Perception

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Nord-Ostdeutsche Gesellschaft Fuer Gynaekologische Onkologie e.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Jan 2022 → ongoing

Decision date (initial)

2024-02-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-508155-40-00

EudraCT number

2020-004083-25

ClinicalTrials.gov

NCT04575961

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

This trial aims to confirm that pembrolizumab is effective in low grade serous ovarian cancer patients. The primary objective of this clinical trial is the progression free survival rate 12-months after start of treatment.

Conditions and MedDRA coding

recurrent platin sensitive low-grade serous ovarian-, fallopian tube- and/or primary peritoneal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Female, age at least 18 years.
2. Histologically diagnosed low-grade serous ovarian-, fallopian tube- and/or primary peritoneal cancer.
3. 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 (e.g. letrozole) is allowed. Neoadjuvant chemotherapy in the first line therapy will be counted as one line of therapy. Patients may, but are not required to, have a previous cytoreductive surgery in the first as well as in the second line.
4. Patients must have platinum sensitive disease, e.g. progression or recurrence after platinum-containing therapy, occurring no sooner than 6 months after completion of the last dose of platinum chemotherapy.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
6. Women of childbearing potential should not become pregnant while on the study therapy 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 study therapy. Women of childbearing potential must agree to follow contraceptive guidance in Appendix 3 of the protocol during the treatment period and for 6 months after receiving the last dose of the study therapy.
7. The participant provides written informed consent for the trial.
8. 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.
9. Have adequate organ and bone marrow function as defined in Table 1 of the study protocol.

Exclusion criteria 27

1. High-grade ovarian cancer or other than low grade serous ovarian cancer ovarian malignancy.
2. Persistent ≥Grade 2 non-hematologic toxicity from prior cancer therapy
3. 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).
4. 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.
5. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (time between last antineoplastic therapy and start of study therapy should be at least 4 weeks).
6. 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.
7. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
8. 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.
9. 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.
10. 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.
11. 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.
12. Has a bleeding tumor
13. 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.
14. Has hypersensitivity to platin-containing compounds other than carboplatin.
15. 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
16. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
17. Has an active infection requiring systemic therapy.
18. Has active infection with SARS-CoV-2 (antigen test).
19. Has a history of Human Immunodeficiency Virus (HIV) infection (known HIV1/HIV2 antibodies positive, mandatory testing for HIV during screening is required).
20. Has a history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or active Hepatitis C virus (defined as HCV RNA [qualitative] has been detected) infection (mandatory testing for Hepatitis B and Hepatitis C during screening is required).
21. Has a known history of active TB (Bacillus Tuberculosis).
22. 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.
23. Has had an allogenic tissue/ solid organ transplant.
24. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
25. 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
26. 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 according to § 40 Abs. 1 S. 3 Nr. 4 AMG).
27. Subjects that are depending on the sponsor/CRO or investigational site as well as on the investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 12-month (48 weeks) progression free survival (PFS) rate

Secondary endpoints 8

1. ORR, OS and PFS rate after 6, 12, 18 and 24 months
2. PFS and OS as time-to-event variables
3. Response rate (SD, PR or CR) after 6, 12, 18 and 24 months
4. Ki-67 expression <3.6% versus ≥3.6% and response rate and PFS
5. Safety Endpoints – safety of combination therapy (ctx and pembrolizumab) CTCAE v5.0 will be used as endpoint
6. Time of subsequent medical intervention
7. TFST and response (CR, PR, SD, PD) to first subsequent treatment
8. QoL (EORTC-QLQ-C30, EORTC-QLQ-OV-28) until 6 months after progress

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Nord-Ostdeutsche Gesellschaft Fuer Gynaekologische Onkologie e.V.

Sponsor organisation

Nord-Ostdeutsche Gesellschaft Fuer Gynaekologische Onkologie e.V.

Address

Schwedenstrasse 9, Wedding Wedding

City

Berlin

Postcode

13359

Country

Germany

Scientific contact point

Organisation

Nord-Ostdeutsche Gesellschaft Fuer Gynaekologische Onkologie e.V.

Contact name

Dr. Maren Keller

Public contact point

Organisation

Nord-Ostdeutsche Gesellschaft Fuer Gynaekologische Onkologie e.V.

Contact name

Dr. Maren Keller

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications