Informations générales (source: ClinicalTrials.gov)
A Multicenter, Open-label, Randomized Phase II Study Aiming to Assess the Clinical Impact of Dostarlimab on Occurrence of Second Primary Cancer in Patients With Cured Primary Cancer (PREDOSTAR)
Interventional
Phase 2
Centre Leon Berard (Voir sur ClinicalTrials)
juillet 2023
mars 2029
16 juillet 2024
PredoSTAR is a multicenter, randomized, open-label phase II study proposed to patients at
high risk of SPC and in whom the treatment of the FPC does not include immunotherapy.
Dostarlimab treatment will be started within 6 months after the completion of treatment
for localized FPC (i.e. after the end of last CT, RT cure or surgery with a wash-out
period of 4 weeks before to start Dostarlimab). Eligible patients will be randomized
(1:1) to receive:
- Arm Dostarlimab : 4 intravenous (IV) injections of dostarlimab, Q3W or
- Arm No treatment
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Thomas PUDLARZ | 04/06/2024 12:00:47 | Contacter | ||
| 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 | Zoé NEVIERE | Contact (sur clinicalTrials) | |||
| Centre Jean Perrin - Clermont-Ferrand - France | Xavier DURANDO | Contact (sur clinicalTrials) | |||
| Centre Léon Bérard - 69008 - Lyon - France | Jean-Yves BLAY, MD,PhD | Contact (sur clinicalTrials) | |||
| Institut Claudius Regaud - Toulouse - France | Victor SARRADIN | Contact (sur clinicalTrials) | |||
| Institut Gustave Roussy - Villejuif - France | Thomas PUDLARZ | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Male or female patient ≥18 years of age at time of informed consent form signature.
Note - Patients with childhood first primary cancer (FPC) are eligible.
- Patients with prior histologically proven primary solid tumors (any type), AJCC
stage I, II or III or IV if M0, eligible to curative treatment. Note - Time between
end of treatment for first cancer and randomisation must be <6 months.
- Patients with at least one risk factor for second primary cancer (SPC) including:
- Exposure to exogenous risk factor : tobacco (>20YP) ≥ 10 years and still active at
time of FPC diagnosis and/or Endogenous risk factors (genetic predisposition
including for instance germ line mutations of p53 or BRCA genes, Lynch syndrome, or
any mutations of genes known to be associated with higher risk of cancer according
to current list from French National Cancer institute or HPV-related FPC.
- Availability of FFPE tumor sample from FPC initial diagnosis for histological
comparison in case/at time of SPC. Note - Histological report must be sent to the
sponsor with archival FFPE tumor block within 14 days after randomisation.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or .
- Adequate hematologic and end-organ function, defined by the following laboratory
test results:
- WBC ≥ 2.5 x 109/L,
- Hemoglobin ≥ 9.0 g/dL. Patients may be transfused (> 2 weeks before randomisation)
to meet this criterion,
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without granulocyte colony-stimulating
factor support within 2 weeks before randomisation,
- Platelets ≥ 100 x 109/L,
- Lymphocyte count ≥ 0.5 x 109/L;
- Serum creatinine clearance ≥30 mL/min/1.73m2 (MDRD or CKD-EPI formula - See
Appendix) or serum creatinine ≤1.5 ULN
- Serum bilirubin ≤ 1.5 × Upper Limit of Normal (ULN), with the following exception:
Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be
enrolled;
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline
phosphatase (ALP) ≤ 2.5 x ULN;
- Prothrombin time/INR ≤ 1.5, or, if patient is receiving therapeutic anticoagulation,
prothrombin time/INR < 3.0
- aPTT ≤ ULN OR, if patient is receiving therapeutic anticoagulation, aPTT must be <
1.5 ULN. Note: Patient receiving therapeutic anticoagulation must be on stable dose.
- Proteinuria by urine dipstick < 2+ or 24-hour proteinuria ≤ 1.0 g.
- Corrected QT interval (QTc) <450msec (or QTc <480msec for participants with bundle
branch block).
- Women patients of child-bearing potential are eligible, provided they have a
negative serum or urine pregnancy and agrees to use adequate contraception for up to
6 months after the final dose of dostarlimab.
- Fertile men must agree to use an effective method of contraception during the study
and for up to 6 months after the last dose of dostarlimab.
- Patient should understand, sign, and date the written voluntary informed consent
form prior to any protocol-specific procedures performed and should be able and
willing to comply with study visits and procedures as per protocol.
- Patients must be covered by a medical insurance in country where applicable.
- Male or female patient ≥18 years of age at time of informed consent form signature.
Note - Patients with childhood first primary cancer (FPC) are eligible.
- Patients with prior histologically proven primary solid tumors (any type), AJCC
stage I, II or III or IV if M0, eligible to curative treatment. Note - Time between
end of treatment for first cancer and randomisation must be <6 months.
- Patients with at least one risk factor for second primary cancer (SPC) including:
- Exposure to exogenous risk factor : tobacco (>20YP) ≥ 10 years and still active at
time of FPC diagnosis and/or Endogenous risk factors (genetic predisposition
including for instance germ line mutations of p53 or BRCA genes, Lynch syndrome, or
any mutations of genes known to be associated with higher risk of cancer according
to current list from French National Cancer institute or HPV-related FPC.
- Availability of FFPE tumor sample from FPC initial diagnosis for histological
comparison in case/at time of SPC. Note - Histological report must be sent to the
sponsor with archival FFPE tumor block within 14 days after randomisation.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or .
- Adequate hematologic and end-organ function, defined by the following laboratory
test results:
- WBC ≥ 2.5 x 109/L,
- Hemoglobin ≥ 9.0 g/dL. Patients may be transfused (> 2 weeks before randomisation)
to meet this criterion,
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without granulocyte colony-stimulating
factor support within 2 weeks before randomisation,
- Platelets ≥ 100 x 109/L,
- Lymphocyte count ≥ 0.5 x 109/L;
- Serum creatinine clearance ≥30 mL/min/1.73m2 (MDRD or CKD-EPI formula - See
Appendix) or serum creatinine ≤1.5 ULN
- Serum bilirubin ≤ 1.5 × Upper Limit of Normal (ULN), with the following exception:
Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be
enrolled;
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline
phosphatase (ALP) ≤ 2.5 x ULN;
- Prothrombin time/INR ≤ 1.5, or, if patient is receiving therapeutic anticoagulation,
prothrombin time/INR < 3.0
- aPTT ≤ ULN OR, if patient is receiving therapeutic anticoagulation, aPTT must be <
1.5 ULN. Note: Patient receiving therapeutic anticoagulation must be on stable dose.
- Proteinuria by urine dipstick < 2+ or 24-hour proteinuria ≤ 1.0 g.
- Corrected QT interval (QTc) <450msec (or QTc <480msec for participants with bundle
branch block).
- Women patients of child-bearing potential are eligible, provided they have a
negative serum or urine pregnancy and agrees to use adequate contraception for up to
6 months after the final dose of dostarlimab.
- Fertile men must agree to use an effective method of contraception during the study
and for up to 6 months after the last dose of dostarlimab.
- Patient should understand, sign, and date the written voluntary informed consent
form prior to any protocol-specific procedures performed and should be able and
willing to comply with study visits and procedures as per protocol.
- Patients must be covered by a medical insurance in country where applicable.
- Previous treatment with immunotherapy (any types) for cured first primary cancer.
- Acute and ongoing toxicities from previous therapy that have not resolved to Grade ≤
1, except for alopecia, neuropathy and lab values presented in inclusion criteria.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28
days prior to randomisation, or abdominal surgery, abdominal interventions or
significant abdominal traumatic injury within 60 days prior to randomisation or
anticipation of need for major surgical procedure during the course of the study or
non-recovery from side effects of any such procedure.
- Treatment with systemic immunosuppressive medication (including, but not limited to,
corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-TNF-alpha agents) within 2 weeks prior to randomisation, or anticipation of
need for systemic immunosuppressive medication during study treatment; with the
exceptions of intranasal, inhaled, or topical corticosteroids or systemic
corticosteroids at physiological doses, which are not to exceed 10 mg/day of
prednisone, or an equivalent corticosteroid.
- Systemic immunostimulatory agents (including, but not limited to, interferons and
IL-2) are prohibited within 4 weeks or five half-lives of the drug (whichever is
longer) prior to randomisation.
- Oral or IV antibiotics within 14 days of randomisation.
- History of severe allergic or other hypersensitivity reactions to:
- chimeric or humanized antibodies or fusion proteins,
- biopharmaceuticals produced in Chinese hamster ovary cells, or
- any component of the dostarlimab formulation
- Concurrent treatment with any approved or investigational anti-cancer treatment or
participation in another clinical trial with therapeutic intent. Note -
Hormonotherapy as part of standard of care is allowed.
- History of autoimmune disease including (see Appendix 18.5 for a more comprehensive
list of pre-existing autoimmune diseases and immune deficiencies and exceptions in
the protocol.
- Infectious diseases:
- active infection requiring IV antibiotics,
- severe infection within 4 weeks prior to randomisation, including, but not
limited to, hospitalization for complications of infection, bacteremia, or
severe pneumonia,
- active hepatitis B (chronic or acute; defined as having a positive hepatitis B
surface antigen [HBsAg] test at screening),
- active hepatitis C. Patients positive for hepatitis C virus (HCV) antibody are
eligible only if PCR is negative for HCV RNA at screening,
- HIV infection,
- active tuberculosis,
- influenza vaccination should be given during influenza season. Patients must
not receive live attenuated influenza vaccine (e.g., FluMist®) within 4 weeks
prior to randomisation or at any time during the study.
- Significant cardiovascular disease: see details in the protocol.
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic
organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan.
- Evidence of significant uncontrolled concomitant disease that could affect
compliance with the protocol or interpretation of results, including significant
liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior
vena cava syndrome).
- Patient with FPC known to be at high risk of relapse defined as ≥ 70% relapse from
FPC within 2 years.
- Patient patients who are solid organ recipients.
- Patient with primary cancer of unknown origin (CUP).
- Pregnant or lactating women