Combination Immunotherapy in Rare Cancers Under InvesTigation

Sponsor
Olivia Newton-John Cancer Research Institute
Study ID
NCT04969887
Phase
PHASE2
Status
Active Not Recruiting

Conditions

  • Advanced Biliary Tract Cancer
  • Female Reproductive System Neoplasm
  • MSI-H Solid Malignant Tumor
  • Neuroendocrine Tumors

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Ipilimumab — DRUG
    CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) is a key regulator of T cell activity. Ipilimumab is a CTLA-4 immune checkpoint inhibitor that blocks T-cell inhibitory signals induced by the CTLA-4 pathway, increasing the number of tumor reactive T effector cells which mobilize to mount a direct T-cell immune attack against tumor cells. CTLA-4 blockade can also reduce T regulatory cell function, which may lead to an increase in anti-tumor immune response.
  • Nivolumab — DRUG
    A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death-1 (PD-1,PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs (antigen presenting cells). This results in the activation of T-cells and cell-mediated immune responses against tumor cells or pathogens. Activated PD-1 negatively regulates T-cell activation and and plays a key role in in tumor evasion from host immunity.

Study Details

The four tumour streams that will be studied in this protocol are based on immunotherapy sensitive rare cancers from CA209-538 which will be further investigated under this protocol and divided into four groups: 1. Neuroendocrine cancers: Atypical bronchial carcinoid, neuroendocrine carcinoma and Grade 3 NETs independent of primary site (SCLC excluded) 2. Biliary tract cancers: Intrahepatic cholangiocarcinoma and gallbladder carcinoma 3. Gynaecological malignancies: Ovarian clear cell carcinoma, uterine clear cell carcinoma, uterine/ovarian carcinosarcoma, uterine leiomyosarcoma and vaginal/vulva squamous cell carcinoma 4. Mismatch repair protein deficient (MSI-H) cancers (excluding colorectal carcinoma). The role of immunotherapy is being defined in more common cancer types, however because of their rarity, the efficacy of immunotherapy for these cancers is poorly defined. This protocol provides an important opportunity to establish whether the combination of nivolumab \& ipilimumab has efficacy in these cancers.

Key Dates

Start date
Aug 3, 2021
Status verified
Feb 2026
Primary completion
Mar 1, 2025
Completion
Mar 1, 2027

Study Design

Enrollment
240 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Ipilimumab and Nivolumab
    All Subjects will be treated with: Nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg concurrently every 3 weeks for 4 doses followed by nivolumab only at 480mg every 4 weeks until progression (up to 2 years)

Primary Outcome Measure

Confirm the clinical efficacy of ipi/nivo in rare cancer histotypes which have demonstrated to be responsive to the regimen in the CA209-538 study. [ Time Frame: At 12 weeks following registration then as assessed by standard care until progression. ]

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