Background: The study design and nature of oncology phase 1 clinical trials create a uniquely vulnerable patient population yet little research has been conducted to identify the added burden these trials create for both cancer patients and their caregiver(s). Objective: Examining the perceptions and needs of patients and their caregivers participating in phase 1 oncology clinical trials, the investigators tested the hypothesis that the caregiver will exhibit a higher level of burden and/or distress than the patient. Method: A mixed-methods exploratory process utilizing patient and caregiver interviews and quality-of-life questionnaires was used to assess the psychosocial burdens associated with oncology clinical trial participation. A qualitative and quantitative analysis of the responses were 8 performed. Result: Both patients and caregivers reported similar themes identifying the burdens and benefits related to phase 1 clinical trial participation. However, the caregivers’ expressed burden exceeded that of the patients’ validating the study’s hypothesis. Conclusion: The need for ongoing additional support services for not only the patient but also the caregiver was identified.

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197 Background: Novel agents capable of blocking AR ligand independent pathways responsible for the development of CRPC are needed. IGF-1R and its ligands (IGF-1/IGF-2) play a key role in regulating growth, resistance to apoptosis, and invasion in PCa. IGF-1R is overexpressed in PCa and mediates resistance to ADT. OSI-906 is a small molecule potent dual inhibitor of IGF-1R and insulin receptor TK activity. To determine the activity of OSI-906 in men with CRPC a Simon two-staged phase II study was conducted. Methods: Men with asymptomatic or mildly symptomatic Met CRPC were eligible. ECOG 0-1, adequate organ function, and no prior chemotherapy for CRPC were required. Pts received OSI-906 at 150mg orally twice daily on a 28-day cycle. Endpoints included PSA response at 12 wks, safety, RECIST-defined response, time to PSA progression, and OS. Correlative studies explored the impact of OSI-906 on AR signaling (androstenedione, DHEA, DHEA-sulfate, p-IGF-1R, p-IR), markers of PD (TGF-b1, IL-6, TNF-a, MCP-1), and CTC and CECs. Results: To date 18 pts have enrolled and completed 12 wks of therapy. Median age 68 (55-78); Median pre-treatment PSA was 55.23 (range 2.46-277.60); 41% of pts had bone-only disease, 29% soft-tissue only and 29% had both. Although transient PSA declines were noted, 17/18 pts discontinued therapy sec PSA progression. RECIST-defined SD was observed in 8 pts. Pts received a median of 3 cycles of therapy (range 2-6+). Most common G1/2 AEs included AST/ALT changes observed in 41 and 18% of patients respectively, fatigue (59%); prolong QT interval (35%) and nausea/vomiting (35%). No significant change in the number of CTC and CEC counts was observed. An association between pre-treatment PSA and pre-treatment CTC was observed (Spearman r=0.49, p=.04). No correlation between CTC changes and PSA progression was observed .Evaluation of other molecular markers of PD is underway. Conclusions: Treatment with OSI-906 is safe. No PSA responses or changes in CTC/CECs were noted. Markers of PD might help elucidate potential mechanisms of escape to this alternative pathway in CRPC. OSI-906 plus an AA might provide synergistic activity in this setting. Clinical trial information: NCT01533246.

e16022 Background: AR ligand independent pathways are responsible for the development of CRPC. IGF-1R and its ligands (IGF-1/IGF-2) play a key role in regulating growth, resistance to apoptosis, and invasion in PCa. IGF-1R is overexpressed in PCa and mediates resistance to ADT. Linsitinib is a small molecule potent dual inhibitor of IGF-1R and insulin receptor TK activity. To determine the activity of linsitinib in men with CRPC a Simon two-stage phase II study was conducted. Methods: Men with asymptomatic or mildly symptomatic Met CRPC were eligible. ECOG 0-1, adequate organ function, and no prior chemotherapy for CRPC were required. Pts received linsitinib at 150mg orally twice daily on a 28-day cycle. Endpoints included PSA response at 12 wks, safety, RECIST-defined response, time to PSA progression, and OS. Correlative studies explored the impact of linsitinib on AR signaling (androstenedione, DHEA, DHEA-sulfate, p-IGF-1R, p-IR), markers of PD (TGF-b1, IL-6, TNF-a, MCP-1), and CTC and CECs. Results: Eighteen pts were enrolled and completed 12 wks of therapy. Median age 68 (55-78); Median pre-treatment PSA was 55.23 (range 2.46-277.60); 41% of pts had bone-only disease, 29% soft-tissue only and 29% had both. Although transient PSA declines were noted (8/18), seventeen pts discontinued therapy sec PSA progression. RECIST-defined SD was observed in 8 pts. Pts received a median of 3 cycles of therapy (range 2-6+). Most common G1/2 AEs included AST/ALT changes observed in 41 and 18% of patients respectively, fatigue (59%); prolonged QT interval (35%) and nausea/vomiting (35%). No significant change in the number of CTC and CEC counts was observed. An association between pre-treatment PSA and pre-treatment CTC was observed (Spearman r=0.49, p=.04). No correlation between CTC changes and PSA progression was observed .Evaluation of other molecular markers of PD is underway. Conclusions: Treatment with linsitinib is safe however no PCa activity was seen. No changes in CTC/CECs were noted. Markers of PD might help elucidate potential mechanisms of escape to this alternative pathway in CRPC. Linsitinib plus an AA might provide synergistic activity in this setting. Clinical trial information: NCT01533246.

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