Phase 3 Real-world Effectiveness Of G-CSF In Pts with BC
Overview:
This is a phase 3 multi-center randomized controlled experiment. In Phase 3, 222 individuals are expected to be enrolled.
The chemotherapy in this study will consist of docetaxel, doxorubicin, and cyclophosphamide (TAC). These are some of the most active and widely used chemotherapeutic medicines for treating patients with breast cancer. TAC chemotherapy, in particular, has been used as an adjuvant treatment for HER2 negative early breast cancer patients with node positive illness, as well as node negative breast cancer patients with a high risk of recurrence.
Plinabulin is a new small chemical being researched to treat chemotherapy-induced neutropenia. Plurabulin will be given in a single dosage per cycle by IV infusion on the same day as (about 1 hour after) chemotherapy (TAC). Plinabulin is being researched to see if it may be used instead of G-CSF, pegfilgrastim, to avoid chemotherapy-induced neutropenia.
This experiment will be double-blind, with around 222 breast cancer patients expected to participate. Patients are allocated to one of the treatment arms at random, with 111 patients in each arm, with the arm designation and planned intervention as follows:
TAC + pegfilgrastim (6.0 mg) + placebo matching plinabulin in arm 1.
TAC + pegfilgrastim (6.0 mg) + plinabulin (Arm 2) (40 mg).
TAC (or TC for Cycles 2–4) will be delivered IV on Day 1 every 21 days for Cycles 1–4. Patients will be given a single dose of plinabulin or placebo IV over 30 minutes (5 minutes) in a double-blind fashion, 30 minutes after the end of the TAC (or TC for Cycles 2 to 4). All patients will receive a single dose of pegfilgrastim on Day 2 of each cycle (24 hours after completing chemotherapy) (6.0 mg).
Long-term safety follow-up will be undertaken on all subjects approximately every 6 months up to 5 years through patient interactions via phone calls, mail, or electronic methods; or medical record reviews.
DUBLIN-3 Phase III Study
Synopsis:
To compare the overall survival of NSCLC patients treated with docetaxel + plinabulin (DP Arm) for advanced or metastatic disease to patients treated with docetaxel + placebo (D5W) (D Arm).
The study's secondary goals are as follows:
To compare the overall response rate (ORR) of NSCLC patients receiving 2nd- or 3rd-line systemic therapy with docetaxel + plinabulin (DP Arm) to those receiving docetaxel + placebo (D5W) (D Arm).
To evaluate progression-free survival (PFS) of NSCLC patients receiving 2nd- or 3rd-line systemic therapy with docetaxel + plinabulin (DP Arm) to patients receiving docetaxel + placebo (D5W) (D Arm).
To evaluate the incidence of Grade 4 neutropenia (ANC 0.5 109/L) on Day 8 (+/- 1 day) of Cycle 1 in NSCLC patients receiving 2nd- or 3rd-line systemic treatment with docetaxel + plinabulin (DP Arm) to patients treated with docetaxel + placebo (D5W) (D Arm).
To compare the 24-month and 36-month OS rates of NSCLC patients treated with docetaxel + plinabulin (DP Arm) to those treated with docetaxel + placebo (D5W) (D Arm) for advanced or metastatic illness.
A Single-Arm, Phase II Study
Origins:
The presence of circulating tumor DNA (ctDNA) in patients (pts) after surgery indicates the presence of minimal/molecular residual disease (MRD) and a near-certain likelihood of disease recurrence. Because the likelihood of recurrence is considerable and therapeutic intervention may provide clinical benefit to patients, therapeutic techniques to treat MRD following standard curative therapy are required. Gevokizumab is a recombinant humanized monoclonal antibody that targets interleukin-1 (IL-1) in all stages of the cancer process (tumorigenesis, invasion, metastasis, angiogenesis, progression, and the modulation of anti-tumor immunity). Gevokizumab has been validated in pre-clinical colon cancer (CC) models, and its safety has been confirmed in late-stage clinical trials. We hope to assess the efficacy of gevokizumab in patients with early-stage CC with MRD (ctDNA positive) after final treatment in our ongoing trial.
Methodology:
NSABP FC-12 is a multi-center, single-arm phase II research that will enroll patients with stage II/III CC who test MRD+ within 6 weeks after completing curative surgery and 3 months of adjuvant chemotherapy. A tailored and tumor-informed ctDNA assay will be used to assess MRD (Signatera bespoke assay). Gevokizumab will be administered intravenously in a single dose of 120 mg every 28 days for 13 cycles. The primary outcome is one-year relapse-free survival (RFS) following the start of trial therapy. Secondary objectives include the rate of ctDNA clearance after 8 weeks of study therapy, as well as gevokizumab's safety, toxicity, pharmacokinetics, and immunogenicity. Endpoints associated with ctDNA clearance kinetics, tumor mutations, tumor mutational load, circulating methylated DNA, tumor immune microenvironment profile, peripheral blood immunological profile, and stool microbiome analyses will be explored and correlative. The enrollment duration is 12 months. Pts will be monitored for 18 months after enrollment, with ctDNA analysis at predetermined timepoints, until imaging shows recurrence of illness or death. CT scans will be performed every six months. RFS will be calculated in patients who clean ctDNA at 8 weeks against those who do not. A sample size of 31 (alpha=0.151; power 0.811) was used in a single-stage design to test the null hypothesis that the 12-mo RFS is P0.20 vs the alternative (HA) that P0.35. If 9 of 31 patients (29%) are alive and recurrence-free after 12 months, gevokizumab will be judged promising for further research. Enrollment progresses toward the primary goal. 05178576 is the clinical trial number.
