A clinical trial to study whether the daily oral drug ODM-203 (Inhibitor of FGFR and VEGF-Receptor) is safe and effective for bladder cancer patients
- Conditions
- Health Condition 1: C679- Malignant neoplasm of bladder, unspecified
- Registration Number
- CTRI/2021/11/038092
- Lead Sponsor
- Aurigene Discovery Technologies Limited Subsidiary of Dr Reddys Laboratories Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
1.Males and females >= 18 years of age
2.Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.
3.Patients with histologically confirmed Unresectable Urothelial Transitional Cell Carcinoma
4.Patient should have received at least 1 line and a maximum of 2 prior lines of systemic therapy (Patients who have received chemotherapy in an adjuvant or neoadjuvant setting are also eligible as long as the tumor has relapsed during or within 12 months of having completed the adjuvant / neoadjuvant therapy)
5.Patient consents for pre-screening for FGFR3 mutation testing on available archival or fresh tissue sample.
6.Positive for FGFR3 mutation (fusion and/or non-fusion mutation)
7.Patient consents for germline testing for UGT1A1 polymorphism.
8.Patients with homozygous wild type (wt/wt) genotype or heterozygous wild type allele
9.Evidence of measurable disease per RECIST, v1.1.
10.Acceptable bone marrow function, organ function and serum electrolytes at screening as described below:
a.Absolute neutrophil count (ANC) >= 1.5 x 109/L (1500 per mm3) (without WBC growth factor support)
b.Platelet count >= 90 x 109/L (90,000 per mm3) without platelet transfusion support
c.Hemoglobin (Hb) >= 9.0 g/dL (Blood could be transfused during screening period, to bring Hb to this level)
d.Total Bilirubin <= 1.2 x ULN
e.AST (SGOT) <= 1.5 x ULN [<= 3 Ã? ULN if known liver metastases or the tumor invades the liver]
f.ALT (SGPT) <= 1.5 x ULN [<= 3 Ã? ULN if known liver metastases or the tumor invades the liver]
g.Serum creatinine <= 2 mg/dL or a measured creatinine clearance >= 40 mL/min according to Cockcroft-Gault formula.
h.Serum Phosphate, Calcium, Potassium and Sodium in normal range or <= Grade 1 increase / decrease
11.Ability to swallow and retain oral medications.
12.Negative serum pregnancy test in women of childbearing potential (WOCBP)
13.Women of childbearing potential and men who partner with such a woman of childbearing potential must agree to use one or more of highly effective method(s) for contraception, as detailed in section 7.18 of the protocol, for the duration of the study, i.e., through 28-day safety follow up visit.
14.Willing and able to provide written informed consent and comply with the requirements of the trial
1. Patients without FGFR3 mutation
2. Patients without any wild type allele genotypes for UGT1A1
3. Systemic anti-cancer therapy, such as chemotherapy, or immunotherapy received within the past 28 days or 5 half-lives of Cycle 1 Day 1, whichever is longer.
4. Radiotherapy within the previous 14 days of Cycle 1 day 1
5. Patients who have received an approved or investigational FGFR inhibitor in the past.
6. Use of any investigational agent within 28 days or 5 half-lives prior to Cycle 1 day 1.
7. Presence of an acute or chronic toxicity resulting from prior systemic therapy, such as chemotherapy
8. CNS metastases
9. Major surgery less than 21 days from the start of treatment
10. Current active infection requiring systemic therapy.
11. Known to be positive for HIV or AIDS or hepatitis B or hepatitis C or Identified during Screening
12. >= Grade 2 retinopathy and/or >= Grade 2 keratitis at screening ophthalmic examination
13. Any severe, acute, or chronic medical, psychiatric or social condition or laboratory abnormality
14. Previous or concomitant additional malignancy within the last 5 years prior to study entry
15. Pregnant or lactating women
16. CHF, MI, Angina, Pulmonary embolism within 3 months prior to initiation of study drug.
17. Left Ventricular Ejection Fraction (LVEF) < 50 percent at screening.
18. Left Ventricular Ejection Fraction (LVEF) < 50 percent at screening.
19. Gastrointestinal disease or disorders that may interfere with the tolerance or absorption of orally- administered drugs.
20. Previous or concomitant additional malignancy within the last 5 years prior to study entry
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) by RECIST 1.1Timepoint: Through cycle 6
- Secondary Outcome Measures
Name Time Method Clinical Benefit RateTimepoint: at Cycle 4 and 6;Complete Response (CR) and Partial Response (PR) rates by RECIST 1.1Timepoint: End of Treatment Visit;Duration of Response (DoR), Time to response, Time to Progression, Progression Free Survival (PFS) and Overall Survival (OS), Duration of CBRTimepoint: End of Treatment Visit;Overall Response Rate (ORR) by RECIST 1.1Timepoint: End of Treatment Visit;Pharmacokinetic measurements in plasma and urine (Urine measurements are optional)Timepoint: on Cycle 1 Days 1, 2, 8, 15 and 16 (9-time points on day1 and 15 and 1 time-point pre-dose on day 8; the last time point on day 1 and day 15 will correspond to 24 hours from the previous dose;Safety profile as measured by AEs / SAEs / laboratory parametersTimepoint: throughout study;Stable Disease (SD)Timepoint: after Cycle 4, Cycle 6, and Cycle 8