Clinical Trials /

Targeted Therapy With CDK4/6 Inhibitors in Chemo-Refractory, Rb Wild-Type Extensive SCLC

NCT04010357

Description:

The purpose of this study is to: - Test how well the study medicine Abemaciclib, a CDK4/6 inhibitor, works to shrink lung cancer tumors in the body. - Test the safety of Abemaciclib when given to participants with small cell lung cancer (SCLC).

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Targeted Therapy With CDK4/6 Inhibitors in Chemo-Refractory, Rb Wild-Type Extensive SCLC
  • Official Title: Targeted Therapy With CDK4/6 Inhibitors in Chemo-Refractory, Rb Wild-Type Extensive Small Cell Lung Cancer (SCLC), An Open Label Phase 2 Trial

Clinical Trial IDs

  • ORG STUDY ID: CASE1519
  • NCT ID: NCT04010357

Conditions

  • Small-cell Lung Cancer

Interventions

DrugSynonymsArms
Abemaciclib,LY2835219Abemaciclib

Purpose

The purpose of this study is to: - Test how well the study medicine Abemaciclib, a CDK4/6 inhibitor, works to shrink lung cancer tumors in the body. - Test the safety of Abemaciclib when given to participants with small cell lung cancer (SCLC).

Detailed Description

      This is a multicenter, non-randomized, phase 2, single arm study to determine the efficacy
      and safety of Abemaciclib as a single agent in patients with biopsy-proven wild type Rb
      extensive stage of SCLC,with platinum refractory disease (defined as no response after 1-2
      cycles of chemotherapy or relapse defined as initial response but relapse after completing
      platinum-based chemotherapy).

      Abemaciclib (CDK4/6 inhibitors) is an investigational drug that works by interrupting the
      rapid and uncontrolled growth of cancer cells. Some cancer cells develop because their cells
      overrun the molecular brakes that normally permit cell to divide only when they are needed to
      replace old ones. These brakes are regulated by a group of enzymes known as cyclin-dependent
      kinases (CDKs). Alterations causing over-activity of two of these enzymes, CDK4 andCDK6, are
      found in a variety of cancers, including small cell lung cancer with retinoblastoma (Rb)
      protein.The drugs work by selectively turning off the overactive CDK4 and CDK6. As a result,
      the cancer cells' division cycle is halted, preventing them from proliferating.

      The objectives of this study include determining:

        -  Overall Response Rate (ORR) after the first cycle (4 weeks) and then every 8 weeks.

        -  Progression Free Survival (PFS)assessed at 6 months and Overall Survival (OS).

        -  Safety and adverse events

        -  Duration of response in all responders
    

Trial Arms

NameTypeDescriptionInterventions
AbemaciclibExperimentalSubjects will receive Abemaciclib (200 mg), orally every 12 hours on days 1 to 28 of a 28-day cycle for a total of 56 doses per cycle. Subjects will be evaluated after 4 weeks (1st cycle) and then every 8 weeks (2 cycles) with radiographic imaging to assess response to treatment.
  • Abemaciclib,

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects must have histologically confirmed extensive stage small cell lung cancer.

          -  Pathology confirmed Retinoblastoma wild type tested by NGS.

          -  Subjects must have:

          -  Platinum refractory disease:defined as no response after 1-2 cycles of chemotherapy,
             or

          -  Relapse:defined as initial response but relapse after completing platinum-based
             chemotherapy.

          -  Subjects must have measurable disease per the Response Evaluation Criteria in Solid
             Tumors (RECIST), version 1.1.

          -  Subjects must have biopsy or archival tumor material available for biomarker analyses
             with confirmed availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue.

          -  Performance status: ECOG Performance status ≤ 2

          -  Patients who received chemotherapy must have recovered CTCAE Grade ≤1) from the acute
             effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy
             prior to enrollment. A washout period of at least 21 days is required between last
             chemotherapy dose and enrollment (provided the patient did not receive radiotherapy).
             Please refer to eligibility criteria for specific laboratory requirements.

          -  Patients who received radiotherapy must have completed and fully recovered from the
             acute effects of radiotherapy. A washout period of at least 14 days is required
             between end of radiotherapy and enrollment.

          -  Patients with treated brain metastases are eligible if follow-up brain imaging after
             CNS-directed therapy shows no evidence of progression.

          -  The patient is able to swallow oral medications.

          -  The patient has adequate organ function for all of the following criteria, as defined
             below:

               -  Hematologic system:

                    -  absolute neutrophil count (ANC) ≥1.5 × 10^9/L

                    -  Platelets ≥100 × 10^9/L

                    -  Hemoglobin ≥8g/dL (Patients may receive erythrocyte transfusions to achieve
                       this hemoglobin level at the discretion of the investigator. Initial
                       treatment must not begin earlier than the day after the erythrocyte
                       transfusion).

               -  Hepatic system:

                    -  Total bilirubin ≤1.5 × ULN Patients with Gilbert's syndrome with a total
                       bilirubin ≤2.0 times upper limit of normal (ULN) and direct bilirubin within
                       normal limits are permitted.

                    -  Alanine aminotransferase (ALT) and aspartate aminotransferas (AST) ≤3 × ULN.

          -  The effects of the study medication on the developing human fetus are unknown. For
             this reason, women of child-bearing potential and men must agree to use adequate
             contraception (double barrier method of birth control or abstinence) throughout study
             participation and for 6 months after completing treatment.

          -  Subjects must have the ability to understand and the willingness to sign a written
             informed consent document.

        Exclusion Criteria:

          -  Prior treatment toxicities not resolved to ≤ Grade 1 according to NCI CTCAE Version
             5.0 (except alopecia,and neuropathy).

          -  Subjects receiving any other investigational agents.

          -  The patient has serious preexisting medical condition(s) that would preclude
             participation in this study (for example, interstitial lung disease, severe dyspnea at
             rest or requiring oxygen therapy, history of major surgical resection involving the
             stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a
             preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).

          -  Females who are pregnant or lactating.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to Abemaciclib.

          -  Subjects with uncontrolled intercurrent illness including, syncope of cardiac
             etiology, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, sudden cardiac arrest, or psychiatric illness/social situations that would
             limit compliance with study requirements.

          -  The patient has active bacterial infection (requiring intravenous [IV] antibiotics at
             time of initiating study treatment), fungal infection, or detectable viral infection
             (such as known human immunodeficiency virus positivity or with known active hepatitis
             B or C [for example, hepatitis B surface antigen positive]. Screening is not required
             for enrollment.

          -  HIV-positive subjects on combination antiretroviral therapy are ineligible because of
             the potential for pharmacokinetic interactions with Abemaciclib. In addition, these
             subjects are at increased risk of lethal infections when treated with marrow
             suppressive therapy. Appropriate studies will be undertaken in subjects receiving
             combination antiretroviral therapy when indicated.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:Up to 2 years from start of study
Safety Issue:
Description:Overall Response Rate (ORR) defined as the proportion of subjects in the analysis population who have complete response (CR) or partial response (PR) using RECIST 1.1 criteria at any time during the study. Response for the primary analyses will be determined by independent radiology review. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Secondary Outcome Measures

Measure:Progression Free Survival (PFS) according to RECIST 1.1
Time Frame:At 6 months from start of study
Safety Issue:
Description:Defined as the time from allocation to the first documented disease progression according to RECIST 1.1 or death due to any cause, whichever occurs first.
Measure:Overall Survival (OS)
Time Frame:Up to 10 years from start of study.
Safety Issue:
Description:Overall Survival (OS) defined as the time from start of study to death due to any cause.
Measure:Safety and adverse events (AE's) and serious adverse events (SAE's) (CTCAE grade version 5.0).
Time Frame:Up to 90 days from end of treatment
Safety Issue:
Description:Safety and adverse events (AE's) (CTCAE grade version 5.0) will be assessed by quantifying the toxicities and grades experienced by subjects who have received Abemaciclib (Verzenio®[LY2835219]) including serious adverse events (SAEs). All SE's and grade 3 and 4 AE's will be tabulated.
Measure:Duration of response in all responders (DoR using RECIST 1.1)
Time Frame:Up to 2 years from start of study
Safety Issue:
Description:Duration of response in all responders (DoR using RECIST 1.1) assessed from the time that measurement criteria met until progressive disease is objectively documented. Progressive disease defined as at least a 20% increase in the sum of 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. The appearance of one or more new lesions is also considered progression.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Case Comprehensive Cancer Center

Trial Keywords

  • platinum refractory disease
  • Wild Type Rb Extensive Stage SCLC

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