Coleman 2014.

Methods	Open‐label multi‐centre phase II RCT with cross‐over (137 study locations in the USA). Recruitment from March 2010 to August 2011
Participants	129 women with histologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal carcinoma. Participants had to have recurrent, refractory, or progressive/persistent disease (following 1 prior platinum‐based course of chemotherapy for primary disease, and up to 3 additional courses of cytotoxic therapy for recurrent disease) that was measurable or, if not measurable by RECIST criteria, evaluable by imaging. Other inclusion criteria included a performance status of Zubrod 0 to 2 and adequate haematological, renal, liver, and cardiovascular function. Recent cancer (within 5 years from diagnosis for ovarian cancer) was an exclusion criterion, except preinvasive disease and early‐stage endometrial cancer. Study author confirmed that, to his knowledge, no participants had concurrent malignancies. Baseline characteristics Single‐agent docetaxel (D) Age ‐ median (range): 61.7 (32.6 to 80) Prior antiangiogenic therapy ‐ yes: 12 (18%) Prior antiangiogenic therapy ‐ no: 54 (82%) Prior treatment with platinum for recurrent disease: 34 (52%) Baseline CA‐125 ‐ median (range): 111 (1 to 6019) Docetaxel and vandetanib (D + V) Age ‐ median (range): 61.9 (34.3 to 82.5) Prior antiangiogenic therapy ‐ yes: 9 (14%) Prior antiangiogenic therapy ‐ no: 54 (86%) Prior treatment with platinum for recurrent disease: 28 (44%) Baseline CA‐125 ‐ median (range): 160 (5 to 4113)
Interventions	Intervention Docetaxel (75 mg/m² IV, day 1 only) with vandetanib (100 mg PO daily, days 1 to 21) (21‐day course, repeated until disease progression, unacceptable toxicity, or withdrawal of consent) Comparison Docetaxel (75 mg/m² IV, once every 21 days) (continued until disease progression, unacceptable toxicity, or withdrawal of consent) Note: participants randomised to single‐agent docetaxel were allowed to cross over to single‐agent vandetanib (100 mg PO daily) upon documented progression.
Outcomes	Primary Progression‐free survival (PFS) (HR 0.99, 95% CI 0.69 to 1.42; P = 0.49) Median time to progression: 3.5 months (D) vs 3 months (D + V) Secondary Overall survival (OS): HR 1.25, 80% CI 0.93 to 1.68; P = 0.83) Median survival: D = 18 months vs D + V = 14 months Number of deaths: D = 36; D + V = 41 Response (complete and partial): no complete responses. Partial response: D = 5/57 (9%) vs D + V = 6/52 (12%) PFS according to CA‐125 criteria: median 2.9 months (D) vs 2.8 months (D + V) (P = 0.44) Toxicity (G3 to 4) Febrile neutropaenia (G3 to 4): D = 0/64 vs D + V = 1/61 Anaemia (G3 to 4): D = 1/64 vs D + V = 2/61 Neutropaenia (G3 to 4): D = 32/64 vs D + V = 28 Fatigue (G3 to 4): D = 6/64 vs D + V = 5/61 Nausea and vomiting (G3 to 4): D = 5/64 vs D + V = 3/61 Rash (G3 to 4): D = 0/64 vs D + V = 6/61 Hypertension (any grade): D = 0/64 vs D + V = 8/61
Notes	ClinicalTrials.gov identifier: NCT00872989 This study was an ongoing trial in the original version of this review; results have since been published. Sponsorship source: Financial Support: R Coleman, A Sood. "This investigation was supported by the Marcus Foundation, the Investigator‐Sponsored Study Program of AstraZeneca, Wilmington, DE, and in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute US: DHHS: CA32102, CA38926, CA105409, CA35431, CA45560,CA20319, CA13612, CA46441, CA45808, CA45461,CA67575, CA58882, CA35128, CA37981, CA46282,CA35421, CA76132, CA58723, CA16385, and CA42777; as well as P50 CA083639, OCRP‐OC0931146, and the Blanton‐Davis Ovarian Cancer Research Program. A.K.S. is supported by the Betty Anne Asche Murray Distinguished Professorship. Research support to R.L.C.is by the Ann Rife Cox Chair in Gynecology". Country: United States of America Setting: multi‐centre study Author's name: Robert L. Coleman Institution: University of Texas, MD Anderson Cancer Center, Houston, TX, USA Email: rcoleman@mdanderson.org Address: MD Anderson Cancer Center, Department of Gynecologic Oncology & Reproductive Medicine, 1155 Herman Pressler Drive, CPB6.3271, Houston, TX 77030, USA
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "participants were randomised centrally 1:1 using a dynamic balancing algorithm with stratification"
Allocation concealment (selection bias)	Low risk	Comment: randomisation was performed centrally at the SWOG Statistical Center. Thus, it is unlikely that intervention allocations could have been foreseen in advance by those recruiting participants.
Blinding of participants and personnel (performance bias) Objective outcome measures (Overall Survival)	Low risk	Outcome unlikely to be affected by blinding
Blinding of participants and personnel (performance bias) Subjective outcome measures (PFS; Toxicity; QoL)	High risk	Open‐label study
Blinding of outcome assessment (detection bias) Objective outcome measures (overall survival)	Low risk	Outcome unlikely to be affected by blinding
Blinding of outcome assessment (detection bias) Subjective outcome measures (PFS, Toxicity, QoL)	High risk	Open‐label study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attritions/exclusions were well reported
Selective reporting (reporting bias)	Low risk	We compared reported outcomes to those intended (from the online protocol): the published paper covered the main planned primary outcomes from the protocol. Exploratory analyses, which had not been prespecified, were generally indicated as such, and these data were not extracted for the review.
Other bias	Unclear risk	Conflicts of interest of study authors are reported: one study author served as an uncompensated scientific advisor for other projects of the drug manufacturer; other study authors declare no conflicts.