Endometrial Cancer, Second-line Treatment, Solid Tumors and Advanced Endometrial Cancer, VEGF
Conditions
Keywords
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
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.
Interventions
DRUGTKI258
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | 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) | 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 Response Rate (ORR) | 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). |
| Progression Free Survival (PFS) | 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 | up to 30 days after the last dose of study drug, up to 18 weeks | Adverse event monitoring was conducted throughout the study. |
| Overall Survival (OS) | 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. |
Countries
Brazil, Italy, New Zealand, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were treated with TKI258 until disease progression, unacceptable toxicity, death or discontinuation due to any other reason. All participants were followed for at least 30 days after their last dose of study drug for safety assessment.
Pre-assignment details
If a participant didn't discontinue study drug due to disease progression, death, lost to follow-up or withdrawn consent to post treatment tumor assessment, then tumor assessments continued every 6 weeks until the start of new anti-cancer therapy, disease progression, death, lost to follow-up or withdrawn consent to tumor status follow-up.
Participants by arm
| Arm | Count |
|---|---|
| FGFR2 (MUT) Participants were classified into two groups based on mutational status of FGFR2 and all participants were treated with 500 mg of TKI258on a 5 day on / 2 days off dosing regimen for 13 weeks. | 22 |
| FGFR2 (WT) Participants were classified into two groups based on mutational status of FGFR2 and all participants were treated with 500 mg of TKI258on a 5 day on / 2 days off dosing regimen for 13 weeks. | 31 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Phase | Adverse Event | 7 | 7 |
| Treatment Phase | Progressive disease | 13 | 22 |
| Treatment Phase | Withdrawal by Subject | 2 | 2 |
| Tumor Assessment Follow-up (f/u) Phase | Adverse Event | 1 | 0 |
| Tumor Assessment Follow-up (f/u) Phase | Death | 0 | 1 |
| Tumor Assessment Follow-up (f/u) Phase | Lost to Follow-up | 0 | 1 |
| Tumor Assessment Follow-up (f/u) Phase | Progressive disease | 3 | 0 |
Baseline characteristics
| Characteristic | FGFR2 (MUT) | FGFR2 (WT) | Total |
|---|---|---|---|
| Age, Continuous | 61.9 Years STANDARD_DEVIATION 10.54 | 64.4 Years STANDARD_DEVIATION 8.63 | 63.4 Years STANDARD_DEVIATION 9.45 |
| Sex/Gender, Customized | 22 Participants | 31 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 22 | 31 / 31 |
| serious Total, serious adverse events | 10 / 22 | 20 / 31 |
Outcome results
Primary
Progression Free Survival (PFS) Rate
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.
Time frame: up to 18 weeks
Population: Primary endpoint analysis set (PEAS): The PEAS included all participants who received at least one dose of study medication and had measurable disease at baseline as confirmed by a local Investigator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FGFR2 (MUT) | Progression Free Survival (PFS) Rate | 31.8 Percentage of participants |
| FGFR2 (WT) | Progression Free Survival (PFS) Rate | 29.0 Percentage of participants |
Secondary
Disease Control Rate (DCR)
DCR was defined as the percentage of participants with a best overall response of CR or PR or stable disease (SD).
Time frame: Baseline and every 6 weeks until disease progression, up to 18 weeks
Population: Primary endpoint analysis set (PEAS): The PEAS included all participants who received at least one dose of study medication and had measurable disease at baseline as confirmed by a local Investigator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FGFR2 (MUT) | Disease Control Rate (DCR) | 63.6 Percentage of participants |
| FGFR2 (WT) | Disease Control Rate (DCR) | 51.6 Percentage of participants |
Secondary
Duration of Response (DR)
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.
Time frame: up to 18 weeks
Population: This outcome measure was not analyzed. The analysis was not required because there were too few responders.
Secondary
Number of Participants With Adverse Events, Serious Adverse Events and Deaths
Adverse event monitoring was conducted throughout the study.
Time frame: up to 30 days after the last dose of study drug, up to 18 weeks
Population: Safety analysis set: The safety set included all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FGFR2 (MUT) | Number of Participants With Adverse Events, Serious Adverse Events and Deaths | Adverse events (serious and non-serious) | 22 Participants |
| FGFR2 (MUT) | Number of Participants With Adverse Events, Serious Adverse Events and Deaths | Serious adverse events | 10 Participants |
| FGFR2 (MUT) | Number of Participants With Adverse Events, Serious Adverse Events and Deaths | Deaths | 1 Participants |
| FGFR2 (WT) | Number of Participants With Adverse Events, Serious Adverse Events and Deaths | Adverse events (serious and non-serious) | 31 Participants |
| FGFR2 (WT) | Number of Participants With Adverse Events, Serious Adverse Events and Deaths | Serious adverse events | 20 Participants |
| FGFR2 (WT) | Number of Participants With Adverse Events, Serious Adverse Events and Deaths | Deaths | 4 Participants |
Secondary
Overall Response Rate (ORR)
ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR).
Time frame: Baseline and every 6 weeks until disease progression, up to 18 weeks
Population: Primary endpoint analysis set (PEAS): The PEAS included all participants who received at least one dose of study medication and had measurable disease at baseline as confirmed by a local Investigator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FGFR2 (MUT) | Overall Response Rate (ORR) | 4.5 Percentage of participants |
| FGFR2 (WT) | Overall Response Rate (ORR) | 16.1 Percentage of participants |
Secondary
Overall Survival (OS)
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.
Time frame: up to 18 weeks
Population: Full Analysis Set (FAS): The FAS included all participants who received at least one dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FGFR2 (MUT) | Overall Survival (OS) | 20.2 Months |
| FGFR2 (WT) | Overall Survival (OS) | 9.3 Months |
Secondary
Progression Free Survival (PFS)
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.
Time frame: up to 18 weeks
Population: Primary endpoint analysis set (PEAS): The PEAS included all participants who received at least one dose of study medication and had measurable disease at baseline as confirmed by a local Investigator.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FGFR2 (MUT) | Progression Free Survival (PFS) | 4.1 Months |
| FGFR2 (WT) | Progression Free Survival (PFS) | 2.7 Months |