 150-day safety FU; and phase II part: Day 1 of Cycle 1 to 6, apprx. 10mo after C1D1 and 150-day safety FU ]
  12. Cmin of PDR001 [ Time Frame: For FGF401 in combination with PDR001 phase I part: C1 D1,8,15, C2 D1, C3 D1,15, D1 of Cycle 4 to 6, apprx. 10mo after C1D1, 150-day safety FU; and phase II part: Day 1 of Cycle 1 to 6, apprx. 10mo after C1D1 and 150-day safety FU ]
  13. AUCinf of PDR001 [ Time Frame: For FGF401 in combination with PDR001 phase I part: C1 D1,8,15, C2 D1, C3 D1,15, D1 of Cycle 4 to 6, apprx. 10mo after C1D1, 150-day safety FU; and phase II part: Day 1 of Cycle 1 to 6, apprx. 10mo after C1D1 and 150-day safety FU ]
  14. AUClast of PDR001 [ Time Frame: For FGF401 in combination with PDR001 phase I part: C1 D1,8,15, C2 D1, C3 D1,15, D1 of Cycle 4 to 6, apprx. 10mo after C1D1, 150-day safety FU; and phase II part: Day 1 of Cycle 1 to 6, apprx. 10mo after C1D1 and 150-day safety FU ]
  15. AUCtau of PDR001 [ Time Frame: For FGF401 in combination with PDR001 phase I part: C1 D1,8,15, C2 D1, C3 D1,15, D1 of Cycle 4 to 6, apprx. 10mo after C1D1, 150-day safety FU; and phase II part: Day 1 of Cycle 1 to 6, apprx. 10mo after C1D1 and 150-day safety FU ]
  16. T1/2 of PDR001 [ Time Frame: For FGF401 in combination with PDR001 phase I part: C1 D1,8,15, C2 D1, C3 D1,15, D1 of Cycle 4 to 6, apprx. 10mo after C1D1, 150-day safety FU; and phase II part: Day 1 of Cycle 1 to 6, apprx. 10mo after C1D1 and 150-day safety FU ]
  17. Cmax of FGF401 [ Time Frame: During phase I parts: Cycle 1 Day 1, 2, 8, 9, 15, Cycle 2 Day 1, 2, Cycle 3 Day 1 and Cycle 4 Day 1; during phase II parts: Cycle 1 Day 1, 2, 8, 15, Cycle 2 Day 1, 2 and Day 1 of Cycle 3 to Cycle 6 ]
  18. Cmin of FGF401 [ Time Frame: During phase I parts: Cycle 1 Day 1, 2, 8, 9, 15, Cycle 2 Day 1, 2, Cycle 3 Day 1 and Cycle 4 Day 1; during phase II parts: Cycle 1 Day 1, 2, 8, 15, Cycle 2 Day 1, 2 and Day 1 of Cycle 3 to Cycle 6 ]
  19. AUCinf of FGF401 [ Time Frame: During phase I parts: Cycle 1 Day 1, 2, 8, 9, 15, Cycle 2 Day 1, 2, Cycle 3 Day 1 and Cycle 4 Day 1; during phase II parts: Cycle 1 Day 1, 2, 8, 15, Cycle 2 Day 1, 2 and Day 1 of Cycle 3 to Cycle 6 ]
  20. AUClast of FGF401 [ Time Frame: During phase I parts: Cycle 1 Day 1, 2, 8, 9, 15, Cycle 2 Day 1, 2, Cycle 3 Day 1 and Cycle 4 Day 1; during phase II parts: Cycle 1 Day 1, 2, 8, 15, Cycle 2 Day 1, 2 and Day 1 of Cycle 3 to Cycle 6 ]
  21. AUCtau of FGF401 [ Time Frame: During phase I parts: Cycle 1 Day 1, 2, 8, 9, 15, Cycle 2 Day 1, 2, Cycle 3 Day 1 and Cycle 4 Day 1; during phase II parts: Cycle 1 Day 1, 2, 8, 15, Cycle 2 Day 1, 2 and Day 1 of Cycle 3 to Cycle 6 ]
  22. T1/2 of FGF401 [ Time Frame: During phase I parts: Cycle 1 Day 1, 2, 8, 9, 15, Cycle 2 Day 1, 2, Cycle 3 Day 1 and Cycle 4 Day 1; during phase II parts: Cycle 1 Day 1, 2, 8, 15, Cycle 2 Day 1, 2 and Day 1 of Cycle 3 to Cycle 6 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. ECOG Performance Status ≤ 1
  2. Presence of at least one measurable lesion according to RECIST v1.1. c-i) FGF401 single agent-Phase I and Phase II, Group 3: Patients with HCC or advanced solid tumors, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists. c-ii) FGF401 single agent-Phase II, Groups 1 and 2: HCC patients previously treated with sorafenib for advanced HCC with documented disease progression during or after discontinuation of sorafenib treatment, or intolerance to sorafenib treatment c-iii) FGF401 in combination with PDR001:Advanced HCC patients who have received up to 2 previous lines of systemic treatment and one treatment must have included sorafenib with documented disease progression during or after discontinuation of sorafenib treatment, or intolerance to sorafenib treatment

Exclusion Criteria:

  1. Previous treatment with a selective FGF19-FGFR4 targeted therapy and/or pan-FGFR inhibitor.
  2. Symptomatic CNS metastases which are neurologically unstable or requiring increasing doses of steroids to control their CNS disease.
  3. Patient having out of range laboratory values defined as:

    • Hematology Hemoglobin ≤ 9 g/dL (SI Units: 90 g/L) Platelet count < 75000/mm3 Absolute neutrophil count (ANC) < 1500/mm3
    • Chemistry Total bilirubin ≥ 2 mg/dL AST and/or ALT > 3 x ULN Serum creatinine > 1.5 x ULN and/or creatinine clearance ≤ 45 mL/min
    • Coagulation: PT > 4 seconds more than ULN or INR > 1.7
  4. Pregnant or nursing (lactating) women.

Other protocol-defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02325739


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

  Show 27 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02325739     History of Changes
Other Study ID Numbers: CFGF401X2101
First Posted: December 25, 2014    Key Record Dates
Last Update Posted: December 18, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
FGF401, PDR001, PD-1, FGFR4, FGF19, HCC