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This is a nationwide, multicenter, registry-based prospective cohort study to assess real-world effectiveness of treatment with a pembrolizumab containing regimen in persistent, recurrent, or metastatic cervical cancer. Patients in the observation cohort continue treatment according to standard of care. In the discontinuation cohort, patients discontinue their maintenance treatment with pembrolizumab (with or without discontinuation of bevacizumab). Patients may choose to discontinue pembrolizumab prematurely (with or without discontinuation of bevacizumab) if they achieve a confirmed CR or a confirmed PR to treatment, or on patient's request or due to toxicity. If an eligible patient chooses not to discontinue treatment early they will remain in the observation cohort. The duration of the trial for the individual patient will be until two years from the start of treatment. Survival follow-up will continue for a maximum of 10 years
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Observation cohort | No Intervention | The observation cohort will consist of all participants who receive standard of care treatment and are not eligible for the discontinuation cohort or do not wish to discontinue treatment. Patients will be asked to complete questionnaires every 12 weeks. | |
| Discontinuation cohort | Experimental | The discontinuation cohort will consist of participants who discontinue pembrolizumab (with or without discontinuation of bevacizumab) therapy early according to the inclusion criteria listed in the study protocol. Additionally, will be asked to complete questionnaires every 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Early discontinuation of Pembrolizumab with or without Bevacizumab | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate the progression-free survival (PFS) and compare to the KEYNOTE-826 trial | To evaluate the progression PFS at 12 months and compare it to the historical PFS at 12 months of the KEYNOTE-826 trial. PFS is defined as the time from start of first line treatment to the first documented disease progression or death due to any cause, whichever occurs first. | 12 months; for all patients |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate progression-free survival (PFS) at 12- and 24 months | To evaluate the PFS at 12- and 24 months for the complete cohort; the observation cohort and the discontinuation cohort separately and per the different response outcomes (SD/PR/CR). PFS is defined as the time from start of first line treatment to the first documented disease progression or death due to any cause, whichever occurs first. |
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Inclusion criteria for the observation cohort:
- Persistent, recurrent, or metastatic cervical cancer commencing treatment or currently treated with a pembrolizumab containing regimen.
Inclusion criteria for the early discontinuation cohort:
Previous inclusion in the observation cohort
Choice made to stop pembrolizumab for one of the following reasons:
Eligible and willing to discontinue pembrolizumab (with or without discontinuing bevacizumab)
Exclusion criteria for all cohorts are:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| M. Jalving, MD, PhD | Contact | +31 50 361 2821 | m.jalving@umcg.nl | |
| G. M.M. Lenis, MD | Contact | +31 50 361 6161 | g.m.m.lenis@umcg.nl |
| Name | Affiliation | Role |
|---|---|---|
| M. Jalving | University Medical Center Groningen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Amsterdam UMC | Not yet recruiting | Amsterdam | Netherlands |
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| 12 and 24 months; for all patients |
| To evaluate Overall Survival (OS) | To evaluate the OS, OS is defined as: the time from start of first line treatment to death due to any cause. Survival curves will be plotted, the OS rate at different time points will be estimated using the Kaplan-Meier method and the median OS wil be evaluated. Survival follow-up is for up to ten years after commencement of treatment. To give an indication: median OS in the KEYNOTE-826 trial for CPS≥1 (trial population) cohort was 28.6 months and 24-months OS 53.5%. | From enrollment till the end of survival follow-up of ten years or death. Median OS is estimated to be available at the half of total inclusion period (1,5 of 3 years) + median OS from registration trial, so expected at 56 months from trial start |
| Evaluate objective response rate (ORR) | To evaluate the ORR, ORR is defined as the proportion of patients with CR and PR. Response for the individual patient will be measured/assessed every 12-18 (±1) weeks starting from baseline till two years of treatment, progression or death. | The ORR will be evaluated if all patients have had all response evaluations, this will be estimated at around 5 years (3 year inclusion + 2 year follow-up) after start of study. |
| Evaluate duration of response (DoR) | To evaluate the DoR, which is defined as the time from the first documented evidence of CR or PR until the first documented disease progression or death due to any cause, whichever occurs assesed up to about 48 months since commencement of treatment. | from enrollement till disease progression, follow-up or death assesed up to about 48 months since commencement of treatment. |
| To describe the percentage of patients that develop immune-related endocrinopathies | The percentage of patients that develop immune-related endocrinopathies Ir(S)AEs are collected until end of standard follow-up (2 years or disease progression). | from commencement of treatment to the end of regular follow-up (+/- 48 months) or disease progression. |
| To evaluate the treatment related Immune-Related (Serious) Adverse Events (ir(S)AEs) which led to discontinuation or interruption of systemic treatment. | To describe the percentage of patients which irAEs led to discontinuation or interruption (≥12 weeks) of treatment during (rechallenge of) PD-1 blockade. Ir(S)AEs are collected until end of standard follow-up (2 years or disease progression). | from commencement of treatment to the end of regular follow-up (+/- 48 months) or disease progression. |
| The Health-Related Quality of Life in patients with recurrent, persistent or metastatic cervical cancer treated with a pembrolizumab-containing regimen | The European Organisation For Research And Treatment Of Cancer (EORTC) QLQ-C30. The tool is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status/QoL scale, and six single items. All of the scales and single-item measures range in score from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/QoL represents a high QoL, a high score for a symptom scale/item represents a high level of symptomatology/problems | from enrollment till the end of treatment (two years from commencing treatment), every three months both questionnaires will be sent. |
| The anxiety and depression symptoms in patients with recurrent, persistent or metastatic cervical cancer treated with a pembrolizumab-containing regimen | Hospital Anxiety and Depression Scale (HADS) is designed to assess symptoms of anxiety and depression in clinical and research settings. It consists of 14 items divided into two subscales: anxiety (HADS-A) and depression (HADS-D), each containing seven items scored on a 4-point Likert scale. Scores from 0-21 for each subscale, higher scores means greater distress. | From enrollment till the end of treatment (two years from commencing treatment), every three months both questionnaires will be sent. |
| Antoni van Leeuwenhoek Ziekenhuis | Not yet recruiting | Amsterdam | Netherlands |
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| Catharina Ziekenhuis | Recruiting | Eindhoven | Netherlands |
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| Medisch Spectrum Twente | Not yet recruiting | Enschede | Netherlands |
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| University Mecdical Center Groningen | Recruiting | Groningen | 9713 GZ | Netherlands |
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| LUMC | Recruiting | Leiden | Netherlands |
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| Maastricht UMC | Not yet recruiting | Maastricht | Netherlands |
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| Radboud UMC | Not yet recruiting | Nijmegen | Netherlands |
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| Erasmus MC | Not yet recruiting | Rotterdam | Netherlands |
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| UMC Utrecht | Not yet recruiting | Utrecht | Netherlands |
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| Isala Klinieken | Not yet recruiting | Zwolle | Netherlands |
|
| ID | Term |
|---|---|
| D002583 | Uterine Cervical Neoplasms |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
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| ID | Term |
|---|---|
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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