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 (ATLANTIS Trial)
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 to determine a difference in progression-free survival (PFS) by an Independent Review Committee (IRC) between lurbinectedin (PM01183)/doxorubicin (DOX) and the control arm (CAV) or topotecan and to analyze the median overall survival (OS) and mid- and long-term overall survival (OS at 12, 18 and 24 months).
Voluntary written informed consent
Adult patients ≥ 18 years
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.
Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2.
Adequate hematological, renal, metabolic and hepatic function within 7-10 days prior to randomization
At least three weeks since last prior anticancer treatment and adequate recovery from prior treatment toxicity
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.
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.
More than one prior chemotherapy-containing line(re-challenge with the same initial regimen is not allowed)
Patients who never received platinum-containing regimen for Small-cell Lung Cancer (SCLC)
Prior treatment with PM01183, topotecan or anthracyclines.
Limited-stage patients who are candidates for local or regional therapy
Impending need for palliative RT or surgery for pathological fractures and/or for medullary compression within four weeks prior to randomization.
Symptomatic or progressing or steroid requiring Central Nervous System (CNS) involvement disease at least four weeks prior to randomization
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.