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 - Full Text View

Purpose

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.

Condition	Intervention	Phase
Solid Tumors and Advanced Endometrial Cancer Endometrial Cancer Second-line Treatment VEGF	Drug: TKI258	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Progression Free Survival (PFS) Rate [ Time Frame: up to 18 weeks ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Overall Response Rate (ORR) [ Time Frame: Baseline and every 6 weeks until disease progression, up to 18 weeks ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
Adverse event monitoring was conducted throughout the study.


Enrollment:	53
Study Start Date:	November 2011
Study Completion Date:	March 2014
Primary Completion Date:	March 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: TKI258 1 treatment arm (single agent TKI258), with patients classified into 2 groups based on their FGFR2 mutation status	Drug: TKI258 Other Name: dovitinib

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01379534

Show 45 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):

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.


Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01379534 History of Changes
Other Study ID Numbers:	CTKI258A2211 2011-000266-35
Study First Received:	June 6, 2011
Results First Received:	March 18, 2015
Last Updated:	May 2, 2015
Health Authority:	United States: Food and Drug Administration Canada: Health Canada Belgium: Federal Agency for Medicines and Health Products, FAMHP Germany: Federal Institutes for Drugs and Medical Devices (BfArM) Netherlands: Medicines Evaluation Board Singapore: Health Science Authority Italy: Italian Medicines Agency (AIFA)

Keywords provided by Novartis:


Solid tumors, advanced endometrial cancer, Endometrial Cancer, Second-line treatment, VEGF, Neoplasms, Endometrial Neoplasms, Uterine Neoplasms, Female Genital Neoplasms, Cancer, Carcinoma, Uterine Diseases,	Female Genital Diseases, Tumors, Oral Administration, Capsules, Tablets, CHIR258, CHIR-258, CHIR 258, TKI258, TKI-258, TKI 258

Additional relevant MeSH terms:


Endometrial Neoplasms Uterine Neoplasms Genital Neoplasms, Female Urogenital Neoplasms	Neoplasms by Site Neoplasms Uterine Diseases Genital Diseases, Female

ClinicalTrials.gov processed this record on September 26, 2016