Clinical Trials /

Durvalumab and Topotecan for the Treatment of Relapsed or Refractory Small Cell Lung Cancer

NCT04607954

Description:

This phase II trial studies the effects of durvalumab and topotecan in treating patients with extensive stage small cell lung cancer that has come back (relapsed) or has not responded to previous treatment with chemotherapy and immunotherapy (refractory). Monoclonal antibodies, such as durvalumab, may interfere with the ability of tumor cells to grow and spread. Topotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Giving durvalumab and topotecan may help kill more tumor cells and help patients live longer.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Durvalumab and Topotecan for the Treatment of Relapsed or Refractory Small Cell Lung Cancer
  • Official Title: Phase II Clinical Trial of Durvalumab (MEDI4736) and Topotecan in Patients With Relapsed Extensive Stage Small Cell Lung Cancer Previously Treated With Chemotherapy and Immunotherapy

Clinical Trial IDs

  • ORG STUDY ID: MC1923
  • SECONDARY ID: NCI-2020-08088
  • SECONDARY ID: MC1923
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT04607954

Conditions

  • Platinum-Sensitive Lung Small Cell Carcinoma
  • Recurrent Extensive Stage Lung Small Cell Carcinoma
  • Refractory Extensive Stage Lung Small Cell Carcinoma

Interventions

DrugSynonymsArms
DurvalumabImfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736Treatment (durvalumab, topotecan hydrochloride)
Topotecan HydrochlorideHycamptamine, Hycamtin, SKF S-104864-A, Topotecan HCl, topotecan hydrochloride (oral)Treatment (durvalumab, topotecan hydrochloride)

Purpose

This phase II trial studies the effects of durvalumab and topotecan in treating patients with extensive stage small cell lung cancer that has come back (relapsed) or has not responded to previous treatment with chemotherapy and immunotherapy (refractory). Monoclonal antibodies, such as durvalumab, may interfere with the ability of tumor cells to grow and spread. Topotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Giving durvalumab and topotecan may help kill more tumor cells and help patients live longer.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To evaluate whether combination of durvalumab with topotecan can increase the 6-month
      survival in patients with extensive stage small cell lung cancer who have progressed after
      initial combination of chemotherapy and immunotherapy.

      SECONDARY OBJECTIVES:

      I. To describe the safety and toxicity of durvalumab and topotecan in patients with extensive
      stage small cell lung cancer who have progressed after initial combination of chemotherapy
      and immunotherapy.

      II. To assess in a preliminary fashion antitumor efficacy of this approach by assessing
      overall survival, progression-free survival, and response rate.

      CORRELATIVE RESEARCH OBJECTIVE:

      I. Blood and tissue will be banked for future studies.

      OUTLINE:

      Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 and topotecan
      hydrochloride IV over 30 minutes on days 1-5. Cycles repeat every 21 days in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients without disease progression are followed up at
      30 days, every 6 weeks until disease progression, and then every 3 months thereafter for up
      to 5 years from enrollment. After completion of study treatment, patients with disease
      progression are followed every 3 months for up to 5 years from enrollment.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (durvalumab, topotecan hydrochloride)ExperimentalPatients receive durvalumab IV over 60 minutes on day 1 and topotecan hydrochloride IV over 30 minutes on days 1-5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Durvalumab
  • Topotecan Hydrochloride

Eligibility Criteria

        Inclusion Criteria:

          -  Histological or cytological confirmation of small cell lung cancer

          -  Prior treatment requirements:

               -  Relapsed or progressed after only one prior chemotherapy and PD-1 or PD-L1
                  inhibitor regimen

               -  Prior therapy must have been an etoposide platinum doublet combined with PD-1 or
                  PD-L1 inhibitor

               -  Must have "platinum-sensitive" disease according to the following definitions:

                    -  "Sensitive" disease: Relapse occurred > 90 days after completion of prior
                       therapy

                    -  "Refractory" disease: No response to therapy or relapse occurred =< 90 days
                       after completion of prior therapy

          -  Measurable disease

          -  Body weight > 30 kg

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

          -  Hemoglobin >= 9.0 g/dL (obtained =< 15 days prior to registration)

          -  Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 15 days prior to
             registration)

          -  Platelet count >= 100,000/mm^3 (obtained =< 15 days prior to registration)

          -  Albumin >= 2.5 mg/dL (obtained =< 15 days prior to registration)

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) or direct bilirubin =< ULN if
             total bilirubin is > 1.5 x ULN (obtained =< 15 days prior to registration)

          -  Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 2.5 x ULN (=< 5 x
             ULN for patients with liver involvement) (obtained =< 15 days prior to registration)

          -  Creatinine OR glomerular filtration rate (GFR) =< 1.5 x ULN OR GFR > 60 mL/min for
             patients with creatinine > 1.5 x ULN (obtained =< 15 days prior to registration)

          -  Negative pregnancy test done =< 7 days prior to registration, for persons of
             childbearing potential only

          -  Persons able to become pregnant OR able to father a child must be willing to use an
             adequate method of contraception while on treatment and for 120 days after last
             treatment

          -  Life expectancy >= 12 weeks

          -  Provide written informed consent

          -  Willingness to provide mandatory blood specimens for correlative research

          -  Willingness to provide mandatory tissue specimens for correlative research

          -  Willing to return to Mayo Clinic for follow-up (during the active monitoring phase of
             the study)

        Exclusion Criteria:

          -  Any of the following because this study involves an investigational agent whose
             genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
             unknown:

               -  Pregnant persons

               -  Nursing persons

               -  Persons of childbearing potential OR able to father a child who are unwilling to
                  employ adequate contraception

          -  Any of the following prior therapies:

               -  Live vaccine < 30 days prior to registration, including intranasal flu vaccine
                  (e.g. Flu-Mist[R]) (Note: Injected seasonal influenza vaccine is not "live")

               -  Surgery < 28 days prior to registration

               -  Chemotherapy or targeted small molecule therapy < 21 days prior to registration

               -  Radiation therapy < 21 days prior to registration

               -  Investigational therapy or investigational device < 14 days prior to registration

          -  Failure to recover to =< grade 1 (or baseline) from adverse events due to previously
             administered therapies or prior surgery. Exceptions: Neuropathy, fatigue, and/or
             alopecia may be grade 1

          -  Known active central nervous system (CNS) metastases. NOTE: Patients with previously
             treated brain metastases may participate provided all of the following are true:

               -  They are stable (without evidence of progression by imaging =< 4 weeks prior to
                  registration and any neurologic symptoms have returned to baseline)

               -  Have no evidence of new or enlarging brain metastases, and

               -  Are not using steroids =< 14 days prior to registration

          -  Known leptomeningeal disease

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Known active human immunodeficiency virus (HIV) infection (defined as patients who are
             not on anti-retroviral treatment and have detectable viral load and CD4+ < 500/ml).
             NOTE: HIV-positive patients who are well controlled on anti-retroviral therapy are
             allowed to enroll

          -  Active autoimmune disease requiring systemic treatment, documented history of severe
             autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive
             agents. NOTE: Exceptions are allowed for:

               -  Vitiligo

               -  Resolved childhood asthma/atopy

               -  Intermittent use of bronchodilators or inhaled steroids

               -  Daily steroids at dose of =< 10mg of prednisone (or equivalent)

               -  Local steroid injections

               -  Stable hypothyroidism on replacement therapy

               -  Stable diabetes mellitus on non-insulin therapy

               -  Sjogren's syndrome

          -  Current or prior use of immunosuppressive medication < 14 days prior to registration.
             The following are exceptions to this criterion:

               -  Intranasal, inhaled, topical steroids, or local steroid injections (e.g.,
                  intraarticular injection)

               -  Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
                  prednisone or its equivalent

               -  Steroids as premedication for hypersensitivity reactions (e.g., premedication for
                  computed tomography [CT] scans)

          -  Uncontrolled intercurrent illness including, but not limited to:

               -  Ongoing or active infection requiring systemic therapy

               -  Interstitial lung disease

               -  Serious, chronic gastrointestinal conditions associated with diarrhea (e.g.,
                  Crohn's disease or others)

               -  Known active hepatitis B (i.e., known positive hepatitis B virus [HBV] surface
                  antigen [HBsAg] reactive)

               -  Known active hepatitis C (i.e., positive for hepatitis C virus ribonucleic acid
                  [HCV RNA] detected by polymerase chain reaction [PCR])

               -  Known active tuberculosis (TB)

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Unstable cardiac arrhythmia or

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements (e.g., substance abuse)

          -  History of myocardial infarction =< 6 months, or congestive heart failure requiring
             use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm

          -  Hypersensitivity to durvalumab or any of its excipients

          -  Previous adverse event attributed to durvalumab or other PD-1 or PD-L1 directed
             therapy that led to drug discontinuation

          -  History of grade >= 3 immune-related adverse event or any grade of immune-related
             neurologic or ocular adverse event while receiving immunotherapy. Note: Patients who
             had endocrine adverse events =< grade 2 are allowed to enroll if they are stable on
             appropriate replacement therapy and asymptomatic

          -  Other active malignancy < 6 months prior to registration. EXCEPTIONS: Non-melanotic
             skin cancer, papillary thyroid cancer, or carcinoma-in-situ of the cervix, or others
             curatively treated and now considered to be at less than 30% risk of relapse
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:6-month survival rate
Time Frame:At 6 months
Safety Issue:
Description:The proportion of successes for 6-month overall survival (OS) rate will be estimated by the number of successes divided by the total number of evaluable patients. Ninety percent confidence intervals for the true success proportion will be calculated according to the exact binomial method.

Secondary Outcome Measures

Measure:Incidence of adverse events (AEs)
Time Frame:Up to 30 days post treatment
Safety Issue:
Description:AEs will be monitored using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine AE patterns.
Measure:Response rate
Time Frame:Up to 5 years
Safety Issue:
Description:Proportion of patients with a confirmed tumor response per Immune Response Evaluation Criteria in Solid Tumors (iRECIST) criteria. Response rate and 90% confidence intervals will be reported.
Measure:Progression-free survival (PFS)
Time Frame:From registration to the first of either disease progression or death from any cause, assessed up to 5 years
Safety Issue:
Description:PFS will be estimated using the method of Kaplan-Meier. Medians and 90% confidence intervals will be reported.
Measure:Overall survival (OS)
Time Frame:From registration to death from any cause, assessed to 5 years
Safety Issue:
Description:OS will be estimated using the method of Kaplan Meier. Medians and 90% confidence intervals will be reported.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Mayo Clinic

Last Updated

October 27, 2020