Here is the design of a clinical trial:

Official Title: Neo-adjuvant Chemotherapy Combined With Stereotactic Body Radiotherapy to the Primary Tumour +/- Durvalumab, +/- Oleclumab in Luminal B Breast Cancer: a Phase ll Randomised Trial

Included conditions:
- Luminal B

Study Armgroups:
- {'label': 'Chemotherapy and radiotherapy', 'type': 'EXPERIMENTAL', 'description': 'The combination of weekly paclitaxel 80 mg/m² IV followed by q2w dose-dense doxorubicin-cyclophosphamide (ddAC) (60 mg/m² doxorubicin IV and 600 mg/m² cyclophosphamide IV) and pre-operative radiation therapy on the primary tumour (3x8 Gy).', 'interventionNames': ['Radiation: Stereotactic Body Radiotherapy']}
- {'label': 'Chemotherapy and pre-operative radiotherapy plus durvalumab', 'type': 'EXPERIMENTAL', 'description': 'The combination of weekly paclitaxel 80 mg/m² IV followed by q2w dose-dense doxorubicin-cyclophosphamide (ddAC) (60 mg/m² doxorubicin IV and 600 mg/m² cyclophosphamide IV) and pre-operative radiation therapy on the primary tumour (3x8 Gy) with the addition of the anti-PD-L1 antibody durvalumab IV 1500 mg q4w.', 'interventionNames': ['Drug: Durvalumab', 'Radiation: Stereotactic Body Radiotherapy']}
- {'label': 'Chemotherapy & pre-op radiotherapy + durvalumab + oleclumab', 'type': 'EXPERIMENTAL', 'description': 'The combination of weekly paclitaxel 80 mg/m² IV followed by q2w dose-dense doxorubicin-cyclophosphamide (ddAC) (60 mg/m² doxorubicin IV and 600 mg/m² cyclophosphamide IV) and pre-operative radiation therapy on the primary tumour (3x8 Gy) with the addition of the anti-PD-L1 antibody durvalumab IV 1500 mg q4w and the addition of the anti-CD73 antibody oleclumab IV 3000 mg q2w for 4 administrations, followed by q4w for 3 administrations.', 'interventionNames': ['Drug: Durvalumab', 'Radiation: Stereotactic Body Radiotherapy', 'Drug: Oleclumab']}

Interventions:
- {'type': 'DRUG', 'name': 'Durvalumab', 'description': 'an anti PD-L1 intravenous administration at 1500 mg every 4 weeks for 19 weeks.', 'armGroupLabels': ['Chemotherapy & pre-op radiotherapy + durvalumab + oleclumab', 'Chemotherapy and pre-operative radiotherapy plus durvalumab'], 'otherNames': ['MEDI4736']}
- {'type': 'RADIATION', 'name': 'Stereotactic Body Radiotherapy', 'description': 'Pre-operative radiation therapy (boost dose) 3x8 Gy on the primary tumour at week 5 given in 3 fractions. The 3 fractions will be spread at the minimum over 3 days and at the maximum over 6 days.', 'armGroupLabels': ['Chemotherapy & pre-op radiotherapy + durvalumab + oleclumab', 'Chemotherapy and pre-operative radiotherapy plus durvalumab', 'Chemotherapy and radiotherapy'], 'otherNames': ['SBRT']}
- {'type': 'DRUG', 'name': 'Oleclumab', 'description': 'an anti-CD73 intravenous administration at 3000 mg every 2 weeks for the first 4 administrations then every 4 weeks for the last 3 administrations.', 'armGroupLabels': ['Chemotherapy & pre-op radiotherapy + durvalumab + oleclumab'], 'otherNames': ['MEDI9447']}

Primary Outcomes:
- {'measure': 'Safety Run-in: Evaluation of the immune related or radiation therapy related toxicity of special interest', 'description': 'Immune related or radiation therapy related toxicity of special interest are identifitied as:\n\n* Any Grade 4 immune-related AE\n* Any ≥ Grade 3 colitis\n* Any ≥ Grade 3 renal failure/nephritis\n* Any ≥ Grade 3 non-infectious pneumonitis irrespective of duration\n* Any Grade 3 immune-related AE, excluding colitis, renal failure/nephritis and pneumonitis, that does not downgrade to ≤ Grade 2 within 3 days after onset of the event despite maximal medical supportive care including systemic corticosteroids or does not downgrade to ≤ Grade 1 or baseline within 14 days\n* Liver transaminase elevation ≥ 5 ULN or total bilirubin \\> 3 × ULN will be considered a DLT regardless of duration or reversibility\n* Any increase in AST or ALT \\> 3 × ULN and concurrent increase in total bilirubin \\> 2 × ULN', 'timeFrame': '7 months'}
- {'measure': 'Safety Run-in: Evaluation of the feasibility of the primary surgery', 'description': 'Feasibility of performing surgery within 6 weeks after the last neo-adjuvant treatment. This would indicate that there were no significant delays or toxicities that would results in surgery being delayed.', 'timeFrame': '7 months'}
- {'measure': 'Phase II: Demonstration of the tumour response in arms 2 or 3 versus arm 1', 'description': 'To demonstrate improved tumour response of the primary tumour and nodal metastases in arms 2 or 3 versus arm 1 using residual cancer burden (RCB 0-1 vs. RCB 2-3) at time of surgery.', 'timeFrame': '24 months'}

Please estimate the sample size based on the assumption: 
A two-sided alpha level of 2.5% and a power of 80% have been targeted. No continuity correction was used, and a pooled estimate of variance was chosen. A 5% non-evaluability rate, a 5% non-eligibility rate, and a 20% screening failure rate were considered.
Sample size
          Six patients will be included in the safety run-in. In the phase II part, patients will be randomized in a 1:1:1 ratio between 3 arms and the primary endpoint that will be measured on those patients is the binary achievement of RCB 0â1 versus RCB 2â3. The trial is designed to compare arm 2 to arm 1 as well as arm 3 to arm 1. The trial is not powered to compare arms 2 and 3 and no specific hypothesis is formulated for that comparison. It is expected that arm 1 will achieve an RCB 0â1 rate of 15% and the experimental treatment arms will be considered of interest for further investigation if this rate can be increased to 45%. This estimation for arms 2 and 3 are based on the first results of the I-SPY 2 trial (2017): the addition of immune checkpoint blockade (ICB) to standard NACT increased pCR from 13.6 to 34.2% [16]. Taking into account the addition of radiation therapy and the use of RCB 0â1 as endpoint, we hypothesize an increase in RCB 0â1 rates from 15 to 45% in either arm 2 or 3. There will be then two hypotheses testing, both aiming to reject the null hypothesis of equality of the RCB 0â1 rates between the control and in the experimental arms. A two-sided alpha level of 2.5% will be used and a power of 80% has been targeted in case the true RCB rate in either arm 2 or arm 3 is at least 45%. The alpha level of 2.5% was chosen to adjust for multiplicity. No continuity correction was used, and a pooled estimate of variance was chosen to estimate requested sample size. Sample size calculations are summarized in TableÂ 2. With those assumptions, 44 evaluable patients per arm are needed, i.e. a total of 132 patients. In order to take into account a 5% non-evaluability rate and a 5% non-eligibility rate, this sample size will be increased to 147 patients to be randomized. Assuming 20% screening failures (taking into account MammaPrint patients that are screened as MammaPrint genomic low risk), 184 patients will have to be screened.
Table 2Statistical sample size calculationSafety run-inNumbers of subjects needed6 subjectsPhase II trialâPrimary endpoint achievement RCB 0/1 vs. RCB 2/3Standard arm: 15%Experimental arms: 45%Hypothesis: increase in RCB 0/1 rates from 15 to 45% in either arm 2 or 3.âAlpha level (two-sided)2.5%âPower80%Number of subjects neededâ1:1:1 randomization44 subjects per arm, total of 132 subjectsIncrease for:â¢ 5% ineligible after randomisationAdd 15 subjectsâ¢ 5% unevaluable subjects147 randomised subjectsIncrease for 20% ineligible after screening (MammaPrint genomic low risk).Add 37 subjects.Total for phase 2 trial184 subjects screenedTotal evaluable subjects (safety run-inâ+âphase II)136 subjects