Sandostatin LAR and Axitinib vs Pbo in Pnts With Advanced Well-differentiated Non-pancreatic Neuroendocrine Carcinomas

Brief summary public domain (ClinicalTrials.gov)

Assess whether therapy with axitinib, a potent angiogenic inhibitor of the tyrosine kinase receptors of VEGF bioavailable by oral administration, is capable of improving PFS in patients with advanced G1-G2 NETs of nonpancreatic origin with progressive disease documented in the 12 months prior to entering the study.

Detailed description public domain (ClinicalTrials.gov)

Phase II/III, prospective, multicenter, randomized (1:1), double-blind study to evaluate the efficacy and tolerability of axitinib in patients diagnosed with advanced G1-G2 neuroendocrine tumors (WHO 2010) of nonpancreatic origin that have presented documented disease progression in the 12 months prior to entering the study. In the first part of the study (Phase II), 105 patients were enrolled. The second part of the study is the expansion to Phase III, which is expected to include 148 additional patients. Patients will be randomized to receive Sandostatin LAR with axitinib or Sandostatin LAR with placebo until disease progression or unacceptable toxicity occurs. Randomization will be stratified by the time from diagnosis to enrollment in the study (more vs less than or equal to 12 months), the origin of the primary tumor (gastrointestinal tract vs non-gastrointestinal tract \[lung or other sites\]) and ki-67 (\< 5% vs \> 5%).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Efficacy of Axitinib in Terms of PFS (Investigator Assessment) [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 25 months]. Median, months (95% Confidence Interval). Axitinib + Sandostatin LAR (n=126): 17.2 (13.6 to 24.7); Placebo + Sandostatin LAR (n=130): 13.1 (10.9 to 18.6). Analysis, Axitinib + Sandostatin LAR vs Placebo + Sandostatin LAR: Cox Proportional Hazard 0.86 (95% CI 0.65 to 1.15); p=0.324; Regression, Cox; superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Objective Response Rate (ORR) (Investigator Assessment) [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 25 months]. Count Of Participants, Participants. Complete response: Axitinib + Sandostatin LAR (n=126): 2; Placebo + Sandostatin LAR (n=130): 1. Partial response: Axitinib + Sandostatin LAR (n=126): 20; Placebo + Sandostatin LAR (n=130): 5. Stable disease: Axitinib + Sandostatin LAR (n=126): 87; Placebo + Sandostatin LAR (n=130): 96. Progressive disease: Axitinib + Sandostatin LAR (n=126): 9; Placebo + Sandostatin LAR (n=130): 25. Not evaluable: Axitinib + Sandostatin LAR (n=126): 8; Placebo + Sandostatin LAR (n=130): 3. Analysis, Axitinib + Sandostatin LAR vs Placebo + Sandostatin LAR: p=0.007; Chi-squared, Corrected; superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Biochemical Response (5-OH-indoleacetic Acid and Chromogranin A) [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 25 months]. Count Of Participants, Participants. CgA response / Response: Axitinib + Sandostatin LAR (n=69): 31; Placebo + Sandostatin LAR (n=72): 27. CgA response / No response: Axitinib + Sandostatin LAR (n=69): 38; Placebo + Sandostatin LAR (n=72): 45. 5-HIAA response / Response: Axitinib + Sandostatin LAR (n=69): 19; Placebo + Sandostatin LAR (n=72): 16. 5-HIAA response / No response: Axitinib + Sandostatin LAR (n=69): 29; Placebo + Sandostatin LAR (n=72): 30. Analysis, Axitinib + Sandostatin LAR vs Placebo + Sandostatin LAR: p=0.407; Fisher Exact; superiority. Analysis, Axitinib + Sandostatin LAR vs Placebo + Sandostatin LAR: p=0.630; Fisher Exact; superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Safety and Tolerability of Axitinib (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE], Version 4.0) [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 25 months]. Count Of Participants, Participants. Any grade AEs / Yes, reported events: Axitinib + Sandostatin LAR (n=125): 121; Placebo + Sandostatin LAR (n=130): 124. Any grade AEs / No, no events reported: Axitinib + Sandostatin LAR (n=125): 4; Placebo + Sandostatin LAR (n=130): 6. SAEs / Yes, reported events: Axitinib + Sandostatin LAR (n=125): 48; Placebo + Sandostatin LAR (n=130): 30. SAEs / No, no events reported: Axitinib + Sandostatin LAR (n=125): 77; Placebo + Sandostatin LAR (n=130): 100. Toxicities requiring end of treatment / Yes, reported events: Axitinib + Sandostatin LAR (n=125): 23; Placebo + Sandostatin LAR (n=130): 4. Toxicities requiring end of treatment / No, no events reported: Axitinib + Sandostatin LAR (n=125): 102; Placebo + Sandostatin LAR (n=130): 126. Toxicities requiring treatment temporary interruption / Yes, reported events: Axitinib + Sandostatin LAR (n=125): 76; Placebo + Sandostatin LAR (n=130): 55. Toxicities requiring treatment temporary interruption / No, no events reported: Axitinib + Sandostatin LAR (n=125): 49; Placebo + Sandostatin LAR (n=130): 75. Toxicities requiring dose reductions / Yes, reported events: Axitinib + Sandostatin LAR (n=125): 44; Placebo + Sandostatin LAR (n=130): 10. Toxicities requiring dose reductions / No, no events reported: Axitinib + Sandostatin LAR (n=125): 81; Placebo + Sandostatin LAR (n=130): 120.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Efficacy of Axitinib in Terms of PFS (Central Blinded Assessment) [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 25 months]. Median, months (95% Confidence Interval). Axitinib + Sandostatin LAR (n=126): 16.6 (13.5 to 24.2); Placebo + Sandostatin LAR (n=130): 9.9 (8.2 to 13.9). Analysis, Axitinib + Sandostatin LAR vs Placebo + Sandostatin LAR: Cox Proportional Hazard 0.71 (95% CI 0.54 to 0.94); p=0.017; Regression, Cox; superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Objective Response Rate (ORR) (Central Blinded Assessment) [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 25 months]. Count Of Participants, Participants. Complete response: Axitinib + Sandostatin LAR (n=117): 2; Placebo + Sandostatin LAR (n=126): 0. Partial response: Axitinib + Sandostatin LAR (n=117): 13; Placebo + Sandostatin LAR (n=126): 4. Stable disease: Axitinib + Sandostatin LAR (n=117): 98; Placebo + Sandostatin LAR (n=126): 109. Progressive disease: Axitinib + Sandostatin LAR (n=117): 1; Placebo + Sandostatin LAR (n=126): 12. Not evaluable: Axitinib + Sandostatin LAR (n=117): 3; Placebo + Sandostatin LAR (n=126): 1. Analysis, Axitinib + Sandostatin LAR vs Placebo + Sandostatin LAR: p=0.007; Chi-squared, Corrected; superiority.