Clinical Trial 18835

Cancer Type: Thoracic
Interventions:Adriamycin (doxorubicin); PM01183 (lurbinectedin); Topotecan; Vincristine; cyclophosphamide; cytoxan (cyclophosphamide); doxorubicin

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Alberto Chiappori

Overview

Study Title

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)

Summary

The main purpose of this clinical trial is to know if lurbinectedin (PM01183) when administered in combination with doxorubicin (DOX) is superior to the currently available standard treatment [topotecan, or a combination of cyclophosphamide (CTX), DOX and vincristine (VCR) known as CAV] in controlling small cell lung cancer (SCLC) evolution in patients who had progressed after receiving a platinum-containing line of treatment. Also the global effects (good or bad) of this combination will be compared to those of topotecan, a drug used and approved to treat this condition in the United States, the European Union and most Western countries. The knowledge obtained from this treatment combination may provide a way to fight against this type of cancer in a more specific way.

Objective

Primary: To determine a difference in progression-free survival PFS) by an Independent Review Committee IRC)between lurbinectedin (PM01183)/doxorubicin (DOX)and a control arm consisting of best Investigator's choice between cyclophosphamide (CTX), doxorubicin (DOX)and vincristine (VCR) CAV) or topotecan, as treatment in SCLC patients after failure of one prior platinumcontaining line. Secondary: To analyze: Overall survival (OS). Mid- and long-term survival (OS at 12, 18 and 24 months, respectively). Efficacy and safety profiles in the subgroups of thePM01183/DOX arm vs. CAV or topotecan. PFS by Investigators Assessment (IA). Antitumor activity according to the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. Safety profile. Patient-reported outcomes (PRO). Pharmacokinetics (PK) of the combination in patients treated in the experimental arm (PM01183/DOX). PK/pharmacodynamic (PDy) correlations in theexperimental arm, if any. Pharmacogenetics of known polymorphisms in patients treated in the experimental arm.

Inclusion Criteria

  • 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) less than or equal to 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.

  • Exclusion Criteria

  • 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
  • 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.
  • Pregnant or breast feeding women