Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02566993
Recruitment Status : Completed
First Posted : October 2, 2015
Results First Posted : October 28, 2021
Last Update Posted : October 28, 2021
Sponsor:
Information provided by (Responsible Party):
PharmaMar

Brief 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.

Condition or disease Intervention/treatment Phase
Small-cell Lung Cancer Drug: Lurbinectedin (PM01183) Drug: Doxorubicin (DOX) Drug: Cyclophosphamide (CTX) Drug: Vincristine (VCR) Drug: Topotecan Phase 3

Detailed Description:
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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 613 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : August 30, 2016
Actual Primary Completion Date : February 24, 2020
Actual Study Completion Date : February 24, 2020


Arm Intervention/treatment
Experimental: Experimental Arm
Lurbinectedin (PM01183) / Doxorubicin
Drug: Lurbinectedin (PM01183)
Drug: Doxorubicin (DOX)
Active Comparator: Control Arm 1
CAV (Cyclophosphamide (CTX), Doxorubicin (DOX) and Vincristine (VCR))
Drug: Doxorubicin (DOX)
Drug: Cyclophosphamide (CTX)
Drug: Vincristine (VCR)
Active Comparator: Control Arm 2
Topotecan
Drug: Topotecan



Primary Outcome Measures :
  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 Outcome Measures :
  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




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02566993


Locations
Show Show 160 study locations
Sponsors and Collaborators
PharmaMar
  Study Documents (Full-Text)

Documents provided by PharmaMar:
Study Protocol  [PDF] May 3, 2018
Statistical Analysis Plan  [PDF] September 4, 2020

Layout table for additonal information
Responsible Party: PharmaMar
ClinicalTrials.gov Identifier: NCT02566993    
Other Study ID Numbers: PM1183-C-003-14
First Posted: October 2, 2015    Key Record Dates
Results First Posted: October 28, 2021
Last Update Posted: October 28, 2021
Last Verified: August 2021
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Cyclophosphamide
Doxorubicin
Vincristine
Topotecan
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents