BIT-2

Ospedale San Raffaele

Via Olgettina, 60, Milano, Italy, 20133

Oncologia Medica, Ospedale San Raffaele , +39 02 26437644, cereda.stefano@hsr.it

Oncologia Medica, Ospedale San Raffaele, +39 02 26437644, cereda.stefano@hsr.it

No

No

No

Final

17 Dec 2015

Yes

06 May 2015

Yes

06 May 2015

Yes

Assessment of the therapeutic activity of capecitabine alone or in combination with mitomycin C in terms of progression-free survival rate at 6 months from treatment start in patients with advanced/metastatic biliary adenocarcinoma in progression after gemcitabine and platinum compounds.

Throughout the study, investigators prescribed any concomitant medication or treatment deemed necessary to provide adequate supportive care, as per protocol instructions, including therapeutic use of hematopoietic colony growth factors (granulocyte colony-stimulating factor [G-CSF]) and use of erythropoietin. Dose adjustment and dose delay were foreseen in case of hematological and non hematological toxicity.

04 Oct 2011

No

No

Italy: 57

57

57

0

0

0

0

0

0

22

35

0

Overall Trial (overall period)

Randomised - controlled

Yes

Capecitabine

Film-coated tablet

Oral use

2000 mg/m2, Day 1-14 of a 3-week cycle divided in two doses taken with food.

Mytomicin C

Powder for solution for infusion

Intravenous use

Patients were treated with IV infusion mitomycin C 6 mg/m2 on Day 1 of a 3-week cycle.

Capecitabine

Film-coated tablet

Oral use

2000 mg/m2, Day 1-14 of a 3-week cycle divided in two doses taken with food

Arm A

Arm B

Arm A

Arm B

Patients Evaluable for Efficacy Analysis

This is the patient population for the primary efficacy analysis of PFS-6 rate and consists of all eligible and treated patients who fulfil the following additional conditions: • The patient has baseline tumor/oncologic assessment. • The patient has received at least the first treatment cycle. • The patient doesn’t die within the first 3 weeks of treatment, thus preventing any benefit from the therapy. In case that the patient has not progressed or died before the 6 month tumour assessment and missed it, s/he will be classified as • failure, if at the following assessment s/he is rated as PD or there is no further information or dies without a re-assessment. • response, if at the following assessment s/he is SD or better If deemed of clinical interest, patient disposition, baseline characteristics and treatment exposure will be presented also in this population.

The PFS-6 rate, is calculated as the proportion of evaluable patients known to be alive and progression-free at ≥ 6 months since study treatment start out of the total number of evaluable patients. If 8 or more responses is achieved out of first 26 evaluable patients it is concluded that the regimen(s) deserve further exploration. Supportive analyses of the primary endpoint include the estimation of the PFS-6 rate together with its exact, two-tail, 95% confidence interval and the estimation of the PFS curve by the Kaplan-Meier method in both the evaluable and the treated patient population.

Primary

At six months from treatment start.

Progression-free survival is calculated as the time from the treatment start to the date of first documentation of objective progression or of death due to any cause, whichever comes first. Subjects who have not progressed while on study and have not died while on study are censored at the last evaluable radiographic assessment date.

Secondary

From treatment start to progression disease or death.

Objective Response Rate is the relative frequency of either a complete or partial response while on study; subjects prematurely discontinuing without a post-baseline tumour response assessment or subjects with an observed complete or partial response that is not confirmed are considered non-responders. Point and 95% confidence interval estimates are calculated for the objective tumor response rate. The analysis is performed in the evaluable and in the treated patient populations. The estimates of the rates of unconfirmed tumor objective responses ia also provided and considered as supportive.

Secondary

From randomization to first documentation of objective progression.

Overall Survival (OS) is the time from the date of randomization to the date of death from any cause. Subjects who are known to be alive or for whom a date of death is unknown, are censored on the later of the date of the last study assessment or last known telephone contact.

Secondary

From the randomization to death from any cause.

Disease Control Rate is the relative frequency of confirmed objective responses and long lasting (SD≥ 6 months) stabilizations measured from the date of randomization to the date of first documentation of objective progression. Point and 95% confidence interval estimates are calculated for the disease control rate (confirmed CRs / PRs and SD >= 6 weeks). The analysis are performed in the evaluable and in the treated patient populations.

Secondary

From randomization to first documentation of objective progression.

Before treatment administration at baseline (baseline signs and symptoms), on treatment until the safety follow up visit (42 days after the last dose of study drug administration).

The adverse events (AEs) are coded by the Medical Dictionary for Regulatory Activities (MedDRA) and their severity graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. All SAEs and non-serious AEs are collected.

5.1

Arm A

Arm B