PREventing Second Cancers With DOSTARlimab

NCT05855811 | Recruiting Phase 2 DMC

• 1 other identifier: ET22-215
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Recurrent Cancer; Primary Cancer; Second Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of Second Primary Cancer (SPC) in patients who have completed curative treatment for a First Primary Cancer (FPC).

  Second primary invasive cancer must be centrally histologically confirmed

  Up to 3 years

Secondary Outcomes (6)

• Rate of SPC

  Up to 3 years

• Time to SPC

  Up to 3 years

• Event Free survival

  Up to 3 years

• Overall Survival since randomisation and since SPC

  Up to 3 years

• Recurrence of FPC.

  Up to 3 years

Other Outcomes (2)

• Molecular profiles of SPC and immune infiltrate characterisation by WES analysis (tumor samples)

  From FPC material and in case of SPC (biopsy diagnostic or surgery)

• Immune parameters definition by cytometry analysis (blood samples)

  At inclusion, 30 days after the last injection and in case of SPC (at diagnostic timing)

Study Arms (2)

Dostarlimab

EXPERIMENTAL

4 intravenous injections maximum of dostarlimab, 500mg, every 3 weeks

Drug: Dostarlimab

No treatment

NO INTERVENTION

Interventions

Dostarlimab DRUG

Dostarlimab should initiated within 6 months after the end of treatment for FPC.

Dostarlimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• Previous treatment with immunotherapy (any types) for cured first primary cancer.
• 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),

Sponsors & Collaborators

• Centre Leon Berard: lead
• GlaxoSmithKline: collaborator

Study Sites (5)

Centre François Baclesse

Caen, France

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, France

RECRUITING

Centre Léon Bérard

Lyon, 69008, France

RECRUITING

Institut Claudius Regaud

Toulouse, France

RECRUITING

Institut Gustave Roussy

Villejuif, France

RECRUITING

MeSH Terms

Conditions

Recurrence; Neoplasms; Neoplasms, Second Primary

Interventions

dostarlimab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Jean-Yves BLAY, MD, PhD

CONTACT

4 78 78 51 26; jean-yves.blay@lyon.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Analysis will be performed according the ITT principe and will include all randomized patients. Incidence of events by arm will be compared assuming a Poisson distribution. Cumulative incidence curves against time will we compared between treatment arms. Follow-up of each patient will be calculated from randomisation to death or last follow-up for alive patients.

Study Record Dates

• First Submitted: May 4, 2023
• First Posted: May 11, 2023
• Study Start: July 26, 2023
• Primary Completion (Estimated): July 26, 2028
• Study Completion (Estimated): March 26, 2029
• Last Updated: July 15, 2024

Record last verified: 2024-07

Locations

FR (5)