A Phase II Study to Evaluate the Efficacy of TKI258 for the Treatment of Patients With FGFR2 Mutated or Wild-type Advanced and/or Metastatic Endometrial Cancer

• ClinicalTrials.gov Identifier: NCT01379534
• Recruitment Status: Completed
• First Posted: June 23, 2011
• Results First Posted: March 31, 2015
• Last Update Posted: May 20, 2015
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: June 6, 2011
• First Posted Date: June 23, 2011
• Results First Submitted Date: March 18, 2015
• Results First Posted Date: March 31, 2015
• Last Update Posted Date: May 20, 2015
• Study Start Date: November 2011
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 2, 2015)

Progression Free Survival (PFS) Rate [ Time Frame: up to 18 weeks ]

The 18-week PFS was defined as the percentage of participants who did not have a progression event at week 18. Participants who progressed, died, had response assessment of unknown (UNK) or discontinued before 18 weeks of observation without progression were counted as "failure". Progressive disease was assessed as per investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Original Primary Outcome Measures (submitted: June 22, 2011)

the antitumor activity of TKI258, as measured by an 18-week progression free survival rate [ Time Frame: up to 18 weeks after the first dose of study drug ]

The 18-week PFS is defined as the percentage of patients who do not have a progression event at week 18

Current Secondary Outcome Measures (submitted: March 18, 2015)

• Overall Response Rate (ORR) [ Time Frame: Baseline and every 6 weeks until disease progression, up to 18 weeks ]
  ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR).
• Disease Control Rate (DCR) [ Time Frame: Baseline and every 6 weeks until disease progression, up to 18 weeks ]
  DCR was defined as the percentage of participants with a best overall response of CR or PR or stable disease (SD).
• Duration of Response (DR) [ Time Frame: up to 18 weeks ]
  Duration of response was defined for participants with a CR or PR as the time from the date of the first documented response (CR or PR) to the date of the first documented progression or death due to disease. If a participants did not have a progression event, duration of response was censored at the date of the last adequate tumor assessment before the data analysis cut-off date or the antineoplastic therapy start date or the death date.
• Overall Survival (OS) [ Time Frame: up to 18 weeks ]
  OS was defined as the time from date of treatment to the date of death from any cause. If a participant was not known to have died at the date of analysis cut-off, the OS was censored at the last date of contact.
• Progression Free Survival (PFS) [ Time Frame: up to 18 weeks ]
  PFS was defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. If a participant did not have an event, PFS was censored at the date of last adequate response assessment before the data analysis cut-off date or the start date of new antineoplastic therapy after study drug discontinuation.
• Number of Participants With Adverse Events, Serious Adverse Events and Deaths [ Time Frame: up to 30 days after the last dose of study drug, up to 18 weeks ]
  Adverse event monitoring was conducted throughout the study.

Original Secondary Outcome Measures (submitted: June 22, 2011)

• Overall Response Rate (ORR) [ Time Frame: baseline and every 6 weeks until disease progression ]
  ORR is defined as percentage of patients with a best overall response of complete response (CR), partial response (PR) or progressive disease (PD)
• Disease Control Rate (DCR) [ Time Frame: baseline and every 6 weeks until disease progression ]
  DCR is defined as percentage of patients with a best overall response of CR, PR or stable disease (SD)
• characterize the safety and tolerability of TKI258 [ Time Frame: up to 30 days after the last dose of study drug ]
  Safety will be measured in terms of incidence of adverse events, serious adverse events, changes from baseline in vital signs, laboratory test results, ECG and cardiac imaging

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase II Study to Evaluate the Efficacy of TKI258 for the Treatment of Patients With FGFR2 Mutated or Wild-type Advanced and/or Metastatic Endometrial Cancer
• Official Title: A Phase II, Open-label, Single-arm, Non-randomized, Multi-center Study to Evaluate the Efficacy of Oral TKI258 as Second-line Therapy in Patients With Either FGFR2 Mutated or Wild-type Advanced and/or Metastatic Endometrial Cancer
• Brief Summary: This is a prospective, multi-center, open-label, single-arm, non-randomized, Phase II study to evaluate the efficacy and safety of TKI258 as second-line therapy in patients with either FGFR2 mutated or wild-type advanced and/or metastatic endometrial cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Solid Tumors and Advanced Endometrial Cancer
• Endometrial Cancer
• Second-line Treatment
• VEGF

Intervention

Drug: TKI258

Other Name: dovitinib

Study Arms

Experimental: TKI258

1 treatment arm (single agent TKI258), with patients classified into 2 groups based on their FGFR2 mutation status

Intervention: Drug: TKI258

• Publications *: Konecny GE, Finkler N, Garcia AA, Lorusso D, Lee PS, Rocconi RP, Fong PC, Squires M, Mishra K, Upalawanna A, Wang Y, Kristeleit R. Second-line dovitinib (TKI258) in patients with FGFR2-mutated or FGFR2-non-mutated advanced or metastatic endometrial cancer: a non-randomised, open-label, two-group, two-stage, phase 2 study. Lancet Oncol. 2015 Jun;16(6):686-94. doi: 10.1016/S1470-2045(15)70159-2. Epub 2015 May 13.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 24, 2014): 53
• Original Estimated Enrollment (submitted: June 22, 2011): 80
• Actual Study Completion Date: March 2014
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients with histologically confirmed diagnosis of advanced and/or metastatic endometrial cancer with available tissue specimen (either archival tissue or fixed fresh biopsy)
• Female patients ≥ 18 years old
• Documented radiologically confirmed progression of disease after prior first-line treatment evidence of progressive disease
• ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2
• At least one measurable lesion as per RECIST

Exclusion Criteria:

• Previous treatment with an FGFR inhibitor
• More than one line of treatment for advanced or metastatic disease
• Patients with uterine sarcomas, adenosarcoma, and malignant Mullerian tumors
• Patients with isolated recurrences (vaginal, pelvic, or para-aortic) potentially curative with radiation therapy or surgery
• Known central nervous system (CNS) metastases
• Malignancy within 3 years of study enrollment Other protocol-defined inclusion/exclusion criteria may apply

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil, Italy, Korea, Republic of, New Zealand, Spain, United Kingdom, United States
• Removed Location Countries: Egypt

Administrative Information

• NCT Number: NCT01379534
• Other Study ID Numbers: CTKI258A2211; 2011-000266-35 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Study Sponsor: Novartis Pharmaceuticals
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: May 2015