Ovarian Cancer
Conditions
Brief summary
Multicenter, open-label, randomized, controlled phase III clinical trial to evaluate the activity and safety of PM01183 versus PLD or topotecan as control arm in patients with platinum-resistant ovarian cancer. PM01183 will be explored as single agent in the experimental arm (Arm A) versus PLD or topotecan in the control arm (Arm B).
Interventions
Sponsors
PharmaMar
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>/= 18 years * Confirmed diagnosis of unresectable epithelial ovarian, fallopian tube or primary peritoneal cancer. * Platinum-resistant disease (PFI: 1-6 months after last platinum-containing chemotherapy). * Evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 criteria * No more than three prior systemic chemotherapy regimens * Eastern Cooperative Oncology Group (ECOG) performance status (PS) (ECOG PS) ≤ 2 * Adequate hematological, renal, metabolic and hepatic function
Exclusion criteria
* Concomitant diseases/conditions: cardiac disease, immunodeficiency, chronic active hepatitis or cirrhosis, uncontrolled infection, bowel obstruction, any other major illness * Prior treatment with PM01183, trabectedin, or with both PLD and topotecan. * Requirement of permanent or frequent (i.e., once per week) external drainages within two weeks prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival by Independent Review Committee | Time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation, whichever came first, assessed up to 3 years | The primary endpoint was PFS by IRC assessment, 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 received further antitumor therapy or was lost to follow-up before PD, PFS was censored at the date of last tumor assessment before the date of subsequent antitumor treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From the date of randomization to the date of death or last contact, up to 12 months after last patient inclusion, for a maximum of up to 3 years | Calculated from the date of randomization to the date of death (death event) or last contact (in this case, survival was censored on that date). |
| Overall Response Rate (ORR) by Independent Review Committee | At baseline and every eight weeks from randomization until evidence of PD, assessed up to 3 years | Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments. Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method \[computed tomography scan or magnetic resonance imaging\]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum; Overall Response (OR)=CR+PR. |
| Overall Response Rate by Investigator's Assessment | At baseline and every eight weeks from randomization until evidence of PD, assessed up to 3 years | Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments. Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method \[computed tomography scan or magnetic resonance imaging\]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum; Overall Response (OR)=CR+PR. |
| Progression-free Survival by Investigator's Assessment | Time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation, whichever came first, assessed up to 3 years | The primary endpoint was PFS by Investigator's Assessment, 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 received further antitumor therapy or was lost to follow-up before PD, PFS was censored at the date of last tumor assessment before the date of subsequent antitumor treatment. |
| Duration of Response by Investigator's Assessment | The time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented, up to 3 years | Duration of response (DR): calculated from the date of first documentation of response per RECIST v.1.1 (CR or PR, whichever came first) to the date of documented PD or death. The censoring rules defined above for PFS were used for duration of response. Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments. Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method \[computed tomography scan or magnetic resonance imaging\]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR. |
| Best Response According to Tumor Marker Evaluation (CA-125) | At baseline and every eight weeks from randomization until evidence of PD, up to 3 years | Best response according to tumor marker evaluation (CA-125): defined as the best response obtained according to GCIG criteria. Tumor marker assessments were performed at baseline and every eight weeks from randomization until evidence of PD. Progression based on serum CA-125 levels was defined on the basis of a progressive serial elevation of serum CA-125 according to: A. Patients with elevated CA-125 pretreatment and normalization of CA-125 must show evidence of CA-125 greater than, or equal to, 2 times the upper limit of the reference range on 2 occasions at least 1 week apart or B. Patients with elevated CA-125 before treatment, which never normalizes, must show evidence of CA-125 greater than, or equal to, 2 times the nadir value on 2 occasions at least 1 week apart or C. Patients with CA-125 in the reference range before treatment must show evidence of CA-125 greater than, or equal to, 2 times the upper limit of the reference range on 2 occasions at least 1 week apart. |
| Duration of Response by Independent Review Committee | The time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented, up to 3 years | Duration of response (DR): calculated from the date of first documentation of response per RECIST v.1.1 (CR or PR, whichever came first) to the date of documented PD or death. The censoring rules defined above for PFS were used for duration of response. Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments. Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method \[computed tomography scan or magnetic resonance imaging\]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR. |
Countries
United States
Participant flow
Recruitment details
First randomization/first study treatment administration took place on 26JUN2015. The cutoff date for results was 12OCT2018. 534 patients were screened; 442 were randomized at 83 sites/12 countries. 10 patients did not receive the study treatment.
