GYNecological cancers treated with NETrin Abs in combination with chemotherapy and/or Pembrolizumab
- Conditions
- ocally advanced/metastatic endometrial carcinoma or cervix carcinoma progressing/relapsing after at least one prior systemic chemotherapy.MedDRA version: 21.1Level: PTClassification code 10014734Term: Endometrial cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10014733Term: Endometrial cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10001197Term: Adenocarcinoma of the cervixSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10008342Term: Cervix carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10014987Term: Epidermoid carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000172-38-FR
- Lead Sponsor
- ETRIS PHARMA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 240
I1. Be women = 18 years at time of inform consent signature.
I2. Patient with histologically confirmed locally advanced / metastatic endometrial carcinoma or cervix adenocarcinoma or epidermoid carcinoma.
I3. Previously treated by at least one line of chemotherapy, but no more than 3 lines. A minimal wash-out period of 6 months after completion of last chemotherapy with platinum and paclitaxel is required prior to entering the study.
I4. For endometrium carcinoma: Mutational profile (MSI/MSS status) available before randomization (see St Paul de Vence 2019- ARCAGY – GINECO Group recommendation)
I5. Documented disease progression as per RECIST V1.1 after prior systemic chemotherapy regimen and presence of at least one lesion evaluable for response according to RECIST 1.1
I6. Have provided a representative archival tumor sample in formalin-fixed paraffin embedded (FFPE) block (primary tumor or metastasis) or newly obtained core or excisional biopsy of a tumor lesion toghether with an associated pathology report.
I7.Optional for patient having consented to tumour biopsies : Presence of at least one tumor lesion visible by medical imaging and accessible to repeatable percutaneous sampling that permits core needle biopsy without unacceptable risk of a significant procedural complications, and suitable for retrieval of 4 cores using a 16-gauge diameter needle or larger.
Note: lesions to be biopsied should not be selected as RECIST target lesions. Bone lesions arare not adequate for biopsies and lymph nodes lesions should not be considered as prime targets for biopsies.
I8.Life expectancy = 3 months.
I9.Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1.
I10. Demonstrate adequate organ function as defined in table page 45 (section 2.3.1 inclusion criteria. all screening laboratory tests should be performed within 7 days prior C1D1)
I11. Women of child-bearing potential must have a negative serum pregnancy test at screening (Pregnancy testing (urine) should be within 72 hours of C1D1) and must agree to use 2 effective forms of contraception from the time of the treatment period and of the negative pregnancy test up 120 days after the last dose of IMP (NP137 and/or Pembrolizumab) or 6 months after the last CT study drugs for patient in Arm A (CT only) or if patient discontinue NP137 and/or Pembrolizumab before the end of their CT.
I12. Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures.
I13. Patient should be able and willing to comply with study visits and procedures as per protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120
E1. Persistence of CTCAE = Grade 2 toxicity due to prior anti-cancer therapy (except alopecia (any grades), Grade =1 peripheral neuropathy).
E2. History of (=Grade 3) allergic anaphylactic reactions to one of the components of NP137, pembrolizumab, paclitaxel, carboplatin and/or any of their excipients.
E3. 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.
E4. Has a known additional malignancy that is progressing or has required active treatment within the past 2 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.
E5. Prior/concomitant Therapy:
- Have 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) and was discontinued from that treatment due to a Grade =3 irAE
- Have received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment, C1D1.
- Have received prior radiotherapy within 4 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.
- Have had major surgery within 4 weeks of start of study treatment. Participants must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment, C1D1.
- Have 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.
- Have received immunosuppressive medication within 2 weeks with the exceptions of intranasal, topical and inhaled corticosteroids or systemic corticosteroids at doses which are not to exceed 10 mg/day of prednisone, or equivalent doses of another corticosteroid
E6. Have a history of autoimmune disease that has required systemic treatment in 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) is not considered a form of systemic treatment and is allowed.
- History of autoimmune disease which include but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method