Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03521830
Recruitment Status : Recruiting
First Posted : May 10, 2018
Last Update Posted : December 6, 2018
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Basal Cell Carcinoma Drug: Nivolumab Drug: Ipilimumab Phase 2

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Patients from Arm A can crossover to Arm B
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Nivolumab Alone or Plus Ipilimumab for Patients With Locally-Advanced Unresectable or Metastatic Basal Cell Carcinoma
Actual Study Start Date : November 27, 2018
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : November 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Previous Systemic Therapy Patients
Arm A: Nivolumab 480mg IV q4weeks for up to 48 weeks (six 8-week cycles)
Drug: Nivolumab
480mg IV every 4 weeks
Other Name: Opdivo

Experimental: Progression after anti-PD-1 therapy
Arm 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.
Drug: Nivolumab
480mg IV every 4 weeks
Other Name: Opdivo

Drug: Ipilimumab
1mg/kg IV every 4 weeks for 4 doses
Other Name: Yervoy




Primary Outcome Measures :
  1. Objective Response Rate [ Time Frame: 5 years ]
    Objective response rate per the revised Response Evaluation Criteria in Solid Tumors (RECIST 1.1)


Secondary Outcome Measures :
  1. progression-free survival [ Time Frame: 5 years ]
    duration of time from start of treatment to time of progression or Basal Cell Carcinoma specific death, whichever occurs first

  2. duration of response [ Time Frame: 5 years ]
    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

  3. overall survival [ Time Frame: 5 years ]
    measured from the time of enrollment until death



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03521830


Contacts
Layout table for location contacts
Contact: Trish Brothers, R.N., B.S.N. 410-955-6605 pbrothe1@jhmi.edu

Locations
Layout table for location information
United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21231
Contact: Evan Lipson, MD    410-502-5977    evanlipson@jhmi.edu   
Contact: Trish Brothers, RN, BSN    410-955-6605    pbrothe1@jhmi.edu   
Principal Investigator: Evan Lipson, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Investigators
Layout table for investigator information
Principal Investigator: Evan J Lipson, M.D. Johns Hopkins University

Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03521830     History of Changes
Other Study ID Numbers: J1866
IRB00166274 ( Other Identifier: JHM IRB )
First Posted: May 10, 2018    Key Record Dates
Last Update Posted: December 6, 2018
Last Verified: December 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Basal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Basal Cell
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents