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FGF401 in HCC and Solid Tumors Characterized by Positive FGFR4 and KLB Expression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02325739
Recruitment Status : Completed
First Posted : December 25, 2014
Last Update Posted : January 10, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 172 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
Actual Primary Completion Date : May 30, 2019
Actual Study Completion Date : May 30, 2019

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




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: 5 years ]
    FGF401 single agent-Phase II part - Group 1 (HCC, Asians) and Group 2 (HCC, non-Asians)

  3. Overall response rate (ORR) [ Time Frame: 5 years ]
    FGF401 single agent-Phase II part - Group 3 (non-HCC, other solid tumors) 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: 5 years ]
  3. Overall Response Rate (ORR)- phase I parts and FGF401 single agent phase II Group 1 (HCC, Asians) and Group 2 (HCC, non-Asians) and FGF401 in combination with PDR001 Phase II part [ Time Frame: 5 years ]
  4. Disease Control Rate (DCR)- phase I and phase II parts [ Time Frame: 5 years ]
  5. Time to Progression (TTP)- phase I part (at Maximum Tolerated Dose or Recommended Phase II Dose) and FGF401 in combination with PDR001 Phase II part [ Time Frame: 5 years ]
  6. Overall Survival (OS)- phase I (at Maximum Tolerated Dose or Recommended Phase II Dose) 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 (non-HCC, other solid tumors) and FGF401 in combination with PDR001 Phase II part [ Time Frame: 5 years ]
  8. Plasma concentration of FGF401 [ Time Frame: During phase I & II parts: Cycle 1 Day 8 (each cycle is 21 days) ]
  9. Concentration of PDR001 [ Time Frame: For FGF401 in combination with PDR001: Cycle 1 (each cycle is 21 days) ]
  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: Cycle 1 Day 1 (each cycle is 21 days) ]
  12. AUClast of PDR001 [ Time Frame: For FGF401 in combination with PDR001 phase I part: Cycle 1 Day 1 (each cycle is 21 days) ]
  13. AUCtau of PDR001 [ Time Frame: For FGF401 in combination with PDR001 phase I part: Cycle 1 Day 1 (each cycle is 21 days) ]
  14. T1/2 of PDR001 [ Time Frame: For FGF401 in combination with PDR001 phase I part: Cycle 1 Day 1 (each cycle is 21 days) ]
  15. Cmax of FGF401 [ Time Frame: During phase I part: Cycle 1 Day 1 & Day 8, Cycle 2 Day 1 (each cycle is 21 days) ]
  16. AUCinf of FGF401 [ Time Frame: During phase I part: Cycle 1 Day 1 & Day 8, Cycle 2 Day 1 (each cycle is 21 days) ]
  17. AUClast of FGF401 [ Time Frame: During phase I part: Cycle 1 Day 1 & Day 8, Cycle 2 Day 1 (each cycle is 21 days) ]
  18. AUCtau of FGF401 [ Time Frame: During phase I part: Cycle 1 Day 1 & Day 8, Cycle 2 Day 1 (each cycle is 21 days) ]
  19. T1/2 of FGF401 [ Time Frame: During phase I part: Cycle 1 Day 1 & Day 8, Cycle 2 Day 1 (each cycle is 21 days) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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.


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


Locations
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United States, California
Novartis Investigative Site
Los Angeles, California, United States, 90095
United States, Massachusetts
Novartis Investigative Site
Boston, Massachusetts, United States, 02114
United States, Texas
Novartis Investigative Site
Houston, Texas, United States, 77030
China, Jiangsu
Novartis Investigative Site
Nanjing, Jiangsu, China, 210002
China, Shanghai
Novartis Investigative Site
Shanghai, Shanghai, China, 200032
France
Novartis Investigative Site
Rennes Cedex, Ille Et Vilaine, France, 35062
Novartis Investigative Site
Lille Cedex, France, 59037
Novartis Investigative Site
Montpellier cedex 5, France, 34295
Novartis Investigative Site
Pessac Cedex, France, 33604
Novartis Investigative Site
Toulouse Cedex 9, France, 31059
Germany
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Hannover, Germany, 30625
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Wuerzburg, Germany, 97080
Hong Kong
Novartis Investigative Site
Hong Kong, Hong Kong
Italy
Novartis Investigative Site
Milano, MI, Italy, 20132
Novartis Investigative Site
Modena, MO, Italy, 41124
Japan
Novartis Investigative Site
Sayama, Osaka, Japan, 589 8511
Novartis Investigative Site
Chuo ku, Tokyo, Japan, 104 0045
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 05505
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 06351
Novartis Investigative Site
Seoul, Korea, Republic of, 03080
Singapore
Novartis Investigative Site
Singapore, Singapore, 169610
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site
Madrid, Spain, 28034
Taiwan
Novartis Investigative Site
Tainan, Taiwan ROC, Taiwan, 70403
Novartis Investigative Site
Taipei, Taiwan, 10002
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02325739    
Other Study ID Numbers: CFGF401X2101
First Posted: December 25, 2014    Key Record Dates
Last Update Posted: January 10, 2020
Last Verified: January 2020
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


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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