NCIC CLINICAL TRIALS GROUP DATA SAFETY MONITORING COMMITTEE Friday, 1 May 2009 SUMMARY REPORT

Size: px

Start display at page:

Download "NCIC CLINICAL TRIALS GROUP DATA SAFETY MONITORING COMMITTEE Friday, 1 May 2009 SUMMARY REPORT"

Beatrice Richards
6 years ago
Views:

1 NCIC CLINICAL TRIALS GROUP DATA SAFETY MONITORING COMMITTEE Friday, 1 May 2009 SUMMARY REPORT The NCIC CTG DSMC reviewed the following trials with respect to safety, trial conduct, including accrual, and where applicable, efficacy. In addition to trial-related data, where applicable, relevant data from external sources (e.g., recently published literature) were also considered. Open NCI US-Affiliated Trials MA.17R A double blind re-randomization to letrozole or placebo for women completing five years of adjuvant letrozole in the MA.17 study Activation Date: October 14, 2004 Recommendation: No concerns; review in the Fall. PR.11 A Phase III Study of Active Surveillance Therapy Against Radical Treatment in Patients Diagnosed with Favourable Risk Prostate Cancer (START) Activation Date: June 15, 2007 Recommendation: Accrual continues to be a concern. Accrual is expected to get beyond the 20% of projected accrual threshold by the DSMC s next meeting. Closed NCI US-affiliated Trials BR.19 A phase III prospective randomized double blind placebo controlled trial of the epidermal growth factor receptor antagonist ZD1839 (IRESSA) in completely resected Stage 1B, II, and IIIA nonsmall cell lung cancer Closing Date: April 22, 2005 DSMC Summary Report, 1 May 2009 Page 1

2 HD.6 A phase III study of radiotherapy or ABVD plus radiotherapy versus BVD alone in the treatment of early stage Hodgkin's disease Closing Date: April 05, 2002 MA.20 A phase III study of regional radiation therapy in early breast cancer Closing Date: February 2, 2007 MA.21 A phase III adjuvant trial of sequenced EC + filgrastim + epoetin alfa followed by paclitaxel versus sequenced AC followed by paclitaxel versus CEF as therapy for premenopausal women and early postmenopausal women who have had potentially curative surgery for node positive or high risk node negative breast cancer Closing Date: April 29, 2005 MA.27 A randomized phase III trial of exemestane versus anastrozole in postmenopausal women with receptor positive primary breast cancer Closing Date: July 31, 2008 Recommendation: Continue the trial as. DSMC wonders why the futility analysis was conducted this late in the trial. Final analysis is expected in mid-summer Review in the Fall. Additional Requests: 1. A request to conduct a masked analysis by arm on early pilot data collected on the MA.27D breast density study from Dr. Celine Vachon at the NCCTG. APPROVED. 2. A request for permission to submit a patient specific expanded database to a proposed collaborative meta-analysis of individual participant data from randomized trials involving selective cyclo-oxygenase-2 inhibitors or nonsteroidal anti-inflammatory drugs. APPROVED. 3. use the second interim analysis data from MA.27 with both treatment arms combined together to examine in aromatase inhibitor treated patients, whether the appearance of new vasomotor or joint symptoms within the first 3 months of starting therapy is associated with breast cancer relapse free survival. APPROVED. DSMC Summary Report, 1 May 2009 Page 2

3 Director s Response: Recommendations accepted. The Group s Director will provide a detailed rationale to the DSMC regarding the justification for amending the protocol to include an assessment of futility with the second protocol-defined interim analysis. PR.3 Intergroup (NCIC CTG, CUOG, SWOG, MRC-UK) phase III randomized trial comparing total androgen blockade versus total androgen blockade plus pelvic irradiation in clinical adenocarcinoma of the prostate Closing Date: August 31, 2005 Recommendation: Review in the Fall. Interim analysis report should be made available as soon as possible. PR.7 A phase III randomized trial comparing intermittent versus continuous androgen suppression for patients with Prostate-Specific-Antigen progression in the clinical absence of distant metastases following radiotherapy for prostate cancer Closed to accrual: November 30, 2005 Recommendation: No issues. Review in the Spring. Additional Request: A request for the early release of trial data from the PR.7 trial as a correlative substudy of the trial: Effect of Intermittent versus Continuous Androgen Suppression on Bone Loss and Body Composition in a Phase III Randomized Trial -- APPROVED. Director s Response: Recommendations accepted Open Non-NCI US-Affiliated Trials B1.1 Phase III Trial Of Combined Gemcitabine Plus Capecitabine Chemotherapy Versus Gemcitabine Alone In Advanced Biliary Cancer Activation Date: March 19, 2008 Recommendation: Accrual is slow. Review in the Fall.. Since the DSMC s meeting and in view of new data that became available at the 2009 Meeting of the American Society of Clinical Oncology, the Trial Committee is reviewing the continued conduct of this trial. DSMC Summary Report, 1 May 2009 Page 3

4 BR.29 A double blind randomized trial of cediranib (AZD2171) versus placebo in patients receiving paclitaxel/carboplatin chemotherapy for the treatment of advanced or metastatic non-small cell lung cancer Activation Date: November 6, 2008 CE.6 A Randomized Phase III Study of Temozolomide and Short-Course Radiation vs. Short-Course Radiation Alone in the Treatment of Newly Diagnosed Glioblastoma Multiforme in Elderly Patients Activation Date: May 1, 2007 Recommendation: Accrual is slow, but trial should be allowed to continue for one further year to allow groups a chance to contribute. Review in the Fall. CO.20 A Phase III Randomized Study of Brivanib Alaninate (BMS ) in Combination with Cetuximab (Erbitux) Versus Placebo in Combination with Cetuximab (Erbitux) in Patients Previously Treated With Combination Chemotherapy for Metastatic Colorectal Carcinoma Activation Date: February 5, 2008 Recommendation: Request trial team comment on toxicity profiles. No accrual concerns. Review in the Fall.. The Trial Committee will provide a comment on the toxicity profiles presented to the DSMC. CO.21 A phase III study of the impact of a physical activity program on disease-free survival in patients with high risk stage II or stage III colon cancer: A randomized controlled trial (Challenge) Activation Date: December 3, 2008 Recommendation: No issues. Review in the Fall. HN.6 A phase III study of standard fractionation radiotherapy with concurrent high-dose cisplatin versus accelerated fractionation radiotherapy with panitumumab in patients with locally-advanced stage III and IV squamous cell carcinoma of the head and neck Activation Date: December 18, 2008 Recommendation: No issues. Review in the Fall. DSMC Summary Report, 1 May 2009 Page 4

5 LY.12 A phase III study of gemcitabine, dexamethasone, and cisplatin compared to dexamethasone, cytarabine, and cisplatin plus/minus rituximab as salvage chemotherapy for patients with relapsed or refractory aggressive histology non-hodgkin's lymphoma prior to autologous stem cell transplant and followed by maintenance rituximab versus observation Activation Date: August 7, 2003 Recommendation: Request from trial team another analysis (response rates) with updated data and include transplantation rate as well. Trial biostatistician should discuss analysis plans with DSMC primary reviewers.. The DSMC has requested an additional interim analysis of the primary outcome. The Trial Committee will develop a Statistical Analysis Plan (SAP) to account for this request. Before performing this analysis, other stakeholders, including the DSMC, will be provided with the opportunity to comment on the SAP. MA.22 A phase I/II study of increasing doses of epirubicin and docetaxel plus pegfilgrastim for locally advanced or inflammatory breast cancer Activation Date: February 25, 2003 MA.29 A Feasibility Study of Pre-Operative Sunitinib (SU11248) With Multiple Pharmacodynamic Endpoints in Patients with T1c-T3 Operable Carcinoma of the Breast Activation Date: 12 March 2007 Recommendation: Monitor accrual. Review in the Fall. MA.31 A Randomized, Open-Label, Phase III Study of Taxane Based Chemotherapy with Lapatinib or Trastuzumab as First-Line Therapy for Women with HER2/neu Positive Metastatic Breast Cancer Activation Date: 17 July 2008 Recommendation: Monitor accrual. Review in the Fall. DSMC Summary Report, 1 May 2009 Page 5

6 MAP.3 A phase III randomized study of exemestane versus placebo in postmenopausal women at increased risk of developing breast cancer Activation Date: February 11, 2004 Recommendation: Inquire about missing Gail scores as it is a stratification factor; off treatment should be included in the trial report; ask trial team to comment on toxicities and whether they are in line with what is to be expected. Review in the Fall.. The Trial Committee will provide the DSMC with the requested information. PR.12 Phase III Study of Neoadjuvant Docetaxel And Androgen Suppression Plus Radiation Therapy Versus Androgen Suppression Alone Plus Radiation Therapy For High-Risk Localized Adenocarcinoma Of The Prostate (DART) Activation Date: March 3, 2008 Recommendation: Monitor accrual. Review in the Fall. SC.20 A phase III international randomized trial of single versus multiple fractions for re-irradiation of painful bone metastases Activation Date: January 7, 2004 Recommendation: The first interim analysis was received and reviewed. Trial should continue. Sample size should be increased to 850 as suggested in the current interim analysis to adjust for the non-evaluable rate.. The process of expanding the sample size will require review and comment from the Trial Committee, other participating cooperative groups and by the NCIC CTG s Clinical Trials Committee. Closed Non-NCI US-Affiliated Trials BL.11 A phase III study of Iressa in combination with intravesical BCG versus intravesical BCG alone in high risk superficial transitional cell carcinoma of the bladder Activation Date: April 12, 2006 Closed: December 4, 2008 (Failure to meet target accrual; as recommended by DSMC, 19 November 2008) DSMC Summary Report, 1 May 2009 Page 6

7 BR.25 A phase II study of hypofractionated 3-dimensional conformal radiotherapy (3DCRT) for inoperable stage I/II non-small cell lung cancer (NSCLC) Activation Date: April 26, 2006 Closed: 18 April 2008 Accrual met LY.13 A multi-centre phase II trial investigating the efficacy and tolerability of bortezomib added to cyclophosphamide, vincristine, prednisone and rituximab (BCVP-R) for patients with advanced stage follicular non-hodgkin's lymphoma requiring systemic first-line treatment Activation Date: December 14, 2006 Closed: March 6, 2009 (accrual met) MY.10 A randomized phase III study of thalidomide and prednisone as maintenance therapy following autologous stem cell transplant in patients with multiple myeloma Activation Date: September 16, 2002 Closed: January 30, 2009 The 3 rd interim analysis was received. There is now a full publication of the results of the Australian study, which is similar in design to MY.10 (Consolidation Therapy With Low- Dose Thalidomide and Prednisolone Prolongs the Survival of Multiple Myeloma Patients Undergoing a Single Autologous Stem-Cell Transplantation Procedure. Spencer A, et. al. J Clin Oncol 2009; 27: ). In this trial, progression-free survival is improved, as was seen with other published reports. While most patients will likely be past the point of considering maintenance therapy, the DSMC agreed that all active patients still on study should be informed of these results. This requires a re-consent process. Recommendation: All trial investigators and patients on the study should be informed of these results (April 2009 data) improvement in PFS to determine whether they want to continue their assigned management strategy in an expedited fashion. Patients are to be reconsented. DSMC Summary Report, 1 May 2009 Page 7

NCIC CLINICAL TRIALS GROUP DATA SAFETY MONITORING COMMITTEE Fall Conference Call 23 November 2009 SUMMARY REPORT

NCIC CLINICAL TRIALS GROUP DATA SAFETY MONITORING COMMITTEE Fall Conference Call 23 November 2009 SUMMARY REPORT The NCIC CTG DSMC reviewed the following trials with respect to safety, trial conduct, including