Informations générales (source: ClinicalTrials.gov)
A Randomized, Multicenter, Open Label, Phase I/II Study to Evaluate the Safety, Clinical and Biological Activity of a Humanized Monoclonal Antibody Targeting Netrin-1 (NP137) in Combination with Carboplatin Plus Paclitaxel And/or Pembrolizumab in Patients with Locally Advanced/metastatic Endometrial Carcinoma or Cervix Carcinoma Progressing/relapsing After At Least One Prior Systemic Chemotherapy. (GYNET)
Interventional
Phase 1/Phase 2
NETRIS Pharma (Voir sur ClinicalTrials)
décembre 2020
juillet 2026
09 octobre 2024
The aim of this study is to investigate the safety and the clinical activities of NP137
when combined with pembrolizumab and/or chemotherapies in patients with
advanced/metastatic gynecological cancers (2 types: endometrial carcinoma and cervix
carcinoma).
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/06/2024 14:01:21 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Alexandra LEARY | 12/04/2024 07:44:33 | Contacter | ||
| CLCC RENE HUGUENIN INSTITUT CURIE | 04/12/2024 12:44:03 | Contact (sur clinicalTrials) | |||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Eugène Marquis - Rennes - France | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre François Baclesse - Caen - France | Contact (sur clinicalTrials) | ||||
| Centre Georges François Leclerc - Dijon - France | Contact (sur clinicalTrials) | ||||
| Centre Léon Bérard - Lyon - France | Contact (sur clinicalTrials) | ||||
| CHRU BESANCON - Hopital Jean Minjoz - Besançon - France | Contact (sur clinicalTrials) | ||||
| Hopital de la Croix Saint Simon - 75020 - Paris - France | Contact (sur clinicalTrials) | ||||
| ICM - Val d'Aurelle - Montpellier - France | Contact (sur clinicalTrials) | ||||
| Insitut de cancérologie de l'ouest - Nantes - France | Contact (sur clinicalTrials) | ||||
| Institut Bergonié - Bordeaux - France | Contact (sur clinicalTrials) | ||||
| Institut claudius Regaud - Toulouse - France | Contact (sur clinicalTrials) | ||||
| Institut Curie (Site Saint Cloud) - 92210 - Paris - France | Contact (sur clinicalTrials) | ||||
| Primary Completion Date - Lille - France | Contact (sur clinicalTrials) | ||||
| Primary Completion Date - Marseille - France | Contact (sur clinicalTrials) | ||||
Critères
Femme
Inclusion Criteria:
- Be women ≥ 18 years at time of inform consent signature.
- Patient with histologically confirmed locally advanced / metastatic endometrial
carcinoma (Endometrial sarcoma are excluded) or patient with histologically
confirmed locally advanced / metastatic cervix adeno- or epidermoid- carcinoma.
- Previously treated by at least one line of platinum based chemotherapy, but no more
than 3 lines of chemotherapies whatever the nature. If the previous based platinum
chemotherapy was given as neoadjuvant or adjuvant chemotherapy for a local disease
(stage I or II), inclusion must be performed no more than one year after the end of
this chemotherapy, except if an advanced or metastatic relapse has been documented
and treated by a systemic anti-cancer agent during this time interval.
In all cases, a minimal wash-out period of 6 months after completion of last chemotherapy
with [platinum + paclitaxel] is required prior to entering the study.
Platinum chemotherapy concomitant to RT can not be considered as a line of previous
platinum based chemotherapy.
- For endometrium carcinoma: mutational profile (MSI/MSS status) available before
randomization (see St Paul de Vence 2019- ARCAGY - GINECO Group recommendation).
- 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.
- 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 together with an associated pathology report.
Note: If submitting unstained cut slides, newly cut slides should be submitted to the
testing laboratory within 14 days from the date slides are cut (details pertaining to
tumor tissue submission can be found in the laboratory manual).
- Optional for patients having consented to tumor 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 are not adequate lesions for biopsies and lymph nodes lesions should not be
considered as prime targets.
- Life expectancy ≥ 3 months.
- Eastern Cooperative Oncology GrougGroup performance status (ECOG PS) of 0 to 1.
- Demonstrate adequate cardiovascular function:
- QTcF < 470ms
- Resting BP systolic <160mmHg and diastolic < 100mmHg
- LVEF > 50% as determined by transthoracic echocardiogram.
- Demonstrate adequate organ function as defined in protocol, all screening laboratory
tests should be performed within 7 days prior C1D1:
- Women of child-bearing potential must have a negative urine pregnancy test at
screening (within 72 hours prior 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 6 months after the end of their treatment.
- Patient should understand, sign, and date the written voluntary informed consent
form prior to any protocol-specific procedures.
- Patient should be able and willing to comply with study visits and procedures as per
protocol.
- Be women ≥ 18 years at time of inform consent signature.
- Patient with histologically confirmed locally advanced / metastatic endometrial
carcinoma (Endometrial sarcoma are excluded) or patient with histologically
confirmed locally advanced / metastatic cervix adeno- or epidermoid- carcinoma.
- Previously treated by at least one line of platinum based chemotherapy, but no more
than 3 lines of chemotherapies whatever the nature. If the previous based platinum
chemotherapy was given as neoadjuvant or adjuvant chemotherapy for a local disease
(stage I or II), inclusion must be performed no more than one year after the end of
this chemotherapy, except if an advanced or metastatic relapse has been documented
and treated by a systemic anti-cancer agent during this time interval.
In all cases, a minimal wash-out period of 6 months after completion of last chemotherapy
with [platinum + paclitaxel] is required prior to entering the study.
Platinum chemotherapy concomitant to RT can not be considered as a line of previous
platinum based chemotherapy.
- For endometrium carcinoma: mutational profile (MSI/MSS status) available before
randomization (see St Paul de Vence 2019- ARCAGY - GINECO Group recommendation).
- 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.
- 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 together with an associated pathology report.
Note: If submitting unstained cut slides, newly cut slides should be submitted to the
testing laboratory within 14 days from the date slides are cut (details pertaining to
tumor tissue submission can be found in the laboratory manual).
- Optional for patients having consented to tumor 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 are not adequate lesions for biopsies and lymph nodes lesions should not be
considered as prime targets.
- Life expectancy ≥ 3 months.
- Eastern Cooperative Oncology GrougGroup performance status (ECOG PS) of 0 to 1.
- Demonstrate adequate cardiovascular function:
- QTcF < 470ms
- Resting BP systolic <160mmHg and diastolic < 100mmHg
- LVEF > 50% as determined by transthoracic echocardiogram.
- Demonstrate adequate organ function as defined in protocol, all screening laboratory
tests should be performed within 7 days prior C1D1:
- Women of child-bearing potential must have a negative urine pregnancy test at
screening (within 72 hours prior 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 6 months after the end of their treatment.
- Patient should understand, sign, and date the written voluntary informed consent
form prior to any protocol-specific procedures.
- Patient should be able and willing to comply with study visits and procedures as per
protocol.
- Patients with progression during previous chemotherapy with [platinum +paclitaxel]
- Persistence of CTCAE ≥ Grade 2 toxicity due to prior anti-cancer therapy (except
alopecia (any grades).
- History of severe (≥Grade 3) allergic anaphylactic reactions to one of the
components of NP137, pembrolizumab, paclitaxel, carboplatin and/or any of their
excipients.
- 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 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.
- 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 :
- Chemotherapy or targeted therapies (approved or investigational) within 2 weeks or
5* t1/2 whichever is longer prior C1D1.
- Hormonal therapy within 1 week prior to C1D1
- Biological therapy within 4 weeks prior to C1D1
- Are currently participating in or have participated in a study of an
investigational agent or have 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.
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 or live-attenuated vaccine within 30 days prior to the
first dose of study drug. Note: killed vaccinesare 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.
- 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, Sjögren's syndrome, Guillain-Barre syndrome,
multiple sclerosis, vasculitis, or glomerulonephritis with the following exceptions:
- Patients with a history of autoimmune-related hypothyroidism who are on stable
thyroid replacement hormone therapy,
- Patients with controlled Type 1 diabetes mellitus,
- patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis would
be excluded) are eligible provided that they meet the following conditions:
- Rash must cover less than 10% of body surface area (BSA).
- Disease is well controlled at baseline and only requiring low potency
topical steroids.
- No acute exacerbations of underlying condition within the previous 12
months requiring PUVA [psoralen plus ultraviolet A radiation],
methotrexate, retinoid, biologic agents, oral calcineurin inhibitors, high
potency or oral steroids.
- Patients with HIV, active B or C hepatitis infection. Notes: Active hepatitis B i.e.
chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg]
test at screening before C1D1. Patients with past hepatitis B virus (HBV) infection
or resolved HBV infection (defined as the presence of hepatitis B core antibody
[anti-HBc] and absence of HBsAg) are eligible. HBV DNA test must be performed in
these patients prior to C1D1. Patients with a positive HBcAb test must have a
negative HBV DNA test at screening. Active hepatitis C i.e. Patients positive for
hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA at
screening.
- Patients with active tuberculosis.
- Prior allogeneic bone marrow transplantation or solid organ transplant for another
malignancy in the past.
- History of idiopathic pulmonary fibrosis, non-infectious pneumonitis / interstitial
lung disease that required steroids or has current pneumonitis / interstitial lung
disease , drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis
obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on
screening chest CT scan.
- Have an active infection requiring systemic therapy.