Clinical Trials /

Cemiplimab in AlloSCT/SOT Recipients With CSCC

NCT04339062

Description:

In this research study, Cemiplimab is being evaluated as a treatment for advanced cutaneous squamous cell carcinoma in participants who have previously received an allogeneic hematopoietic stem cell transplant or kidney transplant. - This research study involves the following drug(s): - Cemiplimab - Everolimus or Sirolimus - Prednisone

Related Conditions:
  • Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Cemiplimab in AlloSCT/SOT Recipients With CSCC
  • Official Title: Safety and Efficacy of Cemiplimab (PD-1 Blockade) in Selected Organ Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma (CONTRAC)

Clinical Trial IDs

  • ORG STUDY ID: 19-817
  • NCT ID: NCT04339062

Conditions

  • Cutaneous Squamous Cell Carcinoma
  • Advanced Cancer

Interventions

DrugSynonymsArms
CemiplimabLibtayoCohort 1 Cemiplimab
EverolimusAfinitor, ZortressCohort 2 Cemiplimab + Everolimus/Sirolimus + Prednisone
SirolimusRapamuneCohort 2 Cemiplimab + Everolimus/Sirolimus + Prednisone
PrednisoneDeltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DSCohort 2 Cemiplimab + Everolimus/Sirolimus + Prednisone

Purpose

In this research study, Cemiplimab is being evaluated as a treatment for advanced cutaneous squamous cell carcinoma in participants who have previously received an allogeneic hematopoietic stem cell transplant or kidney transplant. - This research study involves the following drug(s): - Cemiplimab - Everolimus or Sirolimus - Prednisone

Detailed Description

      -  This an open-label, two cohort, phase I/II research study to evaluate the safety and
           effectiveness of Cemiplimab as a treatment for advanced cutaneous squamous cell
           carcinoma in participants who have received allogeneic hematopoietic stem cell or kidney
           transplants.

        -  The research study procedures include screening for eligibility, study treatment,
           participant evaluations and safety follow-up visits. It is expected that about 12 people
           will take part in this research study.

             -  Participants will be divided into two groups (cohorts) of allogeneic hematopoietic
                stem cell recipients or kidney transplants recipients.

             -  Allogeneic hematopoietic stem cell recipients will only receive the study treatment
                drug of Cemiplimab.

             -  Kidney transplant recipients will receive the study treatment drug of Cemiplimab
                along with the immunosuppressant drugs of Everolimus or Sirolimus and Prednisone to
                prevent kidney rejection.

      The U.S. Food and Drug Administration (FDA) has approved Cemiplimab as a treatment option for
      patients with advanced cutaneous squamous cell cancer, but the FDA has not approved the use
      of Cemiplimab in participants who have received allogeneic hematopoietic stem cell
      transplants or kidney transplants in the past.

      -- Cemiplimab is a type of drug called a monoclonal antibody. Antibodies are proteins
      naturally found in your blood that fight infections. A monoclonal antibody is a special kind
      of antibody that is manufactured as a medication to target specific proteins in the body that
      may be involved this type of cancer.

      Cemiplimab is a human monoclonal anti-PD-1 antibody that works by blocking the programmed
      death-1 (PD-1), a cell receptor on immune cells that is involved in preventing immune cells
      from destroying other cells. Blocking the receptor is expected to help immune cells attack
      cancer cells.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1 CemiplimabExperimentalParticipants who received allogeneic hematopoietic stem cell transplant -- Cemiplimab: via IV, flat predetermined dosage every 21 days
  • Cemiplimab
Cohort 2 Cemiplimab + Everolimus/Sirolimus + PrednisoneExperimentalParticipants who received a kidney transplant will receive Cemiplimab via IV, flat predetermined dosage every 21 days Everolimus or Sirolimus-least 7-10 days prior to receiving the first dose of cemiplimab (Cycle 1, Day 1) and then daily while receiving Cemiplimab Prednisone 40 mg orally the day prior to the start of cemiplimab dosing (Cycle 1, Day 1) and then daily at tapering doses while receiving Cemiplimab
  • Cemiplimab
  • Everolimus
  • Sirolimus
  • Prednisone

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically confirmed, advanced or metastatic cutaneous squamous
             cell carcinoma (cSCC) with 1 or more measurable lesions (greater than or equal to 1
             cm).

