Clinical Trials Showcase

Programme stream(s): Treatment
Programme session type(s): Clinical Trials Showcase

16:30-17:45

Room: M1

This session presents the best trials submitted as abstracts for the Conference and reviewed by the Scientific Committee. Trials presented in the Clinical Trials Showcase are often practice-changing, of high quality and/or are presenting new data. This session is chaired by Professor Matt Seymour, NCRI and NIHR, UK.

Comparison of an oral factor Xa inhibitor with low molecular weight heparin in cancer patients with venous thromboembolism: results of the randomised select-d trial
Speaker: Annie Young
Affiliation:

Abstract:

Venous thromboembolism (VTE) is common in cancer patients. Long-term daily subcutaneous low molecular weight heparin has been the standard treatment for such patients. The aim of this study was to assess if an oral Factor Xa inhibitor, rivaroxaban, would offer an alternative treatment for VTE in the cancer population.

Method

In this UK multicentre, randomised, open-label, pilot trial, patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE or symptomatic lower extremity proximal deep vein thrombosis (DVT) were recruited. Allocation was to dalteparin (200 IU/kg daily, month 1, then 150 IU/kg, months 2-6) or rivaroxaban (15 mg twice daily for three weeks, then 20 mg once daily) for six months. DVT patients with residual DVT on compression ultrasound and patients with PE at presentation could be randomised to a further six months of rivaroxaban or placebo. The primary outcome was VTE recurrence over six months. Safety was assessed by major bleeding and clinically relevant non-major bleeding (CRNMB). A sample size of 400 patients would provide estimates of VTE recurrence to within +/‑ 4.5% assuming a rate of 10% at six months.

Results

Two hundred and three patients were randomised to each group; 58% of whom had metastases. Twenty-six patients experienced recurrent VTE (18 dalteparin, 8 rivaroxaban). The six month cumulative VTE recurrence rate with dalteparin was 11% (95% CI 7-16%) and 4% (95% CI 2-9%) with rivaroxaban (hazard ratio (HR) 0.43; 95% CI 0.19-0.99). The six month cumulative rate of major bleeding was 4% (95% CI 2-8%) for dalteparin and 6% (95% CI 3-11%) for rivaroxaban (HR 1.83; 95% CI 0.68-4.96). The corresponding rates of CRNMB were 4% (95% CI 2-9%) and 13% (95% CI 9-19%) respectively (HR 3.76; 95% CI 1.63-8.69).

Conclusion

Rivaroxaban was associated with relatively low VTE recurrence but higher CRNMB compared to dalteparin.

Tackling EArly Morbidity and Mortality in Myeloma (TEAMM): assessing the benefit of antibiotic prophylaxis and its effect on healthcare associated infections in 977 patients
Speaker: Janet Dunn
Affiliation: University of Warwick

Abstract:

TEAMM was a randomised, double-blind, placebo-controlled multi-centre phase III trial assessing benefits of antibiotic prophylaxis and effects on healthcare associated infections (HCAI). Infection is the biggest cause of early deaths in myeloma. Levofloxacin is effective against the common bacterial infections in myeloma but there is concern about the development of HCAI.

Method

Patients were randomised to receive 500 mg levofloxacin or placebo tablets once daily for 12 weeks, dose adjusted for renal function. Patients were eligible if >21 years old with newly diagnosed symptomatic myeloma, intention to treat myeloma actively, and were +/- 14 days into a programme of anti-myeloma treatment. Primary endpoint was the number of febrile episodes (temperature ≥38°C treated with anti-infectives) and/or death by any cause in the first 12 weeks obtained using Kaplan-Meier curves censored at 12 weeks. Febrile episodes, faecal and throat samples were collected at clinic visits every 4 weeks. Patients included in an intention to treat analyses. 

 

Results

TEAMM recruited 977 patients from August 2012-April 2016 from 92 centres within the UK. Median age 67 years, 63% male, 76% eGFR>50 ml/min, 54% planned high dose chemotherapy with autologous-stem cell transplantation, 93% ECOG performance status ≤2, 71% with bone disease. Primary endpoint showed a significant benefit for the use of levofloxacin with 95 of 489 patients (19%) on levofloxacin reporting events (87 febrile episodes; 4 deaths; 4 febrile episodes and death) versus 134 of 488 patients (27%) on placebo (112 febrile episodes; 15 deaths; 7 febrile episodes and death); hazard ratio 0.66 (95%CI 0.51-0.86) p=0.002. There was no increased carriage or infection with HCAI on Levofloxacin versus placebo.

Conclusion

Prophylactic use of 12 weeks levofloxacin for patients undergoing treatment for active myeloma significantly reduces febrile episodes and deaths without increasing HCAI.

Results of POUT - A phase III randomised trial of peri-operative chemotherapy versus surveillance in upper tract urothelial cancer (UTUC)
Speaker: Alison Birtle
Affiliation: Lancashire Teaching Hospitals NHS Foundation Trust

Abstract:

The role of chemotherapy post nephro-ureterectomy for UTUC is unclear. POUT (CRUK/11/027; NCT01993979) addresses whether adjuvant chemotherapy improves disease free survival (DFS) for patients with histologically confirmed pT2-T4 N0-3 M0 UTUC.


Method

Patients (up to 345), ≤90 days post NU, were randomised (1:1) to 4 cycles gemcitabine-cisplatin (gemcitabine-carboplatin if GFR 30-49ml/min) or surveillance.

Primary endpoint was DFS. The trial was powered to detect a hazard ratio (HR) of 0.65 (improvement in 3yr DFS from 40% to 55%; 2-sided alpha 5%, 80% power) with Peto-Haybittle early stopping rules.

Secondary endpoints included toxicity (CTCAE v4) and quality of life (QL; measured using QLQ-C30 and EQ-5D).

Results

261 participants (127 surveillance; 134 chemotherapy) were randomised between 31/05/2012-10/11/2017, at 57 centres. 252 participants joined the QL study. In Oct 2017, independent trial oversight committees recommended POUT recruitment closed as data collected met the early stopping rule for efficacy in favour of chemotherapy.

At time of interim analysis (5/09/2017), median follow-up was 17.6mths (IQR 7.5-33.6). Median age 69yrs, 30% pT2, 65% pT3; 91% pN0. Most common grade ≥3 toxicities for chemotherapy pts during treatment were neutropenia 29% (0% surveillance) & thrombocytopenia 7% (0%). 47/123 (surveillance) & 29/125 (chemotherapy) DFS events were reported; unadjusted HR=0.47 (95%CI: 0.29, 0.74) in favour of chemotherapy (log-rank p= 0.0009).

The difference in the mean change from baseline in QLQ-C30 global health status at 3 months was 7.7 (99% CI: 0.9, 14.6; p<0.001) in favour of surveillance and there was no difference between arms at 12 months (6.1 in favour of chemotherapy; 99% CI: -5.3, 17.4; p=0.08).

Conclusion

Adjuvant chemotherapy improved DFS in UTUC without adversely impacting QL. Recruitment to POUT was stopped early due to efficacy favouring chemotherapy; follow-up for OS continues. Results of POUT, the largest UTUC randomised trial, support adjuvant chemotherapy as a new standard of care.