|There were four recent publications -- three reporting primary results (Canadian Cancer Trials Group BR.29, Canadian Cancer Trials Group IND.190, and Canadian Cancer Trials Group CXC.1 [GOG 0219]) and the other related Canadian Cancer Trials Group MA.14.
Canadian Cancer Trials Group BR.29 - A Double Blind Randomized Trial of Cediranib versus Placebo in Patients Receiving Paclitaxel/Carboplatin Chemotherapy for the Treatment of Advanced or Metastatic Non-Small Cell Lung Cancer
This randomized double-blind placebo-controlled study evaluated the addition of cediranib, an inhibitor of vascular endothelial growth factor receptors 1-3, to standard carboplatin/paclitaxel chemotherapy in advanced non-small cell lung cancer. The trial was halted for futility at the interim analysis and a final analysis was performed on all 306 enrolled patients. The authors report that the addition of cediranib increased response rate, but did not significantly improve progression-free survival. Additionally, cediranib patients had more grade 3 hypertension, diarrhea and anorexia.
Laurie SA, Solomon BJ, Seymour L, Ellis PM, Goss GD, Shepherd FA, Boyer MJ, Arnold AM, Clingan P, Laberge F, Fenton D, Hirsh V, Zukin M, Stockler MR, Lee CW, Chen EX, Montenegro A, Ding K, Bradbury PA. Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: Canadian Cancer Trials Group study BR29. Eur J Can 50: 706-12, 2014.
Canadian Cancer Trials Group IND.190 - A Phase I-II Trial of MK-0646, a Monoclonal Antibody Against Insulin-Like Growth Factor-1 Receptor in Combination with Etoposide and Cisplatin in Extensive Stage Small Cell Lung Cancer
The insulin-like growth factor receptor is a potential target in small-cell lung cancer. The study investigators conducted a phase I study of cisplatin, etoposide plus dalotuzumab. Two dose levels of dalotuzumab were evaluated in combination with cisplatin and etoposide for patients with chemotherapy-naive extensive-stage small-cell lung cancer. Primary outcome was determination of the recommended phase 2 dose. Secondary outcomes included response rate and toxicity. The investigators conclude that dalotuzumab can be combined at full dose with standard doses of cisplatin and etoposide. The observed toxicities were consistent with that expected from cisplatin and etoposide except for hyperglycemia, which seems to be dose dependent.
Ellis PM, Shepherd FA, Laurie SA, Goss GD, Olivo M, Powers J, Seymour L, Bradbury PA. Canadian Cancer Trials Group IND.190 Phase I Trial of Dalotuzumab (MK-0646) in Combination with Cisplatin and Etoposide in Extensive-Stage Small-Cell Lung Cancer. J Thoracic Oncol 9: 410-3, 2014.
Canadian Cancer Trials Group CXC.1 (GOG 0219) - A Phase III, Randomized Trial of Weekly Cisplatin and Radiation versus Cisplatin and Tirapazamine and Radiation in Stage 1B2, IIA, IIB, IIIB and IVA Cervical Carcinoma Limited to the Pelvis
The purpose of the trial was designed to test the effectiveness and safety of adding the hypoxic cell sensitizer tirapazamine (TPZ) to standard cisplatin (CIS) chemoradiotherapy in locally advanced cervix cancer. Progression-free survival was evaluable in 387 of 402 patients randomly assigned over 36 months, with enrollment ending in September 2009. Because of the lack of TPZ supply, the study did not reach its original target accrual goal. Investigators concluded that TPS/CIS chemoradiotherapy was not superior to CIS chemoradiotherapy in either PFS or OS, although definitive commentary was limited by an inadequate number of events (progression or death). TPZ/CIS chemoradiotherapy was tolerable at a modified starting dose.
DiSilvestro PA, Ali S, Craighead PS, Lucci JA, Lee YC, Cohn DE, Spirtos NM, Tewari l of Weekly Cisplatin and Irradiation Versus Cisplatin and Tirapazamine and Irradiation in Stages IB2, IIA, IIB, IIIB, and IVA Cervical Carcinoma Limited to the Pelvis: A Gynecologic Oncology Group Study. J Clin Oncol 32: 458-64, 2014.
Canadian Cancer Trials Group MA.14 - A Randomized Trial of Antiestrogen Therapy versus Combined Antiestrogen and Octreotide Lar Therapy in the Adjuvant Treatment of Breast Cancer in Post-Menopausal Women
Osteopontin (OPN) is a malignancy-associated glycoprotein that contributes functionally to tumour aggressiveness. In metastatic breast cancer, we previously demonstrated that elevated OPN in primary tumour and blood was associated with poor prognosis. The authors' hypothesis that OPN tumour expression would have independent prognostic value in early breast cancer was not supported by multivariate analysis of this study population. Plasma OPN levels in women with hormone responsive early breast cancer in the MA.14 trial were not elevated and there was no evidence for prognostic value of plasma OPN in this defined group of patients. However, the authors suggested their finding of elevated mean OPN plasma level around the time of recurrence warrants further study.
Bramwell VHC, Tuck AB, Chapman J-AW, Anborgh PH, Postenka CO, Al-Katib W, Shepherd LE, Han L, Wilson CF, Pritchard KI, Pollak MN, Chambers AF. Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial. Breast Cancer Research 16: 1-10, 2014.
About Canadian Cancer Trials Group MA.14 -- This trial was activated on September 24, 1996 and was closed to accrual on July 21, 2000 after reaching its accrual target of 650 patients. All patients completed or discontinued protocol-mandated treatment. The final analysis for clinical endpoints was performed in December 2007 and presented at ASCO 2008. There was no statistically significant difference in event-free survival between treatment arms. The collection of follow-up data for visits up to and including September 30, 2009 were continued in order to update major clinical endpoints. The final results of the trial were published in the Journal of Clinical Oncology in September 2011. Investigators found that octreotide-related changes in circulating IGF-1 and C-peptide levels were statistically significant. Octreotide did not add significant clinical benefit. High C-peptide levels (surrogate for insulin secretion rate) and high BMI were associated with poor outcome.
Pritchard KI, Shepherd LE, Chapman JA, Norris BD, Cantin J, Goss PE, Dent SF, Walde D, Vandenberg TA, Findlay B, O'Reilly SE, Wilson CF, Han L, Piura E, Whelan TJ, Pollak MN. Randomized Trial of Tamoxifen Versus Combined Tamoxifen and Octreotide LAR Therapy in the Adjuvant Treatment of Early-Stage Breast Cancer in Postmenopausal Women: Canadian Cancer Trials Group MA.14
Journal of Clinical Oncology: 29 (29): 3869 - 3876, 2011.