Urothelial CarcinomaPhase 2NCT02535650
Study of Tipifarnib in Patients With Previously-Treated, Advanced, HRAS Mutant Urothelial Carcinoma
A Phase 2 study testing tipifarnib in people with Urothelial Carcinoma, run by Samsung Medical Center at 1 site in South Korea.
Trial summary
Platinum-based chemotherapy is now regarded a standard first-line treatment for patients with advanced urothelial carcinoma (UC). However, patients who failed to response or experienced progression after platinum-based chemotherapy have a grim prognosis and a standard salvage treatment is not available. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Urothelial Carcinoma
- What is being tested?
- tipifarnib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteSouth Korea
- Study dates
- 12 Nov 2015to Jun 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is at least 20 years of age.
- Subject has a histologically or cytologically confirmed diagnosis of urothelial carcinoma arising from urinary bladder or upper urinary tract.
- Subject has been treated with platinum-based chemotherapy for advanced disease. They must have refractory or progressive disease for which there is no further curative therapy available.
- Subject has been treated with platinum-based chemotherapy for advanced disease. They must have refractory or progressive disease for which there is no further curative therapy available.
- Subject has a tumor that carries a missense HRAS mutation according to a standard methodology using Illumina HiSeqTM. (missence non-synonymous HRAS mutation and/or STK11: rs2075606 (T>C))HRAS status may have been assessed either in primary tumor tissue, recurrent or metastatic disease.
- Subject has consented to provide at least 10 unstained tumor slides for retrospective testing of HRAS gene tumor status.
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- Must have a life expectancy of 3 months or more
- Subject has measurable disease according to RECIST(Response Evaluation Criteria in Solid Tumors ) v1.1 and has relapsed (progressive disease) or is refractory to prior therapy.
- At least 2 weeks since the last systemic therapy regimen prior to enrolment. Subjects must have recovered to NCI CTCAE v. 4.03 < Grade 2 from all acute toxicities (excluding Grade 2 toxicities that are not considered a safety risk by the Sponsor and Investigator) or toxicity must be deemed irreversible by the Investigator.
- At least 2 weeks since last radiotherapy if radiation was localized to the only site of measurable disease, unless there is documentation of disease progression of the irradiated site. Patients must have recovered from all acute toxicities from radiotherapy.
- ECOG(Eastern Cooperative Oncology Group ) performance status of 0 or 1.
- Acceptable liver function:
- Bilirubin ≤ 1.5 times upper limit of normal (x ULN); does not apply to subjects with Gilbert's syndrome diagnosed as per institutional guidelines.
- AST (SGOT,aspartate aminotransferase ) and ALT (SGPT,Alanine aminotransferase) ≤ 3 x ULN; if liver metastases are present, then ≤ 5 x ULN is allowed.
- Acceptable renal function with serum creatinine ≤ 1.5 x ULN or a calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault or MDRD(Modification of Diet in Renal Disease ) formulas. Serum potassium with normal or ≤ CTCAE Grade 1 with or without supplementation.
- Acceptable hematologic status (without growth factor support or transfusion dependency):
- ANC(absolute neutrophil count )>1500 cells/μL.
- Platelet count >100,000/μL.
- Hemoglobin >9.0 g/dL.
- Female subjects must be either:
- Of non-child-bearing potential (surgically sterilized or at least 2 years post-menopausal); or
- If of child-bearing potential, subject must use an adequate method of contraception consisting of two-barrier method or one barrier method with a spermicide or intrauterine device. Both females and male subjects with female partners of child-bearing potential must agree to use an adequate method of contraception for 2 weeks prior to screening, during, and at least 4 weeks after last dose of trial medication. Female subjects must have a negative serum or urine pregnancy test within 72 hours prior to start of trial medication.
- Not breast feeding at any time during the study.
- Written and voluntary informed consent understood, signed and dated.
Who cannot join
- Ongoing treatment with an anticancer agent not contemplated in this protocol.
- Prior treatment (at least 1 full treatment cycle) with an FTase inhibitor.
- Any history of clinically relevant coronary artery disease or myocardial infarction within the last 3 years, New York Heart Association (NYHA) grade III or greater congestive heart failure, cerebrovascular attack within the prior year, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
- Known uncontrolled brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 4 weeks prior to Cycle 1 Day 1). Subjects that develop brain metastasis during the study may have their treatment interrupted to receive a course of cranial radiation and restart trial medication after a recovery period of at least 1 week. High dose corticosteroids may be employed for the management of cranial radiation but must be tapered off before resuming treatment.
- Non-tolerable > Grade 2 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
- Major surgery, other than diagnostic surgery, within 4 weeks prior to Cycle 1 Day 1, without complete recovery.
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- Double primary cancer of other site(s), except for cured ones at the discretion of investigator
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy. Known infection with HIV, or an active infection with hepatitis B or hepatitis C.
- Subjects who have exhibited allergic reactions to tipifarnib, structural compounds similar to tipifarnib or to its excipients.
- Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this study.
- The subject has legal incapacity or limited legal capacity.
- Dementia or significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol. Unwillingness or inability to comply with the study protocol for any reason.
- QTcF interval ≥ 470 msecs
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open Label Phase II Study of Tipifarnib in Patients With Previously-Treated, Advanced, HRAS Mutant Urothelial Carcinoma
Platinum-based chemotherapy is now regarded a standard first-line treatment for patients with advanced urothelial carcinoma (UC). However, patients who failed to response or experienced progression after platinum-based chemotherapy have a grim prognosis and a standard salvage treatment is not available.