          -  A history of either (Cohort 1) allogeneic hematopoietic stem cell transplant
             (alloHSCT) and ≥ 2 years or 730 days from day 0 of their HSCT with adequate bone
             marrow function (see Section 3.1.6) and off of all systemic immunosuppression (topical
             agents permitted) for at least 3 months prior to enrollment; sequelae of chronic GVHD
             is permitted (i.e. chronic dry eyes, sclerodermatous skin changes, etc.) if the
             patient is not on systemic immunosuppression, or (Cohort 2) a renal transplant with a
             functioning allograft (at least 6 months from allograft transplant) as determined by
             estimated glomerular filtration (GFR) rate (CKD-EPI equation [40], Appendix A) ≥ 30
             mL/min, baseline proteinuria lower than 0.5 g/day (spot urine protein-creatinine
             ratio), and off antiproliferative immunosuppressive medications. Willing to provide
             blood and tissue from diagnostic biopsies.

          -  Age 18 years or older.

          -  ECOG performance status ≤ 2 (Karnofsky ≥ 60%, see Appendix B).

          -  Participants must have adequate organ and marrow function as defined below:

               -  leukocytes ≥ 2,200/mcL

               -  absolute neutrophil count ≥ 1,000/mcL

               -  platelets ≥ 90,000/mcL

               -  total bilirubin within normal institutional limits (except in cases where Gilbert
                  syndrome is known or suspected, where total bilirubin should be < 3 mg/dL)

               -  AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal

               -  creatinine ≤ 1.5 × institutional upper limit of normal OR

               -  estimated GFR ≥ 30 mL/min/1.73 m2 for participants with creatinine levels above
                  institutional normal (CKD-EPI equation).

               -  urine protein/creatinine ratio < 0.5 (equal to less than 500 mg of proteinuria
                  per day)

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  A prior history of acute GVHD that has resolved, or sequelae of chronic GVHD following
             allo-HSCT is permitted. Active acute GVHD patients are excluded.

          -  Women of childbearing potential (WOCBP) must agree to use at least 1 highly effective
             form of contraception (refer to Appendix C for examples). WOCBP should plan to use an
             adequate method to avoid pregnancy for up to 7 months (30 days plus the time required
             for cemiplimab to undergo five half-lives) after the last dose of investigational
             drug.

        "Women of childbearing potential (WOCBP)" is defined as any female who has experienced
        menarche, who has not undergone surgical sterilization (hysterectomy or bilateral
        oophorectomy), who is not postmenopausal, who is sexually active with a male partner.
        Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the
        absence of other biological or physiological causes. In addition, women under the age of 55
        must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.

          -  Women of childbearing potential, as defined above, 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 start of cemiplimab.

          -  Men who are sexually active with WOCBP must agree to use any contraceptive method with
             a failure rate of less than 1% per year. Men who are sexually active with WOCBP will
             be instructed to adhere to contraception for a period of 7 months after the last dose
             of investigational product. Women who are not of childbearing potential as defined
             above, and azoospermic men) do not require contraception. See Appendix C for further
             guidance on contraception

        Exclusion Criteria:

          -  Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have unresolved
             toxicities from prior anti-cancer therapy more than 4 weeks earlier, defined as not
             resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse
             Events (CTCAE, version 5.0), grade 0 or 1.

          -  Participants who are receiving any other investigational agents.

          -  For Cohort 1 allo-HSCT patients enrolling to the study, corticosteroid doses > 10 mg
             of prednisone daily or equivalent within 4 weeks of the first dose of PD-1 inhibitor
             are prohibited. For Cohort 2 renal transplant patients enrolling to the study,
             corticosteroid use is permitted if used as part of their immunosuppressive regimen for
             graft protection prior to enrollment.

