Clinical Trial of Lurbinectedin (PM01183)/Doxorubicin Versus CAV or Topotecan as Treatment in Patients With Small-Cell Lung Cancer
Condition: Small-cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: Lurbinectedin (PM01183); Doxorubicin (DOX); Cyclophosphamide (CTX); Vincristine (VCR); Topotecan
Intervention MeSH terms: Cyclophosphamide; Doxorubicin; Vincristine; Topotecan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 613.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Phase III randomized clinical trial of lurbinectedin (PM01183)/doxorubicin (DOX) versus
      cyclophosphamide (CTX), doxorubicin (DOX) and vincristine (VCR) (CAV) or topotecan as
      treatment in patients with small-cell lung cancer (SCLC) who failed one prior
      platinum-containing line.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Voluntary written informed consent

          2. Adult patients ≥ 18 years

          3. Histologically or cytologically confirmed diagnosis of limited or extensive stage SCLC
             which failed one prior platinum-containing regimen and with a chemotherapy-free
             interval (CTFI, time from the last dose of first-line chemotherapy to the occurrence
             of progressive disease) ≥ 30 days. Small-cell carcinoma of unknown primary site with
             or without neuroendocrine features confirmed in histology test(s) performed on
             metastatic lesion(s) are eligible, if Ki-67/MIB-1 is expressed in >50% of tumor cells.

          4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2.

          5. Adequate hematological, renal, metabolic and hepatic function within 7-10 days prior
             to randomization

          6. At least three weeks since last prior anticancer treatment and adequate recovery from
             prior treatment toxicity

          7. Prior radiotherapy (RT): At least four weeks since completion of whole-brain
             irradiation, at least two weeks since completion of prophylactic cranial irradiation,
             and to any other site.

          8. Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP
             must agree to use a highly effective contraceptive measure up to six weeks after
             treatment discontinuation. Fertile male patients with WOCBP partners should use
             condoms during treatment and for four months following the last investigational
             medicinal product dose.

        Exclusion Criteria:

          1. More than one prior chemotherapy-containing line(re-challenge with the same initial
             regimen is not allowed)

          2. Patients who never received platinum-containing regimen for Small-cell Lung Cancer
             (SCLC)

          3. Prior treatment with PM01183, topotecan or anthracyclines.

          4. Limited-stage patients who are candidates for local or regional therapy

          5. Impending need for palliative RT or surgery for pathological fractures and/or for
             medullary compression within four weeks prior to randomization.

          6. Symptomatic or progressing or steroid requiring Central Nervous System (CNS)
             involvement disease at least four weeks prior to randomization

          7. Concomitant diseases/conditions:

             Angina, myocardial infarction, congestive heart failure or clinically significant
             valvular heart disease, arrhythmia, immunodeficiency (including known HIV
             seropositive), ongoing or treatment-requiring chronic liver disease, active infection,
             oxygen requirement within two weeks prior to randomization, diffuse interstitial lung
             disease (ILD) or pulmonary fibrosis, second invasive malignancy treated with
             chemotherapy and/or radiotherapy, invasive fungal infections requiring systemic
             treatment within 12 weeks of randomization.

          8. Pregnant or breast feeding women