Biomarker discovery study to identify patients with advanced urothelial cancer benefitting from pembrolizumab treatment

Phase 1

• Conditions: advanced urothelial cancer; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-000976-27-NL
• Lead Sponsor: Erasmus MC Cancer Institute

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-07-12
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 80

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria:
1.Should have signed informed consent for CPCT-02.
Note: when a safe biopsy of a metastatic or locally advanced lesion is not deemed possible by the treating investigator, subject may be included in the trial without participation in the CPCT-02 trial only upon approval by the central principal investigator.
2.Be willing and able to provide written informed consent for the trial.
3.Be ? 18 years of age on day of signing informed consent.
4.Have histologically or cytologically-confirmed urothelial cancer that is not
amenable to curative treatment with local and/or systemic therapies.
5.Second-line treatment: have progressive disease after platinum containing chemotherapy as defined by:
-Disease progression after treatment with a platinum-containing regimen for recurrent (disease not amenable to curative treatment)/metastatic disease
-Recurrence/progression within 12 months of prior therapy containing platinum
OR
First-line treatment: have received no prior systemic chemotherapy for advanced/unresectable (inoperable) or metastatic urothelial
a.Adjuvant platinum based chemotherapy, following radial cystectomy, with recurrence > 12 months from completion of therapy is permitted
b.Neoadjuvant platinum based chemotherapy, with recurrence > 12 months since completion of therapy is permitted.
Note: Low-dose chemotherapy (e.g., low dose cisplatin, cisplatin+5FU, mytomycin+5FU, or cisplatin+paclitaxel) given concurrent with radiation to the primary tumor site is not considered as systemic therapy.
And subject must be considered ineligible to receive cisplatin-based combination therapy, based on having at least one of the following criteria:
a.Creatinine clearance (calculated or measured) < 60 mL/min but >30 mL/min
Note: Subjects with a creatinine clearance (calculated or measured) < 30 mL/min or on dialysis are excluded from the trial.
b.CTCAE v.4, Grade >2 audiometric hearing loss (25dB in two consecutive wave ranges)
c.CTCAE v.4, Grade >2 peripheral neuropathy
d.NYHA Class III heart failure (Appendix 13.1)
6.Cisplatin-unfit patients should have a PD-L1 CPS of ?10, determined with the use of the commercially available PD-L1 IHC 22C3 pharmDx assay on a DAKO stainer.
PD-L1 expression may be determined prior to enrollment or during the screening phase.
7.Have measurable disease based on RECIST 1.1. Tumor lesions located in a previously irradiated area are considered measurable if progression has been demonstrated in these lesions.
8.Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly
8.-Note: newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
-Note: when a safe biopsy of a metastatic or locally advanced lesion is n

Exclusion Criteria

1. Treamtent with an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
2. Has a diagnosis of immunodeficiency or is receiving high dose systemic steroid therapy (defined as > 20 mg prednisone or equivalent per day) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
3. Has a known history of active TB (Bacillus Tuberculosis).
4. Hypersensitivity to pembrolizumab or any of its excipients.
5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
6. 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., = Grade 1 or at baseline) from adverse events due to a previously administered agent.
- Note: Subjects with = 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.
- Note: Radiation therapy to a symptomatic solitary lesion or to the brain may be allowed at the investigator’s discretion
7. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or
squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
Diagnosis of prostate carcinoma in cystectomy material is not an exclusion criterium.
8. 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 high dose steroids (defined as > 20 mg prednisone or equivalent per day) for at least 7 days prior to trial treatment. This
exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
9. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents,
corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
10. Has known history of, or any evidence of active, (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis.
11. Has an active infection requiring systemic therapy.
12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the sub

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified