Imperial College London

MrPhilipBadman

Faculty of MedicineDepartment of Surgery & Cancer

Clinical Trials Operations Manager
 
 
 
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Contact

 

+44 (0)20 7594 2796p.badman

 
 
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Location

 

CR UK Convergence Science CentreRoderic Hill BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

10 results found

Allsopp RC, Guo Q, Page K, Bhagani S, Kasim A, Badman P, Kenny L, Stebbing J, Shaw JAet al., 2024, Circulating tumour DNA dynamics during alternating chemotherapy and hormonal therapy in metastatic breast cancer: the ALERT study., Breast Cancer Res Treat

PURPOSE: Although changes in circulating tumour DNA (ctDNA) in breast cancer are well described, the kinetics of their fluctuations has not been described over short timescales. We investigated ctDNA dynamics during alternating cycles of chemotherapy and hormonal treatment in pre-treated patients with oestrogen receptor-positive metastatic breast cancer. METHODS: Patients received alternating, 9-week cycles of eribulin and aromatase inhibitors (AIs). The clinical primary endpoint, progression-free survival (PFS), was monitored at 3, 6 and 9 months; secondary endpoints, clinical benefit rate (CBR), safety and tolerability profiles, were also assessed. Importantly, ctDNA fluctuations were monitored using the Oncomine™ Breast cfDNA assay to test whether biomarkers may change rapidly between chemotherapy and aromatase inhibitor (AI) treatment in the setting of advanced breast cancer, potentially reflecting disease dynamics. RESULTS: The median PFS was 202 days (95% CI: 135-undefined) and 235 days (95% CI: 235-undefined) at 6 and 9 months, respectively, with a 50% CBR at both 6 and 9 months. Dynamic changes in ctDNA were observed in short timescales between chemotherapy and AI treatment and support the clinical benefit (CB) seen in individual patients and, critically, appear informative of acquired resistance in real time. CONCLUSION: Changes in ctDNA can occur rapidly and reflect changes in patients' clinical tumour responses (NCT02681523).

Journal article

Lythgoe M, Dama P, Frampton AE, Pickford E, Tookman L, Cunnea P, Fotopoulou C, Liu D, Clark J, Lozano-Kuehne J, Badman PD, Clarke A, Chetal S, Fyvie G, Stevenson A, Krell Jet al., 2023, Immune modulation and the oral live biotherapeutic product, MRx0518, in treatment-naive patients with cancer: Updated safety data, Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X

Conference paper

Seckl M, Ghorani E, Quartagno M, Blackhall FH, Gilbert DC, O'Brien MER, Ottensmeier CHH, Pizzo E, Spicer JF, Williams A, Badman PD, Parmar MKBet al., 2023, REFINE-Lung: A multicentre phase III study to determine the optimal frequency of pembrolizumab in non-small cell lung cancer utilising a novel multi-arm design, Publisher: American Society of Clinical Oncology, Pages: TPS9145-TPS9145, ISSN: 0732-183X

Conference paper

Ghorani E, Quartagno M, Blackhall F, Gilbert DC, O'Brien M, Ottensmeier C, Pizzo E, Spicer J, Williams A, Badman P, Parmar MKB, Seckl MJet al., 2023, REFINE-Lung implements a novel multi-arm randomisedtrial design to address possible immunotherapy overtreatment, The Lancet Oncology, Vol: 24, Pages: E219-E227, ISSN: 1213-9432

Increasing evidence suggests that some immunotherapy dosing regimens for patients with advanced cancer could result in overtreatment. Given the high costs of these agents, and important implications for quality of life and toxicity, new approaches are needed to identify and reduce unnecessary treatment. Conventional two-arm non-inferiority designs are inefficient in this context because they require large numbers of patients to explore a single alternative to the standard of care. Here, we discuss the potential problem of overtreatment with anti-PD-1 directed agents in general and introduce REFINE-Lung (NCT05085028), a UK multicentre phase 3 study of reduced frequency pembrolizumab in advanced non-small-cell lung cancer. REFINE-Lung uses a novel multi-arm multi-stage response over continuous interventions (MAMS-ROCI) design to determine the optimal dose frequency of pembrolizumab. Along with a similarly designed basket study of patients with renal cancer and melanoma, REFINE-Lung and the MAMS-ROCI design could contribute to practice-changing advances in patient care and form a template for future immunotherapy optimisation studies across cancer types and indications. This new trial design is applicable to many new or existing agents for which optimisation of dose, frequency, or duration of therapy is desirable.

Journal article

Coombes RC, Badman PD, Lozano-Kuehne JP, Liu X, Macpherson IR, Zubairi I, Baird RD, Rosenfeld N, Garcia-Corbacho J, Cresti N, Plummer R, Armstrong A, Allerton R, Landers D, Nicholas H, McLellan L, Lim A, Mouliere F, Pardo OE, Ferguson V, Seckl MJet al., 2023, Author Correction: Results of the phase IIa RADICAL trial of the FGFR inhibitor AZD4547 in endocrine resistant breast cancer., Nature Communications, Vol: 14, Pages: 1-1, ISSN: 2041-1723

Journal article

Coombes R, Badman P, Lozano-Kuehne JP, Liu X, Macpherson IR, Baird RD, Rosenfeld N, Garcia-Corbacho J, Cresti N, Plummer R, Armstrong A, Allerton R, Landers D, Nicholas H, McLellan L, Lim A, Mouliere F, Pardo OP, Seckl MJet al., 2022, Results of the Phase IIa RADICAL trial of the FGFR inhibitor AZD4547 in endocrine resistant breast cancer, Nature Communications, Vol: 13, ISSN: 2041-1723

We conducted a phase IIa, multi-centre, open label, single arm study (RADICAL; NCT01791985) of AZD4547 (a potent and selective inhibitor of Fibroblast Growth Factor Receptor (FGFR)-1, 2 and 3 receptor tyrosine kinases) administered with anastrozole or letrozole in estrogen receptor positive metastatic breast cancer patients who had become resistant to aromatase inhibitors. After a safety run-in study to assess safety and tolerability, we recruited 52 patients. The primary endpoint was change in tumour size at 12 weeks, and secondary endpoints were to assess response at 6 weeks, 20 weeks and every 8 weeks thereafter and tolerability of the combined treatment. Two partial responses (PR) and 19 stable disease (SD) patients were observed at the 12-week time point. At 28 weeks, according to centrally reviewed Response Evaluation Criteria in Solid Tumours (RECIST) criteria, five PR and 8 SD patients were observed in 50 assessable cases. Overall, objective response rate (5 PR) was of 10%, meeting the pre-specified endpoint. Fourteen patients discontinued due to adverse events. Eleven patients had retinal pigment epithelial detachments which was asymptomatic and reversible in all but one patient. Exploratory ribonucleic acid sequencing (RNA-Seq) analysis was done on patients’ samples: 6 differentially-expressed-genes could distinguish those who benefited from the addition of AZD4547.

Journal article

Rosenthal AN, Fraser LSM, Philpott S, Manchanda R, Burnell M, Badman P, Hadwin R, Rizzuto I, Benjamin E, Singh N, Evans DG, Eccles DM, Ryan A, Liston R, Dawnay A, Ford J, Gunu R, MacKay J, Skates SJ, Menon U, Jacobs IJet al., 2017, Evidence of Stage Shift in Women Diagnosed with Ovarian Cancer during Phase II of the United Kingdom Familial Ovarian Cancer Screening Study, Obstetrical and Gynecological Survey, Vol: 72, Pages: 338-340, ISSN: 0029-7828

Journal article

Seckl M, Badman PD, Liu X, MacPherson LR, Zubairi IH, Baird RD, Garcia-Corbacho J, Crest N, Plummer ER, Armstrong AC, Allerton R, Landers D, Nicholas H, McLellan L, Lim AK, Coombes Cet al., 2017, RADICAL trial: A phase lb/IIa study to assess the safety and efficacy of AZD4547 in combination with either anastrozole or letrozole in ER positive breast cancer patients progressing on these aromatase inhibitors (AIs)., 53rd Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X

Conference paper

Rosenthal AN, Fraser LSM, Philpott S, Manchanda R, Burnell M, Badman P, Hadwin R, Rizzuto I, Benjamin E, Singh N, Evans DG, Eccles DM, Ryan A, Liston R, Dawnay A, Ford J, Gunu R, Mackay J, Skates SJ, Menon U, Jacobs IJ, United Kingdom Familial Ovarian Cancer Screening Study collaboratorset al., 2017, Evidence of Stage Shift in Women Diagnosed With Ovarian Cancer During Phase II of the United Kingdom Familial Ovarian Cancer Screening Study., J Clin Oncol, Vol: 35, Pages: 1411-1420

Purpose To establish the performance of screening with serum cancer antigen 125 (CA-125), interpreted using the risk of ovarian cancer algorithm (ROCA), and transvaginal sonography (TVS) for women at high risk of ovarian cancer (OC) or fallopian tube cancer (FTC). Patients and Methods Women whose estimated lifetime risk of OC/FTC was ≥ 10% were recruited at 42 centers in the United Kingdom and underwent ROCA screening every 4 months. TVS occurred annually if ROCA results were normal or within 2 months of an abnormal ROCA result. Risk-reducing salpingo-oophorectomy (RRSO) was encouraged throughout the study. Participants were observed via cancer registries, questionnaires, and notification by centers. Performance was calculated after censoring 365 days after prior screen, with modeling of occult cancers detected at RRSO. Results Between June 14, 2007, and May 15, 2012, 4,348 women underwent 13,728 women-years of screening. The median follow-up time was 4.8 years. Nineteen patients were diagnosed with invasive OC/FTC within 1 year of prior screening (13 diagnoses were screen-detected and six were occult at RRSO). No symptomatic interval cancers occurred. Ten (52.6%) of the total 19 diagnoses were stage I to II OC/FTC (CI, 28.9% to 75.6%). Of the 13 screen-detected cancers, five (38.5%) were stage I to II (CI, 13.9% to 68.4%). Of the six occult cancers, five (83.3%) were stage I to II (CI, 35.9% to 99.6%). Modeled sensitivity, positive predictive value, and negative predictive value for OC/FTC detection within 1 year were 94.7% (CI, 74.0% to 99.9%), 10.8% (6.5% to 16.5%), and 100% (CI, 100% to 100%), respectively. Seven (36.8%) of the 19 cancers diagnosed < 1 year after prior screen were stage IIIb to IV (CI, 16.3% to 61.6%) compared with 17 (94.4%) of 18 cancers diagnosed > 1 year after screening ended (CI, 72.7% to 99.9%; P < .001). Eighteen (94.8%) of 19 cancers diagnosed < 1 year after prior screen had zero residual disease (with lower surgical compl

Journal article

Rosenthal AN, Fraser L, Manchanda R, Badman P, Philpott S, Mozersky J, Hadwin R, Cafferty FH, Benjamin E, Singh N, Evans DG, Eccles DM, Skates SJ, Mackay J, Menon U, Jacobs IJet al., 2013, Results of annual screening in phase I of the United Kingdom familial ovarian cancer screening study highlight the need for strict adherence to screening schedule., J Clin Oncol, Vol: 31, Pages: 49-57

PURPOSE: To establish the performance characteristics of annual transvaginal ultrasound and serum CA125 screening for women at high risk of ovarian/fallopian tube cancer (OC/FTC) and to investigate the impact of delayed screening interval and surgical intervention. PATIENTS AND METHODS: Between May 6, 2002, and January 5, 2008, 3,563 women at an estimated ≥ 10% lifetime risk of OC/FTC were recruited and screened by 37 centers in the United Kingdom. Participants were observed prospectively by centers, questionnaire, and national cancer registries. RESULTS: Sensitivity for detection of incident OC/FTC at 1 year after last annual screen was 81.3% (95% CI, 54.3% to 96.0%) if occult cancers were classified as false negatives and 87.5% (95% CI, 61.7% to 98.5%) if they were classified as true positives. Positive and negative predictive values of incident screening were 25.5% (95% CI, 14.3 to 40.0) and 99.9% (95% CI, 99.8 to 100) respectively. Four (30.8%) of 13 incident screen-detected OC/FTCs were stage I or II. Compared with women screened in the year before diagnosis, those not screened in the year before diagnosis were more likely to have ≥ stage IIIc disease (85.7% v 26.1%; P = .009). Screening interval was delayed by a median of 88 days before detection of incident OC/FTC. Median interval from detection screen to surgical intervention was 79 days in prevalent and incident OC/FTC. CONCLUSION: These results in the high-risk population highlight the need for strict adherence to screening schedule. Screening more frequently than annually with prompt surgical intervention seems to offer a better chance of early-stage detection.

Journal article

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