UC is known to harbor multiple mutations. In the investigators' own high-throughput molecular profiling study, the most commonly observed mutations included TP53, FGFR3(fibroblast growth factor receptor 3 ) and HRAS. Since RAS signaling can be attenuated using selective farnesyl transferase (FTase) inhibitors, tipifarnib, a highly potent and selective inhibitor of FTase, was proposed to be an effective therapeutic approach in the treatment of UC.
- Conditions
- Urothelial Carcinoma
- Being tested
- tipifarnib
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tipifarnibDrug
Tipifarnib will be administered at a starting dose of 900 mg, po, bid on days 1-7 and 15-21 of 28-day treatment cycles. In the absence of unmanageable toxicities, subjects may continue to receive tipifarnib treatment for up to 12 months as long as the Investigator considers that the treatment is providing clinical benefit.
| Study group | Role | What they receive |
|---|---|---|
| tipifarnib | Experimental | Tipifarnib will be administered at a starting dose of 900 mg, po, bid on days 1-7 and 15-21 of 28-day treatment cycles. Receives: Drug: tipifarnib |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-month progression-free survival
Measured: Up to 6 months for each subject
Secondary outcomes (3)
Duration of response
Measured: Up to 12 months for each subject
Overall survival
Measured: Until the date of death from any cause, whichever came first, assessed up to 1 year 6 months.
Safety and Tolerability
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0(Common Toxicity Criteria for Adverse Effects )
Measured: Up to 12 months for each subject
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2015 (estimated)
- Study start12 Nov 2015
- Primary completionMar 2022 (estimated)
- Study completionJun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by Samsung Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Park, Se-Hoon, Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02535650
- Sponsor's protocol ID
- 2015-05-039
- Status last verified
- Mar 2022
- First submitted
- 25 Aug 2015
- Last updated
- 8 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Phase II Study of Tipifarnib in Patients With Previously-Treated, Advanced, HRAS Mutant Urothelial Carcinoma
- ClinicalTrials.gov ID
- NCT02535650
- Acronym / sponsor ID
- 2015-05-039
- Conditions
- Urothelial Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Study start
- 12 Nov 2015 (actual)
- Primary completion
- Mar 2022 (estimated)
- Study completion
- Jun 2022 (estimated)
- First posted
- 28 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Platinum-based chemotherapy is now regarded a standard first-line treatment for patients with advanced urothelial carcinoma (UC). However, patients who failed to response or experienced progression after platinum-based chemotherapy have a grim prognosis and a standard salvage treatment is not available.
UC is known to harbor multiple mutations. In the investigators' own high-throughput molecular profiling study, the most commonly observed mutations included TP53, FGFR3(fibroblast growth factor receptor 3 ) and HRAS. Since RAS signaling can be attenuated using selective farnesyl transferase (FTase) inhibitors, tipifarnib, a highly potent and selective inhibitor of FTase, was proposed to be an effective therapeutic approach in the treatment of UC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| tipifarnib | Experimental | Drug: tipifarnibTipifarnib will be administered at a starting dose of 900 mg, po, bid on days 1-7 and 15-21 of 28-day treatment cycles. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Subject is at least 20 years of age.
- Subject has a histologically or cytologically confirmed diagnosis of urothelial carcinoma arising from urinary bladder or upper urinary tract.
- Subject has been treated with platinum-based chemotherapy for advanced disease. They must have refractory or progressive disease for which there is no further curative therapy available.
- Subject has been treated with platinum-based chemotherapy for advanced disease. They must have refractory or progressive disease for which there is no further curative therapy available.
- Subject has a tumor that carries a missense HRAS mutation according to a standard methodology using Illumina HiSeqTM. (missence non-synonymous HRAS mutation and/or STK11: rs2075606 (T>C))HRAS status may have been assessed either in primary tumor tissue, recurrent or metastatic disease.
Key exclusion criteria (13 listed)
- Ongoing treatment with an anticancer agent not contemplated in this protocol.
- Prior treatment (at least 1 full treatment cycle) with an FTase inhibitor.
- Any history of clinically relevant coronary artery disease or myocardial infarction within the last 3 years, New York Heart Association (NYHA) grade III or greater congestive heart failure, cerebrovascular attack within the prior year, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
- Known uncontrolled brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 4 weeks prior to Cycle 1 Day 1). Subjects that develop brain metastasis during the study may have their treatment interrupted to receive a course of cranial radiation and restart trial medication after a recovery period of at least 1 week. High dose corticosteroids may be employed for the management of cranial radiation but must be tapered off before resuming treatment.
- Non-tolerable > Grade 2 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tipifarnibTipifarnib will be administered at a starting dose of 900 mg, po, bid on days 1-7 and 15-21 of 28-day treatment cycles. In the absence of unmanageable toxicities, subjects may continue to receive tipifarnib treatment for up to 12 months as long as the Investigator considers that the treatment is providing clinical benefit. | Drug | tipifarnib |
Primary outcome
6-month progression-free survival
Time frame: Up to 6 months for each subject
3 secondary outcomes
Duration of response
Time frame: Up to 12 months for each subject
Overall survival
Time frame: Until the date of death from any cause, whichever came first, assessed up to 1 year 6 months.
Safety and Tolerability
Time frame: Up to 12 months for each subject
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing tipifarnib in people with Urothelial Carcinoma, run by Samsung Medical Center at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6-month progression-free survival (time frame: Up to 6 months for each subject). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2022.