Pre-assignment details
IC;Age≥18 years;confirmed diagnosis of unresectable epithelial ovarian, fallopian tube or primary peritoneal cancer;Platinum-resistant disease;ECOG PS≤2;Adequate hematological, renal, metabolic, and hepatic function
Participants by arm
| Arm | Count |
|---|---|
| Lurbinectedin 3.2 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks = one treatment cycle) through peripheral or central lines. A minimum total volume of 100 mL, diluted in 5% glucose or 0.9% sodium chloride solution for infusion, had to be used for administration through a central venous catheter; if a peripheral venous catheter was used, the minimum volume was 250 mL | 221 |
| Control (PLD or Topotecan) Patients randomized to the Control arm were assigned to receive PLD if they had previously been treated with topotecan, or to receive topotecan if they had previously been treated with PLD. However, if the number of patients randomized to either PLD or topotecan reached 60% (i.e., 126 patients) of the total number of patients expected in the Control Arm, then the treatment of choice in the Control Arm would be restricted to the less frequent control drug until the end of accrual | 221 |
| Total | 442 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 11 | 3 |
| Overall Study | Non-treatment-related AE | 8 | 8 |
| Overall Study | Not treated | 2 | 8 |
| Overall Study | Other reason not specified | 3 | 1 |
| Overall Study | Physician Decision | 8 | 17 |
| Overall Study | Progressive disease | 152 | 135 |
| Overall Study | Symptomatic deterioration | 13 | 19 |
| Overall Study | Treatment-related AE | 10 | 14 |
| Overall Study | Withdrawal by Subject | 14 | 16 |
Baseline characteristics
| Characteristic | Control (PLD or Topotecan) | Lurbinectedin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 80 Participants | 95 Participants | 175 Participants |
| Age, Categorical Between 18 and 65 years | 141 Participants | 126 Participants | 267 Participants |
| Age, Continuous | 59.0 years | 63.0 years | 61.0 years |
| Body mass index 20-25 kg/m^2 | 84 Participants | 82 Participants | 166 Participants |
| Body mass index ≤20 kg/m^2 | 37 Participants | 26 Participants | 63 Participants |
| Body mass index 25-30 kg/m^2 | 51 Participants | 62 Participants | 113 Participants |
| Body mass index >30 kg/m^2 | 49 Participants | 50 Participants | 99 Participants |
| Body mass index Unknown | 0 Participants | 1 Participants | 1 Participants |
| Body mass index | 24.7 kg/m^2 | 25.1 kg/m^2 | 24.9 kg/m^2 |
| Body Surface Area | 1.7 m^2 | 1.7 m^2 | 1.7 m^2 |
| BRCA status BRCA1 | 8 Participants | 10 Participants | 18 Participants |
| BRCA status BRCA2 | 3 Participants | 4 Participants | 7 Participants |
| BRCA status Not mutated | 61 Participants | 64 Participants | 125 Participants |
| BRCA status Unknown | 149 Participants | 143 Participants | 292 Participants |
| Clinically evident ascites No | 182 Participants | 186 Participants | 368 Participants |
| Clinically evident ascites Yes | 39 Participants | 35 Participants | 74 Participants |
| ECOG PS PS 0 | 123 Participants | 126 Participants | 249 Participants |
| ECOG PS PS 1 | 94 Participants | 87 Participants | 181 Participants |
| ECOG PS PS 2 | 4 Participants | 8 Participants | 12 Participants |
| First diagnosis to randomization | 20.7 months | 23.4 months | 22.05 months |
| Height | 161.0 cm | 161.0 cm | 161.0 cm |
| Histologic grade Moderately differentiated | 24 Participants | 21 Participants | 45 Participants |
| Histologic grade Poorly differentiated/Undifferentiated | 143 Participants | 154 Participants | 297 Participants |
| Histologic grade Unknown | 39 Participants | 30 Participants | 69 Participants |
| Histologic grade Well differentiated | 15 Participants | 16 Participants | 31 Participants |
| Histology type Clear cell | 12 Participants | 10 Participants | 22 Participants |
| Histology type Endometrioid | 6 Participants | 14 Participants | 20 Participants |
| Histology type Mucinous | 1 Participants | 3 Participants | 4 Participants |
| Histology type Other | 3 Participants | 13 Participants | 16 Participants |
| Histology type Serous/Papillary | 199 Participants | 181 Participants | 380 Participants |
| Intestinal sub-occlusion No | 211 Participants | 212 Participants | 423 Participants |
| Intestinal sub-occlusion Yes | 10 Participants | 9 Participants | 19 Participants |
| Other prior surgical procedures No | 140 Participants | 135 Participants | 275 Participants |
| Other prior surgical procedures Yes | 81 Participants | 86 Participants | 167 Participants |
| Primary site Fallopian | 13 Participants | 11 Participants | 24 Participants |
| Primary site Ovarian | 195 Participants | 196 Participants | 391 Participants |
| Primary site Peritoneal | 13 Participants | 14 Participants | 27 Participants |
| Prior Cytoreductive surgery No | 17 Participants | 23 Participants | 40 Participants |
| Prior Cytoreductive surgery Yes | 204 Participants | 198 Participants | 402 Participants |
| Prior radiotherapy No | 216 Participants | 215 Participants | 431 Participants |
| Prior radiotherapy Yes | 5 Participants | 6 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants | 21 Participants | 35 Participants |
| Race (NIH/OMB) White | 201 Participants | 192 Participants | 393 Participants |
| Radiological presence of ascites No | 150 Participants | 162 Participants | 312 Participants |
| Radiological presence of ascites Yes | 71 Participants | 59 Participants | 130 Participants |
| Region of Enrollment Austria | 4 participants | 3 participants | 7 participants |
| Region of Enrollment Belgium | 19 participants | 21 participants | 40 participants |
| Region of Enrollment Bulgaria | 5 participants | 5 participants | 10 participants |
| Region of Enrollment Czechia | 5 participants | 5 participants | 10 participants |
| Region of Enrollment France | 12 participants | 19 participants | 31 participants |
| Region of Enrollment Hungary | 14 participants | 9 participants | 23 participants |
| Region of Enrollment Italy | 47 participants | 47 participants | 94 participants |
| Region of Enrollment Romania | 11 participants | 11 participants | 22 participants |
| Region of Enrollment Serbia | 4 participants | 5 participants | 9 participants |
| Region of Enrollment Spain | 46 participants | 40 participants | 86 participants |
| Region of Enrollment United Kingdom | 14 participants | 17 participants | 31 participants |
| Region of Enrollment United States | 40 participants | 39 participants | 79 participants |
| Sex: Female, Male Female | 221 Participants | 221 Participants | 442 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Sites involved | 2.0 number of sites | 2.0 number of sites | 2.0 number of sites |
| Weight | 63.0 Kg | 65.8 Kg | 64.4 Kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 170 / 219 | 171 / 213 |
| other Total, other adverse events | 212 / 219 | 211 / 213 |
| serious Total, serious adverse events | 92 / 219 | 85 / 213 |
Outcome results
Primary
Progression-free Survival by Independent Review Committee
The primary endpoint was PFS by IRC assessment, 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 received further antitumor therapy or was lost to follow-up before PD, PFS was censored at the date of last tumor assessment before the date of subsequent antitumor treatment.
Time frame: Time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation, whichever came first, assessed up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin | Progression-free Survival by Independent Review Committee | 3.5 months |
| Control (PLD or Topotecan) | Progression-free Survival by Independent Review Committee | 3.6 months |
Comparison: PFS between treatmentsp-value: 0.629495% CI: [0.854, 1.309]Log Rank
Comparison: PFS (%) at 6 months95% CI: [18.4, 30.7]
Comparison: PFS (%) at 6 months95% CI: [20.9, 34.4]
Comparison: PFS (%) at 6 months between treatmentsp-value: 0.5032Normal approximation
Comparison: PFS (%) at 12 months95% CI: [4.7, 13.3]
Comparison: PFS (%) at 12 months95% CI: [3.3, 12.5]
Comparison: PFS (%) at 12 months between treatmentsp-value: 0.6742Normal approximation
Secondary
Best Response According to Tumor Marker Evaluation (CA-125)
Best response according to tumor marker evaluation (CA-125): defined as the best response obtained according to GCIG criteria. Tumor marker assessments were performed at baseline and every eight weeks from randomization until evidence of PD. Progression based on serum CA-125 levels was defined on the basis of a progressive serial elevation of serum CA-125 according to: A. Patients with elevated CA-125 pretreatment and normalization of CA-125 must show evidence of CA-125 greater than, or equal to, 2 times the upper limit of the reference range on 2 occasions at least 1 week apart or B. Patients with elevated CA-125 before treatment, which never normalizes, must show evidence of CA-125 greater than, or equal to, 2 times the nadir value on 2 occasions at least 1 week apart or C. Patients with CA-125 in the reference range before treatment must show evidence of CA-125 greater than, or equal to, 2 times the upper limit of the reference range on 2 occasions at least 1 week apart.
