Why was this trial needed?
Brain metastases occur in occur in more than 25% of brain cancer patients [1]. The prognosis for these patients remains poor and can be associated with severe cognitive, sensorial, and neurological impairments. Recent advances in breast cancer therapies have made major improvements in survival, but patients with brain metastases are often excluded from these clinical trials, making the utility of these drugs unknown for this patient population. Additionally, there is an increasing number of patients with central nervous system (CNS) involvement due in part to these improvements in systemic treatments and palliative support, as well as early detection.
The standard treatments for breast cancer with brain metastases are radiosurgery and radiation therapy [2], but there is no defined strategy once these local treatments fail to slow the progression, creating a large unmet need.
What is the PHENOMENAL study evaluating?
MEDSIR’s PHENOMENAL study is evaluating a treatment for patients with HER2 negative metastatic breast cancer with CNS involvement. Specifically, the study is assessing the safety and efficacy of nanoliposomal irinotecan (nal-IRI). Nal-IRI is a nanoparticle formation of irinotecan (a topoisomerase 1 inhibitor) encapsulated in a liposome drug delivery system. This formulation has been designed to overcome the pharmacological and clinical limitations of the conventional (non-liposomal) formulation of the drug, to maximize the antitumor activity and to minimize the toxicity.
Nal-IRI has been previously studied in patients with cervical cancer, gastric cancer, pancreatic cancer, and colorectal cancer. It is currently being studied for glioma, breast cancer, and several pediatric solid tumors. In patients with metastatic pancreatic cancer, nal-IRI combined with fluorouracil and folinic acid demonstrated improvements in overall survival and overall response rate, ultimately leading to approval by FDA for the use after progressing on gemcitabine [3].
Trial Design
The PHENOMENAL study (NCT03328884) is an open-label, phase II clinical trial to evaluate the efficacy and safety of nal-IRI for progressing brain metastases in patients with HER2 negative breast cancer.
The primary objective of the study is to assess efficacy, as defined as intracranial objective response rate as determined by the Response Assessment in Neuro-Oncology Brain Metastases criteria with central confirmation by a volumetric parameter. The trial will also assess the efficacy of treatment defined by objective response rate, clinical benefit ratio at 12 weeks, disease control rate, progression-free survival, time to response, duration of response, maximum tumor shrinkage, and overall survival in patients with progressing brain metastases and in all patients with CNS involvement. Safety and tolerability of nal-IRI in all patients will also be a secondary objective. As an exploratory objective the study will assess efficacy of nal-IRI in patients with stable brain metastases.
The trial is currently recruiting patients in 16 sites across Spain. Contact us to learn more about this trial!
References:
1. M. Simsek, A. Aliyev, T. Baydas, M. Besiroglu, T. Demir, A. T.m. Shbair, M. Seker, H.M. Turk. 2022. “Breast Cancer Patients with Brain Metastases: A Cross-Sectional Study.” The Breast Journal. 2022:5763810. doi: 10.1155/2022/5763810.
2. Gil-Gil, M. J., M. Martinez-Garcia, A. Sierra, G. Conesa, S. Del Barco, S. González-Jimenez, and S. Villà. 2014. “Breast Cancer Brain Metastases: A Review of the Literature and a Current Multidisciplinary Management Guideline.” Clinical & Translational Oncology: Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 16 (5): 436–46. doi:10.1007/s12094-013-1110-5.
3. Wang-Gillam, A., L. Chung-Pin, G. Bodoky, A. Dean, Y.S. Shan, G. Jameson, T. Macarulla, et al. 2016. “Nanoliposomal Irinotecan with Fluorouracil and Folinic Acid in Metastatic Pancreatic Cancer after Previous Gemcitabine-Based Therapy (NAPOLI-1): A Global, Randomised, Open-Label, Phase 3 Trial.” Lancet (London, England) 387 (10018): 545–57. doi:10.1016/S0140-6736(15)00986-1.
