Biomarkers in Urothelial Cancer Patients Treated With Pembrolizumab

NCT03263039 | Unknown Phase 2

• 1 other identifier: NL61719.056.17
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

In the RESPONDER study, the role of the immune evasive mechanisms combined with genomic characterization will be explored in urothelial cancer patients treated with second-line treatment with pembrolizumab. Combined profiling of immune and molecular status is novel and may contribute to improved patient stratification and provide rationale for future treatment strategies containing pembrolizumab.

Conditions

Transitional Cell Carcinoma of the Bladder; Biomarkers

Keywords

Programmed Cell Death 1 Receptor; Pembrolizumab; Keytruda; MK-3475; Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Biomarkers in patients with clinical benefit

  Peripheral blood and sequential tumor biopsies are collected before start of treatment, during treatment, and (optionally) at progression. Immune profiling using in situ multiplex immunofluorescence will be performed to identify tumor epithelial and stromal cells, effector immune cells, T cell co-inhibition, T cell recruitment and immune-suppressive cells. Furthermore, serum samples will be assessed for levels of cytokines/chemoattractants. Finally, longitudinal blood samples will be collected for isolation of immune cells, cytokine/chemo-attractants and ctDNA. A qualified pathologist will determine tumor cell percentage in the obtained biopsies. DNA will be obtained from both cancer cells (biopsy tissue) and normal white blood cells (peripheral blood) and will be submitted for whole genome sequencing. The obtained data will contribute to identifying potential biomarkers in patients with clinical benefit.

  End of study (pembrolizumab will be given for a maximum of 24 months), which is within 3 years after start of inclusion

Secondary Outcomes (2)

• Mechanisms of primary and acquired resistance to pembrolizumab

  End of study (pembrolizumab will be given for a maximum of 24 months), which is anticipated to be within 3 years after start inclusion.

• Correlations between biomarkers and clinical activity

  End of study (pembrolizumab will be given for a maximum of 24 months), which is anticipated to be within 3 years after start inclusion.

Other Outcomes (1)

• Translation experiments

  Collection of samples will be until end of study (pembrolizumab will be given for a maximum of 24 months), which is anticipated to be within 3 years after start inclusion.

Study Arms (1)

Treatment with pembrolizumab

OTHER

Pembrolizumab will be administered at a flat dose of 200 mg as a 30 minute (-5 min/+10 min) IV infusion every 3 weeks (Q3W)

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Pembrolizumab 200 mg Q3W

Also known as: MK-3475, Keytruda

Treatment with pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Should have signed informed consent for CPCT-02 (this is another clinical trial, NCT01855477)
• Be willing and able to provide written informed consent for the trial.
• Be \>= 18 years of age on day of signing informed consent.
• Have histologically or cytologically-confirmed urothelial cancer that is not amenable to curative treatment with local and/or systemic therapies.
• 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
• 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.
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. 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.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Demonstrate adequate organ function according to screening labs, which should be performed within 10 days of treatment initiation.
• 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. lf the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in protocol - Contraception, for the course of the study through 120 days after the last dose of study medication.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in protocol- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

You may not qualify if:

• Treatment with an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• 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.
• Has a known history of active TB (Tuberculosis Bacillus).
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., :S 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., :S 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Erasmus MC

Rotterdam, Netherlands

Location

Related Publications (1)

• Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.

  PMID: 32203306 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• M.P.J.K. Lolkema

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

• A.A.M. van der Veldt

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 18, 2017
• First Posted: August 28, 2017
• Study Start: August 21, 2017
• Primary Completion: August 19, 2022
• Study Completion: August 19, 2023
• Last Updated: August 20, 2021

Record last verified: 2021-08

Locations

NL (1)