          -  Existing significant autoimmune conditions. Patients with a history of Hashimoto
             thyroiditis who are stable on replacement hormone therapy are not excluded.

          -  Known human immunodeficiency virus carrier or a diagnosis of immunodeficiency. Any
             positive test result for hepatitis B virus or hepatitis C virus indicating presence of
             virus, e.g., Hepatitis B surface antigen (HBsAg, Australia antigen) positive, or
             Hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative).

          -  Kidney transplant recipients with active acute rejection.

          -  Allergy to cemiplimab or any of its components.

          -  Any prior exposure to the phosphoinositide 3-kinase inhibitor idelalisib.

          -  Subject who has been treated with immunotherapy. This includes prior treatment with
             anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug
             specifically targeting T-cell co-stimulation or checkpoint pathways (including
             chimeric antigen receptor [CAR] T cell therapies). Prior topical or intralesional
             immunotherapies (e.g. imiquimod, talimogene laherparepvec) are allowed.

          -  Subject with known and untreated brain metastases should be excluded from this
             clinical trial because of their poor prognosis and because they often develop
             progressive neurologic dysfunction that would confound the evaluation of neurologic
             and other adverse events. However, baseline brain imaging is not required prior to
             enrollment in the study if patients are asymptomatic. Patients at least 4 weeks out
             from metastatic central nervous system (CNS) treatment are permitted to enroll, if
             they are asymptomatic, radiographically stable per the investigator, and on stable
             doses of anti-epileptic drugs (AEDs) and oral corticosteroids (for Cohort 1 only, the
             patient must be on 10 mg of prednisone daily equivalent dosing or less, see 3.2.2) at
             the time of enrollment.

          -  Participants receiving any medications or substances that are strong inhibitors or
             inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly
             changing, it is important to regularly consult a frequently-updated list such as
             http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as
             the Physicians' Desk Reference may also provide this information. As part of the
             enrollment/informed consent procedures, the patient will be counseled on the risk of
             interactions with other agents, and what to do if new medications need to be
             prescribed or if the patient is considering a new over-the-counter medicine or herbal
             product.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
             arrhythmia.

          -  Known non-infectious pneumonitis or any history of interstitial lung disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of Dose Limiting Toxicity
Time Frame:first dose of study treatment up to 100 days
Safety Issue:
Description:Patient safety will be assured by monitoring the proportions of patients who have observed GVHD in Cohort 1 or renal transplant rejection in Cohort 2 when 3 or 6 patients have been enrolled into each cohort. Participants will be evaluable for toxicity from the time of their first treatment.

Secondary Outcome Measures

Measure:Progression Free Survival Rate
Time Frame:Time from registration to the earlier of progression or death due to any cause up to 1 year
Safety Issue:
Description:Per RECIST v1.1, at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Per WHO criteria, at least a 25% increase in the sum of the product of the two longest diameters among all lesions, or at least 25% increase in any 1 lesion.
Measure:Overall Survival Rate
Time Frame:Time from registration to death due to any cause, or censored at date last known alive up to 1 year
Safety Issue:
Description:Kaplan-Meier
Measure:Overall Response Rate
Time Frame:Up to 1 year
Safety Issue:
Description:Kaplan-Meier.
Measure:Therapeutic Response Rate
Time Frame:Up to 1 year
Safety Issue:
Description:Time-to-event endpoints will be summarized using the method of Kaplan-Meier. Point estimates for each endpoint will be presented with 90% confidence intervals derived using log(- log(survival)) methodology
Measure:Secondary Infection Rate
Time Frame:Up to 1 year
Safety Issue:
Description:Time-to-event endpoints will be summarized using the method of Kaplan-Meier. Point estimates for each endpoint will be presented with 90% confidence intervals derived using log(- log(survival)) methodology

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Cutaneous Squamous Cell Carcinoma
  • Advanced Cancer
  • Allogeneic hematopoietic stem cell transplant
  • Kidney transplant

Last Updated

April 8, 2020