NCT03598270: ANITA

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

Completed Phase 3 Last updated 30 August 2024

What this trial tests

Phase 3 trial testing Placebo in Recurrent Ovarian Carcinoma in 417 participants. Completed in 5 August 2024.

Timeline

21 November 2018

Primary endpoint
5 August 2024

5 August 2024

Quick facts

Lead sponsor	Grupo Español de Investigación en Cáncer de Ovario
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	417
Start date	21 November 2018
Primary completion	5 August 2024
Estimated completion	5 August 2024
Sites	71 locations across France, Italy, Belgium, Germany, Spain

Drugs / interventions tested

• Placebo
• Carboplatin
• Paclitaxel — full drug profile →
• Niraparib (niraparib) — full drug profile →
• Gemcitabine
• Pegylated liposomal doxorubicin (PLD) (pegylated-liposomal-doxorubicin-pld) — full drug profile →
• Atezolizumab

Conditions studied

• Recurrent Ovarian Carcinoma — all drugs for Recurrent Ovarian Carcinoma →

Sponsor

Grupo Español de Investigación en Cáncer de Ovario — full company profile →

Who can join

18 and older, female only, with Recurrent Ovarian Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
   Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
2. Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology.
   Vanmeerbeek I, Sprooten J, De Ruysscher D, Tejpar S, et al · · 2020 · cited 179× · PMID 32002302 · DOI 10.1080/2162402x.2019.1703449
3. Tumor Microenvironment in Ovarian Cancer: Function and Therapeutic Strategy.
   Yang Y, Yang Y, Yang J, Zhao X, et al · · 2020 · cited 168× · PMID 32850861 · DOI 10.3389/fcell.2020.00758
4. Combined PARP Inhibition and Immune Checkpoint Therapy in Solid Tumors.
   Peyraud F, Italiano A. · · 2020 · cited 163× · PMID 32526888 · DOI 10.3390/cancers12061502
5. Therapeutic Potential of Combining PARP Inhibitor and Immunotherapy in Solid Tumors.
   Vikas P, Borcherding N, Chennamadhavuni A, Garje R. · · 2020 · cited 130× · PMID 32457830 · DOI 10.3389/fonc.2020.00570
6. Prospects for combining immune checkpoint blockade with PARP inhibition.
   Li A, Yi M, Qin S, Chu Q, et al · · 2019 · cited 100× · PMID 31521196 · DOI 10.1186/s13045-019-0784-8
7. Targeting DNA repair pathway in cancer: Mechanisms and clinical application.
   Wang M, Chen S, Ao D. · · 2021 · cited 84× · PMID 34977872 · DOI 10.1002/mco2.103
8. Current status and future prospects of PARP inhibitor clinical trials in ovarian cancer.
   Jiang X, Li W, Li X, Bai H, et al · · 2019 · cited 75× · PMID 31191001 · DOI 10.2147/cmar.s200524