Urothelial CancerPhase 1NCT02880345
RADVAX™: A Trial of Combined Pembrolizumab and Hypofractionated Radiation in Patients With Advanced Urothelial Cancer Who Have Progressed on Anti-PD-1/PD-L1 Monotherapy
A Phase 1 study testing PEMBROLIZUMAB and hypofractionated radiation in people with Urothelial Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
This is a pilot study of a fixed dose of Pembrolizumab in combination with two different regimens of hypofractionated radiation. It is designed to demonstrate the activity and safety of the combination treatment in advanced urothelial cancer patients with prior exposure to PD-1 inhibitors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Cancer
- What is being tested?
- PEMBROLIZUMAB and hypofractionated radiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2016to Dec 2018
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be willing and able to provide written informed consent/assent for the trial.
- Be 18 years of age or older on day of signing informed consent.
- Histologically confirmed diagnosis of pure or mixed urothelial cancer.
- Stage IV cancer by AJCC staging criteria. Patients who are stage IV as a result of cT4b disease only are not eligible.
- Progression of disease (radiographic or clinical) while on anti-PD-1 or anti-PD-L1 therapy at least 9 weeks or more from the date of starting anti-PD-1 or anti-PD-L1 therapy.
- Presence of an index lesion greater than or equal to 1 cm amenable to hypofractionated radiotherapy
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- Patients who have metastatic cancer must have at least one lesion that is outside the radiation field that measures greater than one cm that can be followed by RECIST 1.1. This lesion, if it is close to the radiated lesion, must receive no more than 10% of the dose prescribed to the target lesion.
- Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion.
- Have a performance status of 0 or 1 on the ECOG Performance Scale.
- Ability to tolerate hypofractionated radiation therapy (e.g. lie flat and hold position)
- Demonstrate adequate organ function, all screening labs should be performed within 14 days of treatment initiation.
- Patients on dialysis are excluded from this study.
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for more than 1 year. 14. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Who cannot join
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Systemic steroids administered specifically as a premedication for chemotherapy infusion or radiotherapy are allowed.
- Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., less than or at Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., less than or at Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: Subjects with less than or Grade 2 neuropathy are an exception to this criterion and may qualify for the study. - Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- A history of prior radiotherapy that precludes delivery of hypofractionated radiotherapy
- Has a known additional malignancy that is progressing or requires active treatment.
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- Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
- Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogrens syndrome will not be excluded from the study.
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subjects participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the prescreening or screening visit through 120 days after the last dose of trial treatment.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days prior to the first dose of trial treatment.
- Had progression of disease within 9 weeks of starting prior anti-PD-1 or anti-PD-L1 monotherapy therapy.
- Has not had prior cisplatinum-based chemotherapy, unless the subject is considered cisplatinum-ineligible based on meeting at least one of the following criteria: a. ECOG performance status of 2 (the proportion of ECOG 2 subjects will be limited to approximately 50% of the total population) b. Creatinine clearance (calculated or measured) less than 60 mL/min but greater than 30 mL/min Note: Subjects with a creatinine clearance (calculated or measured) less than 30 mL/min or on dialysis are excluded from the trial. c. CTCAE v.4, Greater than Grade 2 audiometric hearing loss (25dB in two consecutive wave ranges) d. CTCAE v.4, Greater than Grade 2 peripheral neuropathy e. NYHA Class III heart failure
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: RADVAX™: A Pilot Trial of Combined Pembrolizumab and Hypofractionated Radiation in Patients With Advanced Urothelial Cancer Who Have Progressed on Anti-PD-1/PD-L1 Monotherapy
This is a pilot study of a fixed dose of Pembrolizumab in combination with two different regimens of hypofractionated radiation. It is designed to demonstrate the activity and safety of the combination treatment in advanced urothelial cancer patients with prior exposure to PD-1 inhibitors.
- Conditions
- Urothelial Cancer
- Being tested
- PEMBROLIZUMAB, hypofractionated radiation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PEMBROLIZUMABDrug
hypofractionated radiationRadiation
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 - 8 Gy x 3 fractions | Active comparator | 8 Gy x 3 fractions Receives: Drug: PEMBROLIZUMAB; Radiation: hypofractionated radiation |
| Cohort 2 - 17 Gy x 1 fractions | Active comparator | 17 Gy x 1 fraction Receives: Drug: PEMBROLIZUMAB; Radiation: hypofractionated radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Adverse Events
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2016 (estimated)
- Study startAug 2016
- Primary completionAug 2017
- Study completionDec 2018
Why it stopped: Insufficient accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urothelial CancerStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John Christodouleous, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02880345
- Sponsor's protocol ID
- UPCC 22816
- Status last verified
- Apr 2019
- First submitted
- 19 Aug 2016
- Last updated
- 23 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RADVAX™: A Pilot Trial of Combined Pembrolizumab and Hypofractionated Radiation in Patients With Advanced Urothelial Cancer Who Have Progressed on Anti-PD-1/PD-L1 Monotherapy
- ClinicalTrials.gov ID
- NCT02880345
- Acronym / sponsor ID
- UPCC 22816
- Conditions
- Urothelial Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Insufficient accrual
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- Aug 2016 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 26 Aug 2016 (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.
This is a pilot study of a fixed dose of Pembrolizumab in combination with two different regimens of hypofractionated radiation. It is designed to demonstrate the activity and safety of the combination treatment in advanced urothelial cancer patients with prior exposure to PD-1 inhibitors.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 - 8 Gy x 3 fractions | Active comparator | Drug: PEMBROLIZUMAB, Radiation: hypofractionated radiation8 Gy x 3 fractions |
| Cohort 2 - 17 Gy x 1 fractions | Active comparator | Drug: PEMBROLIZUMAB, Radiation: hypofractionated radiation17 Gy x 1 fraction |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Be willing and able to provide written informed consent/assent for the trial.
- Be 18 years of age or older on day of signing informed consent.
- Histologically confirmed diagnosis of pure or mixed urothelial cancer.
- Stage IV cancer by AJCC staging criteria. Patients who are stage IV as a result of cT4b disease only are not eligible.
- Progression of disease (radiographic or clinical) while on anti-PD-1 or anti-PD-L1 therapy at least 9 weeks or more from the date of starting anti-PD-1 or anti-PD-L1 therapy.
Key exclusion criteria (19 listed)
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Systemic steroids administered specifically as a premedication for chemotherapy infusion or radiotherapy are allowed.
- Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., less than or at Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., less than or at Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: Subjects with less than or Grade 2 neuropathy are an exception to this criterion and may qualify for the study. - Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- A history of prior radiotherapy that precludes delivery of hypofractionated radiotherapy
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 |
|---|---|---|
| PEMBROLIZUMAB | Drug | Cohort 1 - 8 Gy x 3 fractions, Cohort 2 - 17 Gy x 1 fractions |
| hypofractionated radiation | Radiation | Cohort 1 - 8 Gy x 3 fractions, Cohort 2 - 17 Gy x 1 fractions |
Primary outcome
Number of Adverse Events
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2019.
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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.
John Christodouleous, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PEMBROLIZUMAB and hypofractionated radiation in people with Urothelial Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
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 14 inclusion and 19 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: withdrawn, as of the sponsor's last update on 23 Apr 2019. 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 United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Number of Adverse Events (time frame: 2 years). 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 23 Apr 2019.