Clinical Trials /

Nivolumab Alone or Plus Ipilimumab for Patients With Locally-Advanced Unresectable or Metastatic Basal Cell Carcinoma

NCT03521830

Description:

This is a phase 2 trial assessing the efficacy of nivolumab, alone or in combination with ipilimumab in treating patients with locally-advanced unresectable or metastatic basal cell carcinoma.

Related Conditions:
  • Basal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab Alone or Plus Ipilimumab for Patients With Locally-Advanced Unresectable or Metastatic Basal Cell Carcinoma
  • Official Title: Nivolumab Alone or Plus Ipilimumab for Patients With Locally-Advanced Unresectable or Metastatic Basal Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: J1866
  • SECONDARY ID: IRB00166274
  • SECONDARY ID: CA209-8DP
  • NCT ID: NCT03521830

Conditions

  • Basal Cell Carcinoma

Interventions

DrugSynonymsArms
NivolumabOpdivoPrevious Systemic Therapy Patients
IpilimumabYervoyProgression after anti-PD-1 therapy

Purpose

This is a phase 2 trial assessing the efficacy of nivolumab, alone or in combination with ipilimumab in treating patients with locally-advanced unresectable or metastatic basal cell carcinoma.

Detailed Description

      This is an open-label, phase 2 signal-seeking study.

      Screening will begin by establishing a participant's initial eligibility and signing of the
      informed consent document. Eligible, enrolled patients will be assigned to one of 2 cohorts
      in a non-randomized fashion according to prior treatment history.

      Cohort A: Patients who have not received prior anti-PD-1 therapy, but may have previously
      experienced progressive disease or intolerance after up to two other systemic therapies
      (e.g., one or more hedgehog signaling pathway inhibitors) will receive nivolumab 480 mg IV
      every 4 weeks for up to 48 weeks.

      Cohort B: Patients whose disease has progressed after anti-PD-1, either as a part of this
      trial or outside of this trial, may receive nivolumab 480mg IV q4weeks x 12 doses +
      ipilimumab 1mg/kg IV q4 weeks x 4 doses, then q12weeks x 2 doses.

      Patients enrolled on Cohort A who demonstrate PD after nivolumab monotherapy may, if
      appropriate in the opinion of the investigator, move to Cohort B.

      Discontinuation of nivolumab or ipi+nivo may be at the discretion of the investigator under
      circumstances including but not limited to the following:

        1. A complete response to therapy.

        2. A severe IMAR, defined as Grade 3 or greater.

        3. Documented disease progression warranting alternative systemic therapy

        4. Intercurrent illness that prevents further administration of study treatment

        5. Noncompliance with trial treatment or procedure requirements, or administrative reasons
    

Trial Arms

NameTypeDescriptionInterventions
Previous Systemic Therapy PatientsActive ComparatorArm A: Nivolumab 480mg IV q4weeks for up to 48 weeks (six 8-week cycles)
  • Nivolumab
Progression after anti-PD-1 therapyExperimentalArm B: ipilimumab 1mg/kg IV q4 weeks x 4 doses + nivolumab 480mg IV q4weeks followed by nivolumab 480mg IV q4weeks for up to 48 total weeks of therapy.
  • Nivolumab
  • Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          1. Signed Written Informed Consent

               1. Subjects must have signed and dated an Institutional Review Board (IRB)-approved
                  written informed consent form in accordance with regulatory and institutional
                  guidelines. This must be obtained before the performance of any protocol related
                  procedures that are not part of normal subject care.

               2. Subjects must be willing and able to comply with scheduled visits, treatment
                  schedule, laboratory tests, and other requirements of the study

          2. Type of Participant and Target Disease Characteristics

               1. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

               2. Participants with histologically confirmed Basal Cell Carcinoma with disease that
                  is considered by the investigator to be unresectable or metastatic.

             i. ARM A: patients may have received up to two prior systemic therapies including
             hedgehog pathway inhibitors ii. ARM B: patients may have received up to two prior
             systemic therapies including hedgehog pathway inhibitors. In addition, Basal Cell
             Carcinoma must have progressed after anti-PD-1 therapy, the most recent dose
             administered within 3 months of starting therapy on this trial. No other therapy may
             have been received between prior anti-PD-1 therapy and on-study ipi + nivo.

             c. Patients may not have received prior T cell modulating agents (e.g., anti-CTLA-4,
             anti-PD-L1, anti-LAG-3, anti-KIR, etc.), except anti-PD-1 per ARM B specifications,
             above.

             d. At least one measurable lesion by the revised Response Evaluation Criteria in Solid
             Tumors (RECIST 1.1) e. Participants with Gorlin syndrome will be permitted to enroll
             in the study. f. Male or female, aged 18 years or older

          3. Laboratory Testing Requirements

             Screening laboratory values obtained within -28 +/- 3 days of first dose must meet the
             following criteria:

               1. White Blood Cells greater than or equal to 2000/μL

               2. Neutrophils greater than or equal to 1500/μL

               3. Platelets greater than or equal to 100 x 10³/μL

               4. Hemoglobin greater than or equal to 9.0 g/dL

               5. Serum creatinine less than or equal to 1.5 x Upper Limit of Normal (ULN)or
                  creatinine clearance (CrCl) greater than or equal to 40 mL/minute (using
                  Cockcroft/Gault formula)

               6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or
                  equal to 3 x ULN, except in patients with liver metastases whose values may be
                  less than or equal to 5 x ULN

               7. Total Bilirubin less than or equal to 1.5 x ULN (except subjects with Gilbert
                  Syndrome who may have total bilirubin less than or equal to 3.0 mg/dL)

          4. Reproductive Status

               1. Women of childbearing potential (WOCBP) must have a negative serum or urine
                  pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24
                  hours prior to the initial administration of study drug, then every 4 weeks +/- 1
                  week thereafter for the duration of treatment with study drug(s).

               2. Women must not be breastfeeding.

               3. WOCBP must agree to follow instructions for method(s) of contraception from the
                  time of enrollment for the duration of treatment with study drug(s) plus
                  approximately 5 half-lives of study drug(s) plus 30 days (duration of ovulatory
                  cycle) for a total of 5 months post treatment completion.

               4. Males who are sexually active with WOCBP must agree to follow instructions for
                  method(s) of contraception for the duration of treatment with study drug(s) plus
                  approximately 5 half-lives of study drug(s) plus 90 days (duration of sperm
                  turnover) for a total of 7 months post-treatment completion.

               5. Azoospermic males and those who are continuously not heterosexually active are
                  exempt from contraceptive requirements.

               6. WOCBP who are continuously not heterosexually active are exempt from
                  contraceptive requirements, however they must still undergo pregnancy testing as
                  described in this section.

        Exclusion Criteria:

          1. Medical Conditions

               1. Pregnant or nursing women

               2. Central nervous system metastases, unless stable for at least 4 weeks and no
                  longer requiring steroid therapy.

               3. Patients with an autoimmune disease or with a condition requiring systemic
                  treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or
                  other immunosuppressive medications may be permitted to enroll only after
                  discussion with the study P.I.

               4. Participants with human immunodeficiency virus (HIV) or acquired immunodeficiency
                  syndrome (AIDS)

               5. Viral hepatitis

             i. Participants with active hepatitis B (positive hepatitis B surface antigen [HBsAg]
             or hepatitis C virus (HCV) (positive HCV RNA) are excluded ii. Patients with past
             Hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence
             of hepatitis B core antibody [HBcAb] and the absence of HBsAg) are not ineligible, but
             HBV DNA quantification must be performed and results discussed with the P.I.

             iii. HBV carriers or those participants requiring antiviral therapy are not eligible
             to participate.

             iv. Patients positive for HCV antibody are eligible only if polymerase chain reaction
             (PCR) is negative for HCV RNA after discussion with the study P.I.

             f. Participants with a prior malignancy active within the previous 2 years may be
             permitted to enroll only after discussion with the study P.I. Examples might include
             locally curable cancers that have been apparently cured, such as squamous cell skin
             cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or
             breast.

             g. Organ transplant recipients with a functioning allograft will be excluded from this
             study.

             h. For Cohort B, patients may be excluded from the study if they previously
             experienced a toxicity to immunotherapy that, in the opinion of the investigator,
             would make it unsafe to restart therapy. Examples may include a Grade 3 or greater
             immune mediated adverse event that was considered related to previous immunotherapy
             and required immunosuppressive therapy, or an immune mediated adverse event that was
             considered related to previous immunotherapy and is still > grade 1 despite
             administration of immunosuppressive therapy. Exceptions may include Grade 3
             ophthalmologic immune-mediated events that improved to Grade 1 within 2 weeks after
             topical therapy only, or Grade 3 endocrine immune-mediated events that did not result
             in symptoms lasting >6 weeks and are not requiring >7.5mg prednisone or equivalent per
             day.

          2. Allergies and Adverse Drug Reaction

               1. History of severe allergy or hypersensitivity to study drug components.

               2. Patients with a history of a severe toxicity to an immune checkpoint blocking
                  drug may be permitted to enroll only after discussion with the study P.I.

          3. Other Exclusion Criteria

               1. Prisoners or participants who are incarcerated may be permitted to enroll only
                  after discussion with the study P.I.

               2. Participants who are detained for treatment of either a psychiatric or physical
                  (e.g., infectious disease) illness.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate
Time Frame:5 years
Safety Issue:
Description:Objective response rate per the revised Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Secondary Outcome Measures

Measure:progression-free survival
Time Frame:5 years
Safety Issue:
Description:duration of time from start of treatment to time of progression or Basal Cell Carcinoma specific death, whichever occurs first
Measure:duration of response
Time Frame:5 years
Safety Issue:
Description:duration of time that measurement criteria are met for Complete Response or Partial Response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented
Measure:overall survival
Time Frame:5 years
Safety Issue:
Description:measured from the time of enrollment until death

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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