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)

Phase 1

• Conditions: Small-Cell Lung Cancer (SCLC); MedDRA version: 21.1Level: PTClassification code 10041067Term: Small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-001641-89-NL
• Lead Sponsor: Pharma Mar S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-07-20
• Last Update Posted: 4 May 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

1) Voluntary written informed consent of the patient obtained before any study-specific procedure.
2) Adult patients aged = 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) ECOG PS = 2.
5) Adequate hematological, renal, metabolic and hepatic function in an assessment performed within 7 days (+ 3 day window) of randomization:
a) Hemoglobin = 9.0 g/dl [patients may have received priorred blood cell (RBC) transfusion, if clinically indicated]; absolute neutrophil count (ANC) = 2.0 x 10^9/l and platelet count = 100 x 10^9/l.
b) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3.0 x upper limit of normal (ULN).
c) Total bilirubin = 1.5 x ULN or direct bilirubin = ULN.
d) Albumin = 3.0 g/dl.
e) Calculated creatinine clearance (CrCL) = 30 ml/minute (using Cockcroft and Gault’s formula).
f) Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan within normal range (according to institutional standards).
g) Creatine phosphokinase (CPK) = 2.5 x ULN (= 5.0 x ULN is acceptable if elevation is disease-related).
6) At least three weeks since last prior anticancer treatment and recovery to grade = 1 from any adverse event (AE) related to previous anticancer treatment (excluding sensory neuropathy, anemia, asthenia and alopecia, all grade = 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE,
v.4).
7) Prior radiotherapy (RT): At least four weeks since completion of whole-brain RT (WBRT), at least two weeks since completion of prophylactic cranial irradiation (PCI), and to any other site not previously specified.
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. Valid methods to determine the childbearing potential, adequate contraception and requirements for WOCBP partners are described in the Appendix 2 of the protocol. Fertile male patients with WOCBP partners should use condoms during treatment and for four months following the last investigational medicinal product (IMP) dose.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 400

Exclusion Criteria

1) More than one prior CHT-containing regimen (including patients re-challenged with same initial regimen).
2) Patients who never received any platinum-containing regimen for SCLC treatment.
3) Prior treatment with PM01183, topotecan or anthracyclines.
4) Limited-stage patients who are candidates for local or regional therapy, including PCI, thoracic RT or both, must have been offered that option and completed treatment or refused it prior to randomization.
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 steroid-requiring, or progressing CNSdisease involvement during at least four weeks prior to randomization (asymptomatic, non-progressing patients taking steroids in the process of already being tapered within two weeks prior to randomization are allowed).
7) Concomitant diseases/conditions:
a) History (within one year prior to randomization) or presence of unstable angina, myocardial infarction, congestive heart failure or clinically significant valvular heart disease.
b) Symptomatic or uncontrolled arrhythmia despite ongoing treatment.
c) Patients with any immunodeficiency, including those known to be or have been infected by human immunodeficiency virus (HIV).
d) Ongoing, treatment-requiring, non-neoplastic chronic liver disease of any origin. For hepatitis B, this includes positive tests for both Hepatitis B surface antigen (HBsAg) and quantitative Hepatitis B polymerase chain reaction (PCR). For hepatitis C, this includes positive tests for both Hepatitis C antibody and quantitative Hepatitis C PCR.
e) Active infection or increased risk due to external drainages.
f) Intermittent or continuous oxygen requirement within two weeks prior to randomization. Patients with confirmed or suspected diagnosis of diffuse interstitial lung disease (ILD) or pulmonary fibrosis.
g) Patients with a second invasive malignancy treated with CHT and/or RT. Patients with a previous malignancy that was completely resected with curative intention three or more years prior to randomization, and who has been continuously in remission since then will be permitted.
h) Limitation of the patient’s ability to comply with the treatment or to follow the protocol.
i) Documented or suspected invasive fungal infections requiring systemic treatment within 12 weeks of randomization.
8) Pregnant or breast feeding women.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified