Tab Title Description
Describes the nature of a clinical study. Types include:
- Observational study — observes people and measures outcomes without affecting results.
- Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
- Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
NCT ID: NCT04387461
Sponsor Protocol Number: CG2003C
About this study
The primary purpose of this study is to evaluate the activity of intravesical administration of CG0070 and intravenous administration of Pembrolizumab in patients with tissue pathology-confirmed non-muscular invasive bladder cancer (NMIBC) who have Bacillus-Calmette-Guerin (BCG) unresponsive disease with carcinoma in situ (CIS) with or without Ta/T1 papillary disease.
Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
- Be ≥ 18 years of age (or legal age of majority in the jurisdiction) on day of signing informed consent.
- Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Have pathologically confirmed (World Health Organization [WHO] grading system employed for tumor grading) (Compérat 2018) CIS unresponsive to prior BCG therapy. Patients with CIS unresponsive to BCG are those unlikely to benefit from and who will not be receiving further IVE BCG. There is no maximum limit to the amount of prior BCG past treatment but maintenance BCG should be administered on a schedule consistent with standard induction-maintenance protocols (e.g., BCG weekly x 6 then weekly x 3 weeks administered at Months 3, 6, 12, 18, 24, and 36). The definition of BCG unresponsive CIS will also require the following:
- Relapsed or persistent CIS (with or without HG Ta or T1 disease) within 12 months of the completion (last dose) of adequate BCG treatment;
- Pathological confirmation of BCG unresponsive CIS within 10 weeks of study enrollment;
- CIS specimen must be predominantly urothelial (transitional cell) and have less than 50% variant (e.g., sarcomatoid, squamous etc. component) histology;
- No maximum limit to the amount of BCG administered but maintenance BCG should be administered on a schedule consistent with the SWOG 8507 regimen (Lamm 2000);
- Any disease-free interval of 2 years or more from the last dose of adequate BCG must be assumed to be a new primary tumor with prior BCG treatments not counted towards qualification for the study.
- Have all Ta and/or T1 disease resected and all CIS resected or fulgurated, as feasible, prior to study treatment (e.g., prior to Day 1 treatment)
- NOTE: T1 disease resection site must have biopsy evaluation of the prior resection site 2–8 weeks prior to initial study treatment.
- Received prior adequate BCG therapy as defined as at least one of the following (“5+2” minimum exposure; all 7 qualifying doses must be greater than or equal to one third [1/3] of full dose BCG):
- At least 5 of 6 doses of an initial induction course (adequate induction) plus at least 2 of 3 doses of maintenance therapy; OR
- At least 5 of 6 doses of an initial induction course (adequate induction) plus at least 2 of 6 doses of a second induction course.
- NOTE: Past qualifying “adequate BCG” must be clearly documented including dates of BCG treatment and pathological recurrence or persistence within 12 months of last dose of BCG. As above, any disease-free interval of 2 years or more following adequate BCG course should be re-assessed and treated as a second primary urothelial carcinoma. Please contact the Sponsor if there are questions.
- Ineligible to receive radical cystectomy (medically unfit) or refusal of radical cystectomy based on investigator assessment.
- Demonstrate adequate organ function, defined as:
- Aspartate transaminase (AST), alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN);
- Total serum bilirubin ≤ 1.5 × ULN (OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN);
- Absolute neutrophil count (ANC) ≥ 1,000 cells/mm^3;
- Hemoglobin ≥ 8 g/dL or ≥ 4.96 mmol/L;
- Platelet count ≥ 100,000 platelets/mm^3;
- Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 30 mL/min for patient with creatinine levels > 1.5 institutional ULN according to Cockcroft-Gault formula:
- Serum chemistries: Sodium, potassium, and calcium within normal limits (WNL) or Grade 1;
- International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN unless receiving anticoagulation therapy and INR or PT is within the therapeutic range of intended use of anticoagulants.
- NOTE: patients must be able to suspend, based on local practice, anticoagulant and anti-platelet therapy for study specific biopsies and procedures.
- Willing to use barrier contraception during sexual activity, starting with Day 1 for up to 6 weeks after each dose of CG0070.
- Meet the following regarding criteria to prevent pregnancy:
- Male patients able to father children must agree to use highly effective contraception method during the treatment period and for at least 120 days after the last dose of CG0070 and pembrolizumab;
- Female patients are eligible to participate if not pregnant, not breast feeding, and at least one of the following condition applies:
- Not woman of childbearing potential; or
- A woman of childbearing potential who agrees to follow the contraception guidance during the treatment period and for at least 150 days after the last dose of CG0070 and pembrolizumab.
- Patients must be willing to comply with study mandated cystoscopies, urine cytology, urograms, biopsies, and other procedures (including transurethral resection of bladder tumor [TURBT] or other resection for all Ta/T1 disease). Patients who withdraw consent for these procedures will be withdrawn from the trial.
- Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
- Has current or past history of muscle invasive (T2 or higher stage) or locally advanced (T3/T4, any N) or metastatic bladder cancer.
- Has urothelial carcinoma in the upper genitourinary tract (kidneys, renal collecting systems, ureters) or prostatic urethra (including CIS of the urethra) within 24 months of enrollment.
- Has received systemic anti-cancer therapy, including investigational agents, within 4 weeks of Day 1.
- NOTE: For participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- Has received prior systemic treatment, radiation therapy, or surgery for bladder cancer other than TURBT or bladder biopsies.
- Has any of the following within the 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, pulmonary embolus, uncontrolled hypertension or uncontrolled congestive heart failure.
- Has used excluded anti-viral medication (e.g., interferon/peg-interferon, ribavirin, etc.) within 14 days of Day 1 and that cannot be suspended throughout for at least 14 days prior to and after the each treatment with CG0070.
- Has had prior treatment with any human adenovirus serotype 5 based therapy (e.g., Ad-interferon or Instiladrin).
- Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended for per protocol biopsies and other procedures as per standard of care.
- Has significant immunodeficiency due to underlying illness (e.g., known HIV/AIDS).
- Has received systemic immunosuppressive medication including high-dose corticosteroids (e.g., systemic corticosteroids > 10 mg prednisone or equivalent), within 28 days prior to Day 1.
- NOTE: Patients must not be receiving doses of > 10 mg/day of prednisone or equivalent at the time of study entry or during the study (unless used to treat pembrolizumab related toxicity) and corticosteroids may not be used for premedication.
- Has had an allogenic tissue/solid organ transplant.
- Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
- NOTE: No testing for Hepatitis B and Hepatitis C is required unless mandated by a local health authority.
- SOUTH KOREA ONLY: Is positive for Hepatitis B surface antigen (HbsAg reactive) or positive for Hepatitis C RNA by PCR (HCV RNA [qualitative] is detected). Testing is required within 8 weeks of Day 1.
- Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years except the following:
- Localized, low-risk, prostate cancer (e.g., stage < T2B, Gleason score < 7 treated with curative intent and without prostate-specific antigen (PSA) specific;
- Low risk prostate cancer (e.g., Stage T1/T2a, Gleason score < 7, and PSA ≤ 10 ng/mL) who are treatment naïve and undergoing active surveillance;
- Cancers with negligible risk of metastasis or death (e.g., risk of death or metastasis < 5% at 5 years) that have been treated with curative intent and no evidence of recurrence or metastasis (e.g., adequately treated CIS of the cervix, basal or squamous cell skin cancer, or ductal CIS of the breast).
- Has an active infection requiring systemic therapy (e.g., urinary tract infection or other active infection).
- Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- Has a history of interstitial lung disease.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
- NOTE: COVID-19 vaccination is allowed but please contact the Sponsor if the patient has received, or plans to receive, live COVID-19 vaccination and document the date and type of COVID-19 vaccine received.
- Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
- Has not recovered (i.e., to ≤ Grade 1 or to Baseline status) from AEs due to a previously administered agent.
- NOTE: Patients with ≤ Grade 2 neuropathy or having any alopecia are an exception to this criterion and may qualify for the study.
- NOTE: If patient received major surgery, they must be at least 4 weeks from surgery AND have recovered adequately from the toxicity and/or complications from the surgery prior to starting therapy.
- NOTE: Patients receiving prior radiation must have recovered (< Grade 1) from any acute toxicity.
- NOTE: Patients having irreversible but not clinically significant toxicity are eligible.
- Has an illness, metabolic dysfunction, physical examination finding, or clinical laboratory finding that gives reasonable suspicion of a disease or condition that would contraindicate study treatment or that would limit compliance with study requirements.
- Is pregnant, currently breastfeeding or intending to breastfeed, within the projected duration of the trial beginning at Screening through 150 days after the last study treatment.
- Cannot tolerate study-related biopsies, IVE administration, or 1-hour bladder hold of CG0070.
- IVE therapy within 8 weeks prior to beginning study treatment with the exception of cytotoxic agents (e.g., Mitomycin C, gemcitabine, doxorubicin, and epirubicin) when administered as a single instillation immediately following a TURBT procedure which is permitted up to 14 to 60 days prior to beginning study treatment.
Eligibility last updated 4/18/22. Questions regarding updates should be directed to the study team contact.
Publications are currently not available