Time frame: At baseline and every eight weeks from randomization until evidence of PD, up to 3 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lurbinectedin | Best Response According to Tumor Marker Evaluation (CA-125) | Partial response | 33 Participants |
| Lurbinectedin | Best Response According to Tumor Marker Evaluation (CA-125) | Progressive disease | 17 Participants |
| Lurbinectedin | Best Response According to Tumor Marker Evaluation (CA-125) | Stable disease | 95 Participants |
| Lurbinectedin | Best Response According to Tumor Marker Evaluation (CA-125) | Unknown | 15 Participants |
| Lurbinectedin | Best Response According to Tumor Marker Evaluation (CA-125) | Complete response | 13 Participants |
| Control (PLD or Topotecan) | Best Response According to Tumor Marker Evaluation (CA-125) | Unknown | 23 Participants |
| Control (PLD or Topotecan) | Best Response According to Tumor Marker Evaluation (CA-125) | Complete response | 3 Participants |
| Control (PLD or Topotecan) | Best Response According to Tumor Marker Evaluation (CA-125) | Partial response | 29 Participants |
| Control (PLD or Topotecan) | Best Response According to Tumor Marker Evaluation (CA-125) | Stable disease | 94 Participants |
| Control (PLD or Topotecan) | Best Response According to Tumor Marker Evaluation (CA-125) | Progressive disease | 16 Participants |
Comparison: ORR (%) by CA-12595% CI: [20.2, 33.8]
Comparison: ORR (%) by CA-12595% CI: [13.7, 26.3]
Comparison: ORR (%) by CA-125 between treatmentsp-value: 0.1231Fisher Exact
Secondary
Duration of Response by Independent Review Committee
Duration of response (DR): calculated from the date of first documentation of response per RECIST v.1.1 (CR or PR, whichever came first) to the date of documented PD or death. The censoring rules defined above for PFS were used for duration of response. Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments. Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method \[computed tomography scan or magnetic resonance imaging\]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR.
Time frame: The time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented, up to 3 years
Population: Patients who have CR or PR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin | Duration of Response by Independent Review Committee | 4.0 months |
| Control (PLD or Topotecan) | Duration of Response by Independent Review Committee | 3.7 months |
Comparison: Duration of response between treatmentsp-value: 0.263195% CI: [0.769, 2.569]Log Rank
Secondary
Duration of Response by Investigator's Assessment
Duration of response (DR): calculated from the date of first documentation of response per RECIST v.1.1 (CR or PR, whichever came first) to the date of documented PD or death. The censoring rules defined above for PFS were used for duration of response. Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments. Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method \[computed tomography scan or magnetic resonance imaging\]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR.
Time frame: The time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented, up to 3 years
Population: Patients who have CR or PR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin | Duration of Response by Investigator's Assessment | 4.3 months |
| Control (PLD or Topotecan) | Duration of Response by Investigator's Assessment | 3.7 months |
p-value: 0.827695% CI: [0.64, 1.743]Log Rank
Secondary
Overall Response Rate by Investigator's Assessment
Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments. Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method \[computed tomography scan or magnetic resonance imaging\]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum; Overall Response (OR)=CR+PR.
Time frame: At baseline and every eight weeks from randomization until evidence of PD, assessed up to 3 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lurbinectedin | Overall Response Rate by Investigator's Assessment | Partial response | 32 Participants |
| Lurbinectedin | Overall Response Rate by Investigator's Assessment | Progressive disease | 63 Participants |
| Lurbinectedin | Overall Response Rate by Investigator's Assessment | Stable disease | 107 Participants |
| Lurbinectedin | Overall Response Rate by Investigator's Assessment | Unknown | 16 Participants |
| Lurbinectedin | Overall Response Rate by Investigator's Assessment | Complete response | 3 Participants |
| Control (PLD or Topotecan) | Overall Response Rate by Investigator's Assessment | Unknown | 22 Participants |
| Control (PLD or Topotecan) | Overall Response Rate by Investigator's Assessment | Complete response | 2 Participants |
| Control (PLD or Topotecan) | Overall Response Rate by Investigator's Assessment | Partial response | 35 Participants |
| Control (PLD or Topotecan) | Overall Response Rate by Investigator's Assessment | Stable disease | 94 Participants |
| Control (PLD or Topotecan) | Overall Response Rate by Investigator's Assessment | Progressive disease | 68 Participants |
Comparison: Overall response rate (ORR)95% CI: [11.3, 21.3]
Comparison: Overall response rate (ORR)95% CI: [12.1, 22.3]
Comparison: Overall response rate (ORR) between treatmentsp-value: 0.8976Fisher Exact
Secondary
Overall Response Rate (ORR) by Independent Review Committee
Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments. Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method \[computed tomography scan or magnetic resonance imaging\]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum; Overall Response (OR)=CR+PR.
Time frame: At baseline and every eight weeks from randomization until evidence of PD, assessed up to 3 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lurbinectedin | Overall Response Rate (ORR) by Independent Review Committee | Partial response | 29 Participants |
| Lurbinectedin | Overall Response Rate (ORR) by Independent Review Committee | Progressive disease | 83 Participants |
| Lurbinectedin | Overall Response Rate (ORR) by Independent Review Committee | Stable disease | 90 Participants |
| Lurbinectedin | Overall Response Rate (ORR) by Independent Review Committee | Unknown | 16 Participants |
| Lurbinectedin | Overall Response Rate (ORR) by Independent Review Committee | Complete response | 3 Participants |
| Control (PLD or Topotecan) | Overall Response Rate (ORR) by Independent Review Committee | Unknown | 24 Participants |
| Control (PLD or Topotecan) | Overall Response Rate (ORR) by Independent Review Committee | Complete response | 3 Participants |
| Control (PLD or Topotecan) | Overall Response Rate (ORR) by Independent Review Committee | Partial response | 25 Participants |
| Control (PLD or Topotecan) | Overall Response Rate (ORR) by Independent Review Committee | Stable disease | 97 Participants |
| Control (PLD or Topotecan) | Overall Response Rate (ORR) by Independent Review Committee | Progressive disease | 72 Participants |
Comparison: Overall response rate95% CI: [10.1, 19.8]
Comparison: Overall response rate95% CI: [8.6, 17.8]
Comparison: Overall response rate between treatmentsp-value: 0.6772Fisher Exact
Secondary
Overall Survival (OS)
Calculated from the date of randomization to the date of death (death event) or last contact (in this case, survival was censored on that date).
Time frame: From the date of randomization to the date of death or last contact, up to 12 months after last patient inclusion, for a maximum of up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin | Overall Survival (OS) | 11.4 months |
| Control (PLD or Topotecan) | Overall Survival (OS) | 10.9 months |
Comparison: OS between treatmentsp-value: 0.802195% CI: [0.772, 1.183]Log Rank
Comparison: OS (%) at 12 months95% CI: [41.3, 54.8]
Comparison: OS (%) at 12 months95% CI: [38.4, 52]
Comparison: OS (%) at 12 months between treatmentsp-value: 0.5515Normal approximation
Comparison: OS (%) at 24 months95% CI: [16.8, 28.2]
Comparison: OS (%) at 24 months95% CI: [17.1, 28.7]
Comparison: OS (%) at 24 months between treatmentsp-value: 0.9253Normal approximation
Secondary
Progression-free Survival by Investigator's Assessment
The primary endpoint was PFS by Investigator's Assessment, 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 received further antitumor therapy or was lost to follow-up before PD, PFS was censored at the date of last tumor assessment before the date of subsequent antitumor treatment.
Time frame: Time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation, whichever came first, assessed up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin | Progression-free Survival by Investigator's Assessment | 3.7 months |
| Control (PLD or Topotecan) | Progression-free Survival by Investigator's Assessment | 3.7 months |
Comparison: PFS between treatmentsp-value: 0.767395% CI: [0.805, 1.209]Log Rank
Comparison: PFS (%) at 6 months95% CI: [22.8, 35.4]
Comparison: PFS (%) at 6 months95% CI: [21.3, 33.9]
Comparison: PFS (%) at 6 months between treatmentsp-value: 0.7385Normal approximation
Comparison: PFS (%) at 12 months95% CI: [4.8, 12.7]
Comparison: PFS (%) at 12 months95% CI: [4.2, 12.2]
Comparison: PFS (%) at 12 months between treatmentsp-value: 0.8245Normal approximation