Platinum-based Chemotherapy With Atezolizumab and Niraparib in Patients With Recurrent Ovarian Cancer

Sponsor
Grupo Español de Investigación en Cáncer de Ovario
Study ID
NCT03598270
Phase
PHASE3
Status
Completed

Conditions

  • Recurrent Ovarian Carcinoma

Eligibility Criteria

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

Interventions

  • Placebo — DRUG
    Volume equivalent to 1200 mg of atezolizumab drug product. Intravenous Day 1
  • Carboplatin — DRUG
    Intravenous. Day 1
  • Paclitaxel — DRUG
    175 mg/m². Intravenous. Day 1
  • Niraparib — DRUG
    200 mg or 300 mg. Oral. From day 1 to 21
  • Gemcitabine — DRUG
    1000 mg/m². Intravenous. Day 1 and day 8.
  • Pegylated liposomal doxorubicin (PLD) — DRUG
    30 mg/m². Intravenous. Day 1
  • Atezolizumab — DRUG
    1200 mg. Intravenous. Day 1

Study Details

Atezolizumab in this study is expected to have a positive benefit-risk profile for the treatment of patients with platinum-sensitive relapse of ovarian cancer. Of interest, atezolizumab is being investigated also in combination with platinum-based doublet chemotherapy in second line (2L)/ third line (3L) platinum-sensitive recurrent ovarian cancer patients in ATALANTE (NCT02891824), which also includes bevacizumab in the combination. The study is proceeding as expected after \>100 patients enrolled and under independent Data Monitoring Committee (IDMC) supervision. Platinum-containing therapy is considered the treatment of choice for patients with platinum-sensitive relapse. However the duration of response and the prolongation of the progression free interval with chemotherapy are usually brief, among other because these chemotherapy regimens cannot be continued until progression as they are associated with neurological, renal and hematological toxicity and cannot generally be tolerated for more than about 6 to 9 cycles. Niraparib received FDA approval in March 2017 as maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. Recently, the European Medicines Agency (EMA) has also approved niraparib as maintenance monotherapy. Despite the progress brought about by niraparib, there is a need for a more effective treatment to extend the progression free interval in this patient population. The combination with immune checkpoint inhibitors such as anti-death protein 1 (anti-PD1) or anti-death protein ligand 1 (anti-PD-L1) has a compelling rationale to this aim, especially under the light of the emerging clinical data of this combination. The use of atezolizumab concurrent to platinum-containing chemotherapy followed by niraparib as maintenance therapy after completion of chemotherapy, as per normal clinical practice, may provide further benefit to patients in terms of prolonging the progression free interval and increasing the interval between lines of chemotherapy, hence delaying further hospitalization and the cumulative toxicities associated with chemotherapy. Additionally, preliminary studies with atezolizumab suggest an acceptable tolerability profile for long term clinical use in recurrent ovarian cancer patients and other indications.

Key Dates

Start date
Nov 21, 2018
Status verified
Aug 2024
Primary completion
Aug 5, 2024
Completion
Aug 5, 2024

Study Design

Enrollment
417 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Placebo Comparator: Arm A (Control Arm)
    Placebo of atezolizumab in combination with one of the platinum based regimens below (investigator's choice) followed by maintenance niraparib with placebo: * Carboplatin (AUC = 5, d1) plus paclitaxel and placebo every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks * Carboplatin (AUC = 4, d1) plus gemcitabine and placebo every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks. * Carboplatin (AUC = 5, d1) plus pegylated liposomal doxorubicin (PLD) and placebo every 4 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with placebo every 3 weeks.
  • Experimental: Arm B (experimental arm)
    Atezolizumab in combination with one of the platinum based regimens below (investigator's choice) followed by maintenance niraparib with atezolizumab: * Carboplatin (AUC = 5, d1) plus paclitaxel and atezolizumab every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. * Carboplatin (AUC = 4, d1) plus gemcitabine and atezolizumab every 3 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks. * Carboplatin (AUC = 5, d1) plus pegylated liposomal doxorubicin (PLD) and atezolizumab every 4 weeks. Non-progressing patients will be switched to maintenance niraparib in combination with atezolizumab every 3 weeks.

Primary Outcome Measure

Progression-free survival (PFS) [ Time Frame: 30 months ]

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