Clinical trial NCT01220128
Conditions: Neoplasms, Breast
Keywords: WT1 neoadjuvant tumor antigen immunotherapy breast cancer adult
Sponsor: GlaxoSmithKline
Start date: 2011-04-11; Completion date: 2014-11-14
Enrollment: 66 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the safety, immunogenicity and clinical activity of a new WT1 anti-cancer immunotherapy in patients with WT1-positive Stage II or III breast cancer. The treatment will be given before surgery in combination with standard therapy.

Detailed description:
The study will be conducted in two consecutive segments (Phase I and Phase II), each with specific objectives. Active follow-up will be for three years.

Patients in this study will be allocated to cohorts as below. Cohort A will include postmenopausal patients with hormone receptor-positive breast cancer who receive aromatase inhibitor (AI) as neoadjuvant therapy concurrently with administration of 6 or 8 doses of WT1 anti-cancer immunotherapy (WT1 ASCI)/placebo starting on Day 0. AI treatment will be administered daily for duration of either 18 (if 6 doses of WT1 ASCI/placebo) or 24 weeks (if 8 doses of WT1 ASCI/placebo).

Cohort B will include breast cancer patients who will receive neoadjuvant chemotherapy concurrently with administration of WT1 ASCI/placebo starting on Day 0. Neoadjuvant chemotherapy in Cohort B will consist either 1) if 6 doses of WT1 ASCI/placebo: 6 cycle-treatment chemotherapy regimens consist of 6, three-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI/placebo: 8 cycle-treatment regimens consisting of 4 three-weekly cycles of anthracycline-based therapy followed by 4 three-weekly or 12-weekly taxane administrations without trastuzumab.

Cohort C will include patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who will receive neoadjuvant trastuzumab (Herceptin) therapy combined with chemotherapy concurrently with administration of WT1 ASCI/placebo starting on Day 0. Neoadjuvant chemotherapy in Cohort C will consist either 1) if 6 doses of WT1 ASCI/placebo: 6 cycle-treatment chemotherapy regimens consist of 6, three-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI/placebo: 8 cycle-treatment regimens consisting of 4 three-weekly cycles of anthracycline-based therapy followed by 4 three-weekly or 12-weekly taxane administrations with trastuzumab.

Cohorts D and E will include patients with hormone receptor-positive and HER2 non-overexpressing breast cancer who will receive neoadjuvant chemotherapy. For patients in these Cohorts D and E, WT1 ASCI/placebo (placebo applicable only for Cohort E patients) will be administered on Day 14 of each three-weekly cycle of chemotherapy. Neoadjuvant chemotherapy in Cohorts D and E will consist either 1) if 6 doses of WT1 ASCI/placebo: 6 cycle-treatment chemotherapy regimens consist of 6, three-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI/placebo: 8 cycle-treatment regimens consisting of 4 three-weekly cycles of anthracycline-based therapy followed by 4 three-weekly taxane administrations without trastuzumab. Enrolment in Cohort E will be conditional on the absence of a safety signal and on the adequate induction of an immune response by the WT1 ASCI in Cohort D (defined as \>= 40% response rate based on post-Dose 4 anti-WT1 antibody responses in at least six patients). If this criterion is met, 60 patients (40 receiving WT1 ASCI and 20 placebo) with identical eligibility criteria will be enrolled into Cohort E. In case no adequate safety and/or immunogenicity will be obtained in Cohort D, recruitment in Cohort E will not be initiated.

The protocol has been updated following Protocol Amendment 4, April 2013, leading to the update of the study design.

Arms: arm 1: This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule. arm 2: This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule. arm 3: This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule. arm 4: This group included breast cancer patients who received placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule. arm 5: This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of GSK2302024A, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule. arm 6: This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule. arm 7: This group included patients with hormone receptor-positive and HER2 non-overexpressing breast cancer, who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.
Interventions: intervention 1: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A intervention 2: Placebo intervention 3: Aromatase inhibitor intervention 4: 5-Fluorouracil intervention 5: Carboplatin AUC intervention 6: Cyclophosphamide intervention 7: Docetaxel intervention 8: Doxorubicin intervention 9: Epirubicin intervention 10: Paclitaxel intervention 11: Trastuzumab
Intervention descriptions: intervention 1: 6 or 8 injections at 3 weeks apart, injected intramuscularly in the deltoid or lateral region of the thigh. intervention 2: 6 or 8 doses at 3 weeks apart of sucrose/mannitol-based formulation reconstituted with an oil-in-water emulsion, injected intramuscularly in the deltoid or lateral region of the thigh. intervention 3: This treatment consisted of any aromatase inhibitor (e.g. letrozole or exemestane), administered intravenously in Cohort A Groups daily for either 18 (if 6 doses of WT1 ASCI/placebo) or 24 weeks (if 8 doses of WT1 ASCI/placebo). intervention 4: Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses at 3 weeks apart, and for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle. intervention 5: Administered intravenously in Cohort C Groups in 6 doses at 3 weeks apart, on the same day as WT1 ASCI/placebo administration (Day 1 of each cycle). intervention 6: Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses in Cohort C Groups and 6 doses 3 weeks apart in Cohorts A Placebo, B and D Groups, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle. intervention 7: Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle. intervention 8: Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 6 doses 3 weeks apart (Cohort C patients with this schedule did not receive this treatment), while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle. intervention 9: Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle. intervention 10: Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: only in the 8 WT1 ASCI-dose schedule patients received 4 at 3 weeks apart or 12 weekly doses. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle. intervention 11: Administered intravenously in Cohort C Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohort B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

Protocol documents: