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JOURNAL ONKOLOGIE – STUDIE
PERCEPTION

Study of Pembrolizumab Combination With Chemotherapy in Platinum-sensitive Recurrent Low-grade Serous Ovarian Cancer

Rekrutierend

NCT-Nummer:
NCT04575961

Studienbeginn:
Februar 2022

Letztes Update:
09.11.2023

Wirkstoff:
Pembrolizumab

Indikation (Clinical Trials):
Carcinoma, Ovarian Neoplasms, Carcinoma, Ovarian Epithelial, Fallopian Tube Neoplasms, Cystadenocarcinoma, Serous, Hypersensitivity

Geschlecht:
Frauen

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
North Eastern German Society of Gynaecological Oncology

Collaborator:
Merck Sharp & Dohme LLC

Kontakt

Studienlocations
(2 von 2)

Studien-Informationen

Detailed Description:

In this study, we will evaluate efficacy and safety of pembrolizumab in combination with

chemotherapy (physician's choice) in subjects with low-grade ovarian cancer.

Patients will receive Pembrolizumab 200mg q3w until progression or unacceptable toxicity, for

a maximum of 35 cycles PLUS one of the following standard chemotherapies for LGSOC

(investigators' choice):

Carboplatin AUC 4 + Gemcitabine 1000mg/m² (q3w for 3-6 cycles) or Carboplatin AUC 5 +

pegylated liposomal Doxorubicin 30mg/m² (q4w for 3-6 cycles). As primary objective 12-month

progression free survival (PFS) rate will be analysed.

About 2 sites in Germany will participate in this study to recruit 33 patients in 24 months.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Female, age at least 18 years.

- Histologically diagnosed low-grade serous ovarian cancer, fallopian tube cancer, or

primary peritoneal cancer.

- Patients must have completed at least 1 previous course of platinum-containing therapy

(e.g., combination with carboplatin or cisplatin. Maintenance therapy with bevacizumab

and/or endocrine agents is allowed).

- Progression or recurrence after platinum-containing therapy, occurring no sooner than

6 months after completion of the last dose of platinum chemotherapy (platinum

sensitive disease).

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

- Women of childbearing potential should not become pregnant while on the Product and

should not be pregnant at the beginning of treatment. A pregnancy test should be

performed on all women of childbearing potential prior to receiving the Product. Women

of childbearing potential must agree to follow contraceptive guidance during the

treatment period and for 6 months after receiving the last dose of the study therapy.

- The participant (or legally acceptable representative if applicable) provides written

informed consent for the trial.

- Availability of archival tumor tissue sample or newly obtained core or excisional

biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded

(FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to

archived tissue.

Exclusion Criteria:

- High-grade ovarian cancer.

- Persistent ≥Grade 2 hematologic toxicity from prior cancer therapy Note: Participants

must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline.

Participants with ≤Grade 2 neuropathy may be eligible.

Note: If participant received major surgery, they must have recovered adequately from the

toxicity and/or complications from the intervention prior to starting study treatment.

- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with

an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,

CTLA-4, OX 40, CD137).

- Is eligible for carboplatin-based doublet therapy in combination with bevacizumab in

the relapse situation, since no treatment with bevacizumab has been administered in

the first line therapy.

- Has received prior systemic anti-cancer therapy including investigational agents

within 4 weeks.

- Has received prior radiotherapy within 2 weeks of start of study treatment.

Participants must have recovered from all radiation-related toxicities, not require

corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted

for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.

- Has received a live vaccine within 30 days prior to the first dose of study drug.

Examples of live vaccines include, but are not limited to, the following: measles,

mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus

Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection

are generally killed virus vaccines and are allowed; however, intranasal influenza

vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.

- Is currently participating in or has participated in a study of an investigational

agent or has used an investigational device within 4 weeks prior to the first dose of

study treatment.

Note: Participants who have entered the follow-up phase of an investigational study may

participate as long as it has been 4 weeks after the last dose of the previous

investigational agent.

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy

(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of

immunosuppressive therapy within 7 days prior to the first dose of study drug.

- Has a known additional malignancy that is progressing or has required active treatment

within the past 3 years. Note: Participants with basal cell carcinoma of the skin,

squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma,

cervical cancer in situ) that have undergone potentially curative therapy are not

excluded.

- Has known active CNS metastases and/or carcinomatous meningitis. Participants with

previously treated brain metastases may participate provided they are radiologically

stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging

(note that the repeat imaging should be performed during study screening), clinically

stable and without requirement of steroid treatment for at least 14 days prior to

first dose of study treatment.

- Has a bleeding tumor

- Has hypersensitivity to any of the study drugs the patient will be treated with and/or

to any of the excipients of the study drugs the patient will be treated with.

- Has active autoimmune disease that has required systemic treatment in the past 2 years

(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive

drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid

replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a

form of systemic treatment.

- Has a history of (non-infectious) pneumonitis that required steroids or has current

pneumonitis.

- Has an active infection requiring systemic therapy.

- Has a known history of Human Immunodeficiency Virus (HIV).

- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]

reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] has been

detected) infection.

- Has a known history of active TB (Bacillus Tuberculosis).

- Has a history or current evidence of any condition, therapy, or laboratory abnormality

that might confound the results of the study, interfere with the subject's

participation for the full duration of the study, or is not in the best interest of

the subject to participate, in the opinion of the treating investigator.

- Has had an allogenic tissue/ solid organ transplant.

- Has known psychiatric or substance abuse disorders that would interfere with

cooperation with the requirements of the trial.

- Is pregnant or breastfeeding, or expecting to conceive within the projected duration

of the study, starting with the screening visit through 6 months after the last dose

of trial treatment.

- Patients unable to be regularly followed for any reason (geographic, familiar, social,

psychologic, housed in an institution e.g. prison because of a court agreement or

administrative order).

- Subjects that are depending on the sponsor/CRO or investigational site as well as on

the investigator.

Studien-Rationale

Primary outcome:

1. 12-month (48 weeks) progression free survival (PFS) rate (Time Frame - 12 month):
The primary objective of this clinical trial is 12-month Progression Free Survival (PFS) rate after start of treatment. Tumor progression will be assessed with local imaging per irRECIST 1.1 and is defined according to RECIST criteria. Start of therapy will be counted when the patient receives the first dose of pembrolizumab.



Secondary outcome:

1. Response rate (SD, PR or CR) after 6, 12, 18 and 24 months (Time Frame - 6, 12, 18 and 24 months):
Stable Disease, Partial Response or CR will be evaluated per irRECIST 1.1 after 6, 12,18 and 24 months

2. Ki-67 (Time Frame - 24 month):
Marker of proliferation Ki-67 Obtain archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for routine determination of PD-1, PD-L1 and Ki-67 status

3. Time of next medical intervention (Time Frame - 24 month):
Time of next medical intervention due to tumor progress

4. Quality of life until 6 months after progress (Time Frame - 6 month):
Patients are asked to answer the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). Responses of questions 1-28 are based on a 4-point scale (1=not at all; 4=Very much), with a higher score indicating a high degree of symptomatology and must therefore be assessed negatively. Responses of questions 29 and 30 are based on a 7-point scale (1=Very poor; 7=Excellent), with a higher score indicating a better global health status.

5. TFST and response to first subsequent treatment (Time Frame - 24 month):
Time to first subsequent treatment and response to first subsequent treatment will be evaluated.

6. Safety Endpoints - safety of combination therapy (ctx and pembrolizumab) according to CTCAE 5.0 criteria will be used as endpoint (Time Frame - 24 month):
The safety objective is to characterize the safety and tolerability of pembrolizumab in combination with chemotherapy in subjects with advanced low grade ovarian cancer. The following safety parameters will be analyzed: adverse events and serious adverse events graded per NCI CTCAE, Version 4.0 criteria with time to onset/recovery, causality and outcome; changes in laboratory values, vital signs since baseline, treatment discontinuations and reason for discontinuation, death and cause of death etc. concomitant medications will be collected with time and reasons of use. These are routine safety parameters collected and analyzed in Phase II /III oncology trials. Furthermore, specific immune-related adverse events (irAEs) will be collected

7. PFS (time-to-event) and PFS rate after 6, 12, 18 and 24 months (Time Frame - 6, 12, 18 and 24 months):
Progression Free Survival (time to event) and PFS rate after 6, 12, 18 and 24 months after start of treatment. Tumor progression will be assessed with local imaging per irRECIST 1.1 and is defined according to RECIST criteria. Start of therapy will be counted when the patient receives the first dose of pembrolizumab

8. Quality of life 2 until 6 months after progress (Time Frame - 6 month):
Patients are asked to answer the EORTC QoL Questionnaire-Ovarian Cancer (QLQ-OV28). Responses are based on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating better symptoms.

Geprüfte Regime

  • Pembrolizumab (Keytruda):
    Participants receive pembrolizumab 200 mg by intravenous (IV) infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles

Quelle: ClinicalTrials.gov


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