Here is the design of a clinical trial:

Official Title: A Phase II Trial Aiming to Assess the Safety and Activity of the Combination of Cabozantinib Plus Lanreotide in Gastroenteropancreatic (GEP) and Thoracic Neuroendocrine Tumor (NET): The LOLA Trial

Included conditions:
- Metastatic Well Differentiated Neuroendocrine Neoplasm
- Neuroendocrine Tumors

Study Armgroups:
- {'label': 'Cabozantinib+lanreotide', 'type': 'EXPERIMENTAL', 'description': 'Cabozantinib will be administered orally at a dose of 60 mg/day continuously in combination with Lanreotide 120 mg injection every 28 days. Both treatments will start the same day', 'interventionNames': ['Drug: Cabozantinib', 'Drug: Lanreotide']}

Interventions:
- {'type': 'DRUG', 'name': 'Cabozantinib', 'description': 'Cabozantinib will be administered orally at a dose of 60 mg/day', 'armGroupLabels': ['Cabozantinib+lanreotide'], 'otherNames': ['Cabometyx']}
- {'type': 'DRUG', 'name': 'Lanreotide', 'description': 'Lanreotide will be administrated 120 mg injection every 28 days', 'armGroupLabels': ['Cabozantinib+lanreotide'], 'otherNames': ['IPSTYL']}

Primary Outcomes:
- {'measure': 'Objective Response Rate (ORR)', 'description': 'according to RECIST, v1.1 defined as complete response or partial response after treatment administration', 'timeFrame': '42 months'}
- {'measure': 'Primary Safety Endpoint', 'description': 'Adverse Events (AE) grade 3-5 according to NCI-CTCAE v5.0 grade', 'timeFrame': '42 months'}

Please estimate the sample size based on the assumption: 
Nominal type I error = 0.05, nominal type II error = 0.20. Considering a drop-out rate of 5%. Thresholds to identify significant level at 5% and exact binomial test’s power will be determined based on the real number of patients to be analyzed (e.g., 0 out of 20 patients [test’s power: 36%], 3 out of 39 patients [test’s power: 87%], 6 out of 58 patients [test’s power: 97%]).
Sample size and statistical design
        The statistical design is adaptive, according to three sequential stages (see the study flow-chart depicted in Fig.Â 2).Fig. 2Study design N: number; pNETs: pancreatic neuroendocrine tumors; ORR: Overall response rate; OS: overall survival; PFS: progression-free survival; WD: well-differentiated
        Two cohorts of patients will be enrolled in the study according to different histotypes: the first cohort includes pNETs; the second cohort includes carcinoids (i.e. small intestine NETs, stomach NETs, colon and rectum NETs, typical and atypical lung and thymus NETs) and NETs of unknown origin. Enrolment in the pancreatic and carcinoid arms will be competitive in the first stage (i.e. run-in stage).
        I stage. The primary objective of I stage is to find the optimal dose of cabozantinib in combination with lanreotide and to evaluate the safety and the tolerability of the combination. Starting dose of cabozantinib is 60Â mg daily plus lanreotide 120Â mg every 28Â days. No more than 7 patients will be enrolled in the I stage. If G3-5 adverse events (AEs)âexcluded not clinically relevant laboratory abnormalities according to NCI-CTCAE version 5.0 or clinically manageable and reversible G3 AEs within 7Â days of onsetâare observed in more than one patient out of the first seven enrolled patients, cabozantinib starting dose of 60Â mg will be considered too toxic and ruled out (H0: % grade 3â5 toxicitiesââ¤â5%; nominal p-value: 0.05; actual p-value: 0.044) and 40Â mg will be chosen as starting dose of cabozantinib in the subsequent stage. Otherwise, 60Â mg will be chosen as starting dose of cabozantinib in the subsequent stage. An interim safety analysis will be performed when 7 patients will be observed on treatment for at least 8Â weeks.
        In order to preserve internal validity, outcomesâ assessment will be re-started de novo in the II stage (i.e. I and II stages are distinct phases of an operationally seamless, not inferentially seamless design).
        II-III stage. In stages II-III the optimal Simon two-stage design will be used for both cohorts [35]. The primary endpoint of the II and III stages is ORR according to RECIST version 1.1. Co-primary endpoint will be the evaluation of the percentage of G 3â5 toxicities according to NCI-CTCAE version 5.0. Secondary endpoints will be PFS and OS.
        The uninteresting antitumor activity (H0) is fixed in ORRââ¤â5%. The useful antitumor activity to be detected (H1) is fixed in ORRââ¥â20%. For both arms (pNET and carcinoids), 10 patients will be accrued in the stage II. If no responses are observed in these 10 patients, the arm will be stopped (nominal type II errorâ=â0.20). Otherwise, other 19 patients will be accrued in stage III, for a total of 29 patients. The null hypothesis will be rejected if 4 or more responses are observed in 29 eligible patients (nominal type I errorâ=â0.05). Considering a drop-out rate of 5% (i.e. eligible patients without the assessment of objective response) the maximum number of enrolled patients will be 69 (including the 7 patients included in the interim analysis after stage I).
        Regarding the safety co-primary endpoint, the null hypothesis to be rejected is a percentage of AEs greater or equal to 20% (i.e. H0:ââ¥â20%, nominal type I errorâ=â0.05) against an alternative hypothesis H1:ââ¤â5%. Because the statistical design is adaptive (i.e. a couple of Simonâs two stage designs are planned after the first run-in stage), the total number of patients that could be analyzed for safety is uncertain prior to study execution. It will be 20 patients if both arms stop at stage II, 39 patients if only one arm stops at stage II and 58 patients if both arms participate to stage III. Thresholds to identify significant level at 5% and exact binomial testâs power will be determined based on the real number of patients to be analyzed (i.e. 0 out of 20 patients [testâs power: 36%], 3 out of 39 patients [testâs power: 87%]; 6 out of 58 patients [testâs power: 97%] are the maximum number of patients with observed G3-G5 AEs to reject H0:ââ¥â20% at a 5% significant level). Patients who did not receive treatment for any cause or severely violated protocol inclusion/exclusion criteria will be excluded from the primary and secondary analyses of all stages.