Ovarian Cancer, Quality of Life, Recurrent Ovarian Carcinoma
Conditions
Keywords
Quality of life, ovarian cancer, platinum sensitive, recurrent
Brief summary
This is a multicenter, randomized, controlled, open-label study including patients with recurrent, platinum-sensitive, ovarian, peritoneal or fallopian tube cancer. The main scope of the trial is to evaluate QoL during chemotherapy comparing trabectedin/PLD with other standard platinum-based chemotherapy in platinum-sensitive disease.
Detailed description
This is a multicenter, randomized, controlled, open-label study including patients with recurrent, platinum-sensitive, ovarian, peritoneal or fallopian tube cancer. The main scope of the trial is to evaluate QoL during chemotherapy comparing trabectedin/PLD with other standard platinum-based chemotherapy in platinum-sensitive disease. Patients with recurrent, platinum-sensitive, ovarian, fallopian tube and peritoneal cancer will be stratified according to surgery for relapse (R0 vs. R1/2 resection) vs. no surgery in the same setting and age (\< 75 years vs. ≥ 75 years), and randomized 1:1 to receive either trabectedin/PLD (Arm A) or one of 3 platinum-based standard therapies without bevacizumab (Arm B, other standard therapy). In case of randomization to other standard therapy, the investigator has the choice between carboplatin/PLD, carboplatin/gemcitabine and carboplatin/paclitaxel. Patients in both treatment arms will receive chemotherapy up for 6 cycles or until disease progression (PD), unacceptable toxicities or patient's wish to stop therapy, whichever occurs first.
Interventions
DRUGTrabectidin (Yondelis)
To compare QoL in patients treated with trabectedin/PLD vs. other standard combination therapy of carboplatin/ PLD, carboplatin/ gemcitabine, or carboplatin/ paclitaxel
Sponsors
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
PharmaMar
North Eastern German Society of Gynaecological Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Women aged ≥ 18 years 2. Patients with histologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal carcinoma or fallopian tube cancer who received ≥1 prior chemotherapy 3. Patients must be eligible for platin-containing therapy; Patient is defined as platin-sensitive when considered for platin-containing therapy by the investigator. The time frame from end of prior therapy until disease progression alone is not pivotal for study participation. Patients without a platin-containing regimen in the previous line who are also eligible for platin-containing regime are also appropriate for participation 4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 5. Adequate baseline organ function as defined as * Leucocytes \> 3.0 x 109/l * Platelet count \> 100 x 109/l * Absolute neutrophil count (ANC) ≥1500/mm3 * Haemoglobin ≥ 9 g/dl * Alkaline Phosphatase (AP) ≤ 2.5 × ULN (consider hepatic isoenzymes 5 nucleotidase or gamma glutamyl transpeptidase (GGT), if the elevation could be osseous in origin) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN * Creatinine-Clearance ≥ 60 ml/min (MDRD formula or Cockroft & Gault formula) * Serum creatinine ≤ 1.5 mg/dl * Creatine phosphokinase (CPK) ≤ 2.5 × ULN * Total bilirubin \< ULN 6. Women of childbearing potential should use contraceptives or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication or be surgically sterile. 7. Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 50% as determined by echocardiogram 8. Patients must provide written informed consent prior to performance of study specific procedures or assessments, and must be willing to comply with treatment and follow up assessments and procedures.
Exclusion criteria
1. Only malignancies, which influence the prognosis 2. Any unstable or serious concurrent condition (e.g. active infection requiring systemic therapy). 3. Chemotherapy or radiation therapy or tumor embolization within 2 weeks prior to the first dose of study drug or planned during study participation. 4. Patients who have refractory disease. Refractory disease is defined if relapse occurs \<4 months after beginning of platin-containing therapy. 5. Hypersensitivity to the active substance or to any of the excipients of study drug 6. Findings from ECG and/or assessment of LVEF which indicate an anthracycline-related cardiotoxic process which contradicts administration of liposomal doxorubicin in accordance with the requirements of the SmPC of PLD. 7. Biological therapy, immunotherapy, hormonal therapy or treatment with an investigational agent within 14 days (for bevacizumab, 30 days) prior to the first dose of study drug. 8. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study 9. Participation in another clinical study with experimental therapy within the 30 days before start of and during treatment. Participation in a non-interventional study should be discussed with sponsor and NC beforehand. 10. Patients in a closed institution according to an authority or court decision (AMG § 40, Abs. 1 No. 4) 11. Patients who are depending on the sponsor/CRO or investigational site as well as on the investigator. 12. Pregnancy or lactation period, or planning to become pregnant within 7 months after the end of treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Quality of Life (QoL) | 12 month (from baseline to end of treatment) | The difference in QoL is defined as change of the mean score of the Trial Outcome Index (TOI) from baseline (TOI at randomization) compared to end of treatment (TOI at EOT) and is calculated as follows: Difference TOI = TOI at EOT - TOI at baseline. 1. equals to 0 meaning no change in quality of life at EOT compared to baseline 2. \>0 meaning a detoriated quality of life at EOT compared to baseline. (The higher the number, the higher the detoriation.) 3. \<0 meaning an improved quality of life at EOT compared to baseline. (The lower the number, the higher the improvement.) TOI is calculated as mean of subscores concerning functional scales (e.g. physical function) and symptomal scales (e.g. body image, chemotherapy side effects, attitude to disease/treatment). Scores of each scale are transformed and ranges between 0-100. High scores for functional scales and symptomal scales meaning a low level of functioning and a high level of symptomatology/problems, respectively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 18 month | Progression-free survival was defined as time (months) from randomization until date of the first occurrence of progression or recurrence, as determined by the investigator using CT criteria, or death from any cause. |
| Overall Survival | through study completion, up to 3 years | Overall survival was defined as time from randomization until date of death to any cause. |
Countries
Germany
Participant flow
Recruitment details
recruitment period:01.02.2018 - 28.03.2023
Pre-assignment details
A total of 204 patients were planned to be randomized. Due to slow recruitment of the trial, the recruitment was prematurely terminated after randomization of the 89th patient.
Participants by arm
| Arm | Count |
|---|---|
| Arm A PLD followed by Trabectedin. Treatment is repeated every 3 weeks for 6 cycles or until disease progression.
Trabectidin (Yondelis): To compare QoL in patients treated with trabectedin/PLD vs. other standard combination therapy of carboplatin/ PLD, carboplatin/ gemcitabine, or carboplatin/ paclitaxel | 44 |
| Arm B * Carboplatin/PLD
* Carboplatin/Gemcitabine
* Carboplatin/Paclitaxel Patients will be treated for 6 cycles or until PD, unacceptable toxicity or patient's wish to discontinue, whichever occurs first.
Trabectidin (Yondelis): To compare QoL in patients treated with trabectedin/PLD vs. other standard combination therapy of carboplatin/ PLD, carboplatin/ gemcitabine, or carboplatin/ paclitaxel | 41 |
| Total | 85 |
Baseline characteristics
| Characteristic | Total | Arm A | Arm B |
|---|---|---|---|
| Age, Continuous | 62.5 years STANDARD_DEVIATION 10.5 | 60.3 years STANDARD_DEVIATION 10.9 | 64.9 years STANDARD_DEVIATION 9.6 |
| Age, Customized < 70 years | 63 Participants | 36 Participants | 27 Participants |
| Age, Customized >= 70 years | 22 Participants | 8 Participants | 14 Participants |
| Body Mass Index (BMI) | 25.7 kg/m² STANDARD_DEVIATION 5.4 | 25.3 kg/m² STANDARD_DEVIATION 5.2 | 26.2 kg/m² STANDARD_DEVIATION 5.5 |
| BRCA mutation Missing | 44 participants | 24 participants | 20 participants |
| BRCA mutation NO | 32 participants | 15 participants | 17 participants |
| BRCA mutation YES | 9 participants | 5 participants | 4 participants |
| ECOG 0 | 30 Participants | 17 Participants | 13 Participants |
| ECOG 1 | 54 Participants | 27 Participants | 27 Participants |
| ECOG 2 | 1 Participants | 0 Participants | 1 Participants |
| ECOG 3 | 0 Participants | 0 Participants | 0 Participants |
| ECOG 4 | 0 Participants | 0 Participants | 0 Participants |
| ECOG 5 | 0 Participants | 0 Participants | 0 Participants |
| Histological grade grade 1 | 2 participants | 2 participants | 0 participants |
| Histological grade grade 2 | 2 participants | 1 participants | 1 participants |
| Histological grade grade 3 | 8 participants | 6 participants | 2 participants |
| Histological grade grade 4 | 0 participants | 0 participants | 0 participants |
| Histological grade Missing | 73 participants | 35 participants | 38 participants |
| Histology of primary tumor Clear cell | 5 participants | 2 participants | 3 participants |
| Histology of primary tumor Mucinous | 1 participants | 0 participants | 1 participants |
| Histology of primary tumor Serous | 79 participants | 42 participants | 37 participants |
| Localization of the primary tumor Primary ovarian carcinoma | 71 participants | 37 participants | 34 participants |
| Localization of the primary tumor Primary peritoneal carcinoma | 7 participants | 3 participants | 4 participants |
| Localization of the primary tumor Tube carcinoma | 7 participants | 4 participants | 3 participants |
| Metastasis staging (according to TNM staging system) M0 | 41 participants | 23 participants | 18 participants |
| Metastasis staging (according to TNM staging system) M1 | 43 participants | 20 participants | 23 participants |
| Metastasis staging (according to TNM staging system) Missing | 1 participants | 1 participants | 0 participants |
| Number of previous chemotherapies 1 | 68 participants | 32 participants | 36 participants |
| Number of previous chemotherapies 2 | 12 participants | 10 participants | 2 participants |
| Number of previous chemotherapies 3 | 4 participants | 1 participants | 3 participants |
| Number of previous chemotherapies 7 | 1 participants | 1 participants | 0 participants |
| Number of relapses after previous therapy 1 | 67 participants | 32 participants | 35 participants |
| Number of relapses after previous therapy 2 | 12 participants | 9 participants | 3 participants |
| Number of relapses after previous therapy 3 | 5 participants | 2 participants | 3 participants |
| Number of relapses after previous therapy 7 | 1 participants | 1 participants | 0 participants |
| Patient received at least one maintenance therapy with PARPi | 14 participants | 10 participants | 4 participants |
| Race and Ethnicity Not Collected | 0 Participants | — | — |
| Sex: Female, Male Female | 85 Participants | 44 Participants | 41 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 40 / 44 | 38 / 41 |
| other Total, other adverse events | 40 / 44 | 41 / 41 |
| serious Total, serious adverse events | 20 / 44 | 17 / 41 |
Outcome results
Primary
Difference in Quality of Life (QoL)
The difference in QoL is defined as change of the mean score of the Trial Outcome Index (TOI) from baseline (TOI at randomization) compared to end of treatment (TOI at EOT) and is calculated as follows: Difference TOI = TOI at EOT - TOI at baseline. 1. equals to 0 meaning no change in quality of life at EOT compared to baseline 2. \>0 meaning a detoriated quality of life at EOT compared to baseline. (The higher the number, the higher the detoriation.) 3. \<0 meaning an improved quality of life at EOT compared to baseline. (The lower the number, the higher the improvement.) TOI is calculated as mean of subscores concerning functional scales (e.g. physical function) and symptomal scales (e.g. body image, chemotherapy side effects, attitude to disease/treatment). Scores of each scale are transformed and ranges between 0-100. High scores for functional scales and symptomal scales meaning a low level of functioning and a high level of symptomatology/problems, respectively.
Time frame: 12 month (from baseline to end of treatment)
Population: Five patients were excluded from the PP (per protocol) population due to violation of inclusion criteria.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A | Difference in Quality of Life (QoL) | TOI at randomization (baseline) | 31.1 units on a scale | Standard Deviation 15.6 |
| Arm A | Difference in Quality of Life (QoL) | TOI at EOT | 36.9 units on a scale | Standard Deviation 18.1 |
| Arm A | Difference in Quality of Life (QoL) | Difference TOI: randomization over EOT | 6.5 units on a scale | Standard Deviation 12.8 |
| Arm B | Difference in Quality of Life (QoL) | TOI at randomization (baseline) | 28.7 units on a scale | Standard Deviation 14.7 |
| Arm B | Difference in Quality of Life (QoL) | TOI at EOT | 34.4 units on a scale | Standard Deviation 16.6 |
| Arm B | Difference in Quality of Life (QoL) | Difference TOI: randomization over EOT | 5.5 units on a scale | Standard Deviation 12.7 |
Secondary
Overall Survival
Overall survival was defined as time from randomization until date of death to any cause.
Time frame: through study completion, up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Overall Survival | 14.9 months |
| Arm B | Overall Survival | 19.9 months |
Secondary
Progression-free Survival
Progression-free survival was defined as time (months) from randomization until date of the first occurrence of progression or recurrence, as determined by the investigator using CT criteria, or death from any cause.
Time frame: 18 month
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Progression-free Survival | 8.2 months |
| Arm B | Progression-free Survival | 11 months |