Clinical Trials /

Study of CG0070 Combined With Nivolumab in Cisplatin Ineligible Patients With MIBC

NCT04610671

Description:

Investigators will evaluate the safety and efficacy of combination neoadjuvant therapy using intravesical CG0070 and IV Nivolumab in cisplatin ineligible patients with Muscle Invasive Bladder Cancer (MIBC).

Related Conditions:
  • Infiltrating Bladder Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1 Study of CG0070 Combined With Nivolumab in Cisplatin Ineligible Patients With MIBC
  • Official Title: A Phase 1 Study of CG0070 Combined With Nivolumab in Cisplatin Ineligible Patients With Muscle Invasive Bladder Cancer (MIBC)

Clinical Trial IDs

  • ORG STUDY ID: MCC-20575
  • NCT ID: NCT04610671

Conditions

  • Muscle-Invasive Bladder Carcinoma
  • Bladder Cancer

Interventions

DrugSynonymsArms
CG0070Participants Receiving CG0070 & Nivolumab
NivolumabParticipants Receiving CG0070 & Nivolumab

Purpose

Investigators will evaluate the safety and efficacy of combination neoadjuvant therapy using intravesical CG0070 and IV Nivolumab in cisplatin ineligible patients with Muscle Invasive Bladder Cancer (MIBC).

Trial Arms

NameTypeDescriptionInterventions
Participants Receiving CG0070 & NivolumabExperimentalBoth CG0070 (x 6 instillations) and nivolumab (x 2 doses) will be administered at their single-agent dose and schedule.
  • CG0070
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have histologically confirmed MIBC (T2-T4a, N0-N1, M0 per American
             Joint Commission on Cancer [AJCC]) pure or mixed histology urothelial carcinoma.
             Clinical node- positive (N1) patients are eligible provided the lymph nodes (LNs) are
             within the planned surgical LN dissection template.

          -  The initial TURBT that showed muscularis propria invasion should be within 90 days
             prior to beginning study therapy. Participants must have sufficient baseline tumor
             tissue from either initial or repeat TURBTs. The local site pathologist will be asked
             to estimate and record the rough approximate percentage of viable tumor in the TURBT
             sample (initial or repeat TURBT with highest tumor content) to document at least 20%
             viable tumor content prior to registration. This is to ensure adequate tissue is
             available to perform tumor infiltrating CD8+ T-cell assessment. (The actual CD8+ T
             cell analysis will be done by a Central Laboratory and will not be done prior to
             registration.)

          -  Participants must be ineligible for cisplatin-based chemotherapy due to any of the
             following:

               -  Creatinine clearance (CrCl) < 60 mL/min (with ECOG Performance Status (PS) 0-1)

               -  Hearing impaired ≥ Grade 2 by CTCAE criteria

               -  Neuropathy ≥ Grade 2 by CTCAE criteria

               -  Heart failure NYHA ≥ III

               -  ECOG ≥ 2

               -  Refusing to undergo cisplatin chemotherapy

          -  Participants must be medically fit for TURBT and radical cystectomy (RC)

          -  Age ≥ 18 years

          -  Ability to understand and willingness to sign IRB-approved informed consent

          -  Willing to provide tumor tissue, blood, and urine samples for research

          -  Adequate organ function as measured by the following criteria, obtained ≤ 4 weeks
             prior to registration:

               -  Absolute Neutrophil Count (ANC) ≥ 1000/mm3 (stable off growth factor within 4
                  weeks of first study drug administration)

               -  Platelets ≥ 100,000/mm3

               -  Hemoglobin ≥ 8 g/dL

               -  Serum Creatinine Clearance ≥ 20 mL/min using the Cockcroft-Gault formula

               -  ALT and AST ≤ 2.5x ULN

               -  Total Bilirubin ≤ 1.5x ULN (in the absence of previously diagnosed Gilbert's
                  disease)

        Exclusion Criteria:

          -  Women who are pregnant or breastfeeding, since the effects of nivolumab and CG0070 on
             the fetus or breastfeeding child are unknown. All sexually active females of
             childbearing potential (not surgically sterilized and between menarche and 1 year post
             menopause) must have a blood test to rule out pregnancy within 4 weeks prior to
             registration.

          -  Participant with local symptoms from bladder cancer, (e.g. gross hematuria, dysuria,
             etc.) who are deemed to be unable to complete the treatment protocol.

          -  Participant with active or prior documented autoimmune disease within the past 2 years
             prior to Screening or other immunosuppressive agent within 14 days of study treatment.
             NOTE: Participant with well controlled type 1 diabetes mellitus, vitiligo, Graves
             disease, Hashimoto's disease, eczema, lichen simplex chronicus, or psoriasis not
             requiring systemic treatment (within the past 2 years prior to Screening) are not
             excluded

          -  Participants who have concurrent upper urinary tract (i.e. ureter, renal pelvis)
             invasive urothelial carcinoma. Participants with history of non-invasive (Ta, T1, Tis)
             upper tract urothelial carcinoma that has been definitively treated with at least one
             post-treatment disease assessment (i.e. cytology, biopsy, imaging) that demonstrates
             no evidence of residual disease are eligible.

          -  Participants who have another malignancy that could interfere with the evaluation of
             safety or efficacy of the study drugs. Participants with a prior malignancy will be
             allowed without Principle Investigator approval in the following circumstances:

               -  Not currently active and diagnosed at least 3 years prior to the date of
                  registration.

               -  Non-invasive diseases such as low risk cervical cancer or any cancer in situ.

               -  Localized (early stage) cancer treated with curative intent (without evidence of
                  recurrence and intent for further therapy), and in which no chemotherapy was
                  indicated (e.g. low/intermediate risk prostate cancer, etc.). Participants with
                  other malignancies not meeting these criteria must be discussed prior to
                  registration.

          -  Participants who have received any prior immune checkpoint inhibitor (i.e. anti-KIR,
             anti-PD-1, anti- PD-L1, anti-CTLA4 or other).

          -  Participants who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or
             intra-pelvic), open biopsy or significant traumatic injury or specific anti-cancer
             treatment ≤ 4 weeks prior to starting study drug, or patients who have had placement
             of vascular access device ≤ 1 week prior to starting study drug, or who have not
             recovered from side effects of such procedure or injury.

          -  Participants who have clinically significant cardiac diseases deemed not fit for
             radical cystectomy, including any of the following:

               -  History or presence of serious uncontrolled ventricular arrhythmias.

               -  Clinically significant resting bradycardia.

               -  Any of the following within 3 months prior to starting study drug:
                  severe/unstable angina, Congestive Heart Failure (CHF), Cerebrovascular Accident
                  (CVA), Transient Ischemic Attack (TIA).

               -  Uncontrolled hypertension defined by a SBP ≥ 180 mm Hg and/or DBP ≥ 100 mm Hg,
                  with or without anti-hypertensive medication(s).

          -  Participants who have history of chronic active liver disease or evidence of acute or
             chronic Hepatitis B Virus (HBV) or Hepatitis C (HCV).

          -  Participants who have known diagnosis of human immunodeficiency virus (HIV) infection.
             Testing is not required in absence of clinical suspicion.

          -  Participants who have known diagnosis of any condition (e.g. post-hematopoietic or
             solid organ transplant, pneumonitis, inflammatory bowel disease, etc.) that requires
             chronic immunosuppressive therapy which cannot be stopped for the duration of the
             clinical trial. Usage of non-steroidal anti-inflammatory medications (NSAIDS) for the
             treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of
             gout are permitted.

          -  Participants with any serious and/or uncontrolled concurrent medical conditions (e.g.
             active or uncontrolled infection, uncontrolled diabetes) or psychiatric illness that
             could, in the investigator's opinion, cause unacceptable safety risks or potentially
             interfere with the completion of the treatment according to the protocol.

          -  Participants who have used any live viral vaccine for prevention of infectious
             diseases within 4 weeks prior to study drug(s). 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.

          -  Participants unwilling or unable to comply with the protocol.

          -  Participants with a known allergy to any of the study medications, their analogues, or
             excipients in the various formulations of any agent.

          -  Participants who participate in any other therapeutic clinical trials, including those
             with other investigational agents not included in this trial throughout the duration
             of this study.

          -  Use of excluded antiviral medication that cannot be suspended at least 14 days prior
             and for 14 days after the administration of any CG0070 treatment throughout the
             duration of the trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events
Time Frame:Up to 24 months after start of treatment
Safety Issue:
Description:Adverse events Grade 3 or higher will be graded according to the NC Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

Secondary Outcome Measures

Measure:Changes in intraepithelial CD8+ T cell density
Time Frame:Up to 24 months after start of treatment
Safety Issue:
Description:The changes in intraepithelial CD8+ T cell density from pre-treatment TURBT to post-treatment cystectomy samples will be assessed using a paired t-test or Wilcoxon signed rank test according to the distribution of changes in the CD8+T cell density. The distribution of changes will be investigated using the Anderson-Darling test.
Measure:Change in PD-L1 expression on tumor and immune cells
Time Frame:Up to 24 months after start of treatment
Safety Issue:
Description:The change in PD-L1 expression on tumor and immune cells from pre-treatment TURBT to post- treatment cystectomy samples will be assessed and analyzed using McNemar test for the change in the percentage of PD-L1 positivity before and after the study treatment, using the Stuart-Maxwell test with 4 ordered categories.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • Bladder

Last Updated

October 26, 2020