12 research outputs found
The ACT-ONE trial, a multicentre, randomised, double-blind, placebo-controlled, dose-finding study of the anabolic/catabolic transforming agent, MT-102 in subjects with cachexia related to stage III and IV non-small cell lung cancer and colorectal cancer: study design
Aims Cachexia, the wasting disorder associated with a wide
range of serious illnesses including cancer, is a major cause of morbidity and mortality. There is currently no widely approved therapeutic agent for treating or preventing
cancer-associated cachexia. Colorectal cancer and nonsmall
cell lung cancer have relatively high incidences of cachexia, approximately 28% and 34%, respectively.
Neurohormonal overactivity has been implicated in the
genesis and progression of cachexia and beta receptor
antagonism has been proposed as a potential therapy.
MT-102, a novel anabolic/catabolic transforming agent,
has a multi-functional effect upon three potential pharmacological targets in cancer cachexia, namely reduced
catabolism through non-selective β-blockade, reduced
fatigue, and thermogenesis through central 5-HT1a
antagonism and increased anabolism through partial β-2
receptor agonism.
Methods At least 132 male and female patients, aged
between 25 and 80 years with a confirmed diagnosis of
late-stage non-small cell lung cancer or colorectal cancer,
with cachexia will be randomised to either one of the two
MT-102 doses or placebo in a 3:1:2 ratio (MT-102
10 mg BD−1/MT-102 2.5 mg BD/placebo). Patients will
continue on study treatment for maximally 16 weeks. The
primary endpoint, to be analysed by assigned treatment
group, will be body weight change over 16 weeks. For this
endpoint, the study has 85% power (0.05% significance
level) to detect per 4-week period a mean change of −0.8 kg
in the placebo group and 0 kg in the high-dose MT-102
arm. The first patient was randomised in February 2011 and
patient recruitment is expected to continue until mid-2012.
Perspective The ACT-ONE trial is designed to test whether
the anabolic/catabolic transforming agent MT-102 will
positively impact on the rate of change of body weight in
cancer cachexia, thereby evaluating a novel therapeutic
strategy in this hitherto poorly treatable condition. A
separate ACT-TWO trial will recruit patients who complete
the ACT-ONE trial and remain on randomised double-blind
medication. Participants in ACT-TWO will be followed for
an additional period with a separate primary endpoint
Evaluation of quality of life from a phase II study of anamorelin HCl in NSCLC patients.
Efficacy and safety of adding the retinoid tamibarotene or placebo to paclitaxel/carboplatin for advanced non-small cell lung cancer.
ADXS11-001 immunotherapy targeting HPV-E7: Final results from a phase 2 study in Indian women with recurrent cervical cancer.
A Real-World Study of Safety, Immunogenicity and Efficacy of Bevacizumab in Patients With Solid Malignancies: A Phase IV, Post-Marketing Study in India
Objective: The aim of this study was to evaluate the post-marketing safety, tolerability, immunogenicity and efficacy of Bevacizumab (manufactured by Hetero Biopharma) in a broader population of patients with solid tumors. Patients And Methods: This phase IV, prospective, multi-centric clinical study was carried out in Indian patients with solid malignancies (metastatic colorectal cancer, non-squamous non-small-cell lung cancer, metastatic renal cell carcinoma) treated with Bevacizumab between April 2018 and July 2019. This study included 203 patients from 16 tertiary care oncology centers across India for safety assessment, of which a subset of 115 patients who have consented were also evaluated for efficacy and immunogenicity. This study was prospectively registered in the Clinical Trial Registry of India (CTRI), and was commenced only after receiving approval from the competent authority (Central Drugs Standard Control Organization, CDSCO). Results: Out of the 203 enrolled patients, 121 (59.6%) patients reported 338 adverse events (AEs) during this study. Of 338 reported AEs, 14 serious adverse events (SAEs) were reported by 13 patients including 6 fatal SAEs, assessed as unrelated to the study medication and 7 non-fatal SAEs, 5 assessed as related, and 3 unrelated to Bevacizumab. Most AEs reported in this study (33.9%) were general disorders and administration site conditions, followed by gastrointestinal disorders (29.1%). The most frequently reported AEs were diarrhea (11.3%), asthenia (10.3%), headache (8.9%), pain (7.4%), vomiting (7.9%), and neutropenia (5.9%). At the end of the study, 2 (1.75%) of 69 patients reported antibodies to Bevacizumab without affecting safety and efficacy. However, at the end of 12 months, no patient had reported antibodies to Bevacizumab. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were reported in 18.3%, 22.6%, 9.6%, and 8.7% of patients, respectively. The overall response rate (CR + PR) was reported in 40.9% of patients at the end of the study. Disease control rate (DCR), also known as the clinical benefit rate (CBR) was reported in 50.4% of patients. Conclusions: Bevacizumab (Cizumab, Hetero Biopharma) was observed to be safe, well tolerated, lacking immunogenicity, and efficacious in the treatment of solid tumors. The findings of this phase IV study of Bevacizumab, primarily as a combination therapy regimen suggest its suitability and rationality for usage in multiple solid malignancies. Clinical Trial Registry Number: CTRI/2018/4/13371 [Registered on CTRI http://ctri.nic.in/Clinicaltrials/advsearch.php : 19/04/2018]; Trial Registered Prospectively