a pilot, open-label study of 18f-fluciclatide pet/ct imaging in the evaluation of anti-angiogenic therapy in solid tumors

Conditions: Colon Cancer; Lung Cancer; Cervical Cancer; Renal Cell Carcinoma; Uterine Cancer

Summary: background: * fluciclatide is a small cyclic peptide containing the rgd tri-peptide, which preferentially binds with high affinity to alpha(v)beta(3) integrins, which are up-regulated in and may regulate angiogenesis. * \[18f\]fluciclatide is a new radiopharmaceutical developed for pet imaging * changes in \[18f\]fluciclatide uptake will be evaluated before and after treatment of patients with targeted antiangiogenic drugs objectives: primary * to determine tumor uptake and retention of \[18f\]fluciclatide before and after 1 cycle of treatment with targeted anti-angiogenic therapy * secondary * to assess the safety of multiple intravenous (iv) administrations of fluciclatide \[18f\] injection in subjects with solid tumors * to obtain preliminary data on the relationships between \[18f\]fluciclatide as a pharmacodynamic marker and standard of care imaging markers of clinical response (e.g. contrast-enhanced (ce) static computed tomography (ct), bone scintigraphy, fdg-pet), obtained as part of routine clinical follow-up as specified in the referring protocols, as well as any optional imaging performed eligibility: * patients greater than or equal to 18 years, with documented malignancy, and solid tumor greater than or equal to 1 cm outside of the liver, who are scheduled to enroll in an nci therapy protocol using one of the anti-angiogenic agents described in the full protocol * platelet count greater than 75,000 x 10(6)/l, hemoglobin greater than 9g/dl, prothrombin time (pt) and aptt less than 2 times normal limits. * the subject has not received any targeted anti-angiogenic agents within 60 days prior to pre-treatment (baseline) \[18f\]fluciclatide administration design: this study is intended to obtain preliminary data on the uptake and retention of \[18f\]fluciclatide before and after anti-angiogenic therapy. this will enable optimization of the imaging protocol, identification of the most relevant imaging parameters, and allow for calculation of the number patients required to power a larger study to assess the utility of pet imaging with \[18f\]fluciclatide as a pharmacodynamic biomarker in the context of targeted anti-angiogenic therapies. we expect to enroll 30 evaluable patients in this single center study. subjects will undergo at least two \[18f\]fluciclatide pet/ct imaging studies, one pre-therapy and one following completion of 1 cycle of chemotherapy. an optional early post-therapy (2-7 days post therapy commencement) \[18f\]fluciclatide pet/ct may be performed. the magnitude of \[18f\]fluciclatide uptake on the pre- and post- treatment pet/ct studies will be evaluated to determine if there is a measureable difference in