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NCT Number: NCT02566993

Clinical Trial of Lurbinectedin (PM01183)/Doxorubicin Versus CAV or Topotecan as Treatment in Patients With Small-Cell Lung Cancer

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.

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Key information

Conditions

Small-cell Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Small Cell Lung Carcinoma Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Instituto Médico Especializado Alexander Fleming, C.a.b.a., Buenos Aires, Argentina

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About this study

Multicenter, open-label, randomized, controlled phase III clinical trial to evaluate and compare the activity and safety of an experimental arm consisting of PM01183/DOX combination followed by PM01183 alone, if applicable vs. best Investigator's choice between CAV or topotecan as a control arm, in SCLC patients who failed one prior platinum-containing line but no more than one prior chemotherapy-containing line.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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) ≤ 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

Treatment and study plan

lurbinectedin (PM01183)

Drug

Doxorubicin (DOX)

Drug

Cyclophosphamide (CTX)

Drug

Vincristine (VCR)

Drug

Topotecan

Drug

Primary outcomes

  1. Overall Survival (OS)

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).

Secondary outcomes

  1. Difference in Overall Survival Between Lurbinectedin/Doxorubicin (DOX) and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 12 Months

    Time frame: At 12 months

    Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).

  2. Difference in Overall Survival Between Lurbinectedin/DOX and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 18 Months

    Time frame: At 18 months

    Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).

  3. Difference in Overall Survival Between Lurbinectedin/DOX and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 24 Months

    Time frame: At 24 months

    Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).

  4. Progression-free Survival (PFS) by Independent Review Committee

    Time frame: Every six weeks up to progression disease, a period of approximately 3.5 years

    Progression-free survival (PFS) is defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death). If the patient receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.

  5. Progression-free Survival Rate at 6 Months by Independent Review Committee

    Time frame: At 6 months

    Progression-free survival (PFS) is defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death). If the patient receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.

  6. Progression-free Survival Rate at 12 Months by Independent Review Committee

    Time frame: at 12 months

    Progression-free survival (PFS) is defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death). If the patient receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.

  7. Best Antitumor Response by Independent Review Committee

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1.

    CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown

  8. Overall Response Rate by Independent Review Committee

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1.

    CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown

  9. Duration of Response by Independent Review Committee

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1.

    CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown

  10. Overall Survival in Patients With Chemotherapy-free Interval ≥ 90 Days

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).

  11. Progression-free Survival in Patients With Chemotherapy-free Interval ≥90 Days

    Time frame: Every six weeks up to progression disease, a period of approximately 3.5 years

    Progression-free survival (PFS) is defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death). If the patient receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.

  12. Best Antitumor Response in Patients With Chemotherapy-free Interval ≥ 90 Days

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1.

    CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown

  13. Overall Response Rate in Patients With Chemotherapy-free Interval ≥ 90 Days

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1.

    CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown

  14. Duration of Response in Patients With Chemotherapy-free Interval ≥ 90 Days

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1.

    CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown

  15. Overall Survival in Patients With Chemotherapy-free Interval < 90 Days

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).

  16. Progression-free Survival in Patients With Chemotherapy-free Interval <90 Days

    Time frame: Every six weeks up to progression disease, a period of approximately 3.5 years

    Progression-free survival (PFS) is defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death). If the patient receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.

  17. Best Antitumor Response in Patients With Chemotherapy-free Interval <90 Days

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1.

    CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown

  18. Overall Response Rate in Patients With Chemotherapy-free Interval <90 Days

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1.

    CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown

  19. Duration of Response in Patients With Chemotherapy-free Interval <90 Days

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1.

    CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown

  20. Overall Survival in Patients Without Central Nervous System Involvement at Baseline

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).

  21. Progression-free Survival in Patients Without Central Nervous System Involvement at Baseline

    Time frame: Every six weeks up to progression disease, a period of approximately 3.5 years

    Progression-free survival (PFS) is defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death). If the patient receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.

  22. Best Antitumor Response in Patients Without Central Nervous System Involvement at Baseline

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1.

    CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown

  23. Overall Response Rate in Patients Without Central Nervous System Involvement at Baseline

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1.

    CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown

  24. Duration of Response in Patients Without Central Nervous System Involvement at Baseline

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1.

    CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown

  25. Overall Survival in Patients With Central Nervous System Involvement at Baseline

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).

  26. Progression-free Survival in Patients With Central Nervous System Involvement at Baseline

    Time frame: Every six weeks up to progression disease, a period of approximately 3.5 years

    Progression-free survival (PFS) is defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death). If the patient receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.

  27. Best Antitumor Response in Patients With Central Nervous System Involvement at Baseline

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1.

    CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown

  28. Overall Response Rate in Patients With Central Nervous System Involvement at Baseline

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1.

    CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown

  29. Duration of Response in Patients With Central Nervous System Involvement at Baseline

    Time frame: Every three months up to death or study termination, a period of approximately 3.5 years

    Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1.

    CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown

Sponsors and collaborators

Lead sponsor

PharmaMar

Industry

Registry information

Official study title

Phase III Randomized Clinical Trial of Lurbinectedin (PM01183)/Doxorubicin Versus Cyclophosphamide, Doxorubicin and Vincristine (CAV) or Topotecan as Treatment in Patients With Small-Cell Lung Cancer (SCLC) Who Failed One Prior Platinum-containing Line (ATLANTIS)

Acronym: ATLANTIS

Important dates

Study start
2016
Primary completion
2020
Study completion
2020
First posted
Oct 2, 2015
Registry last updated
Oct 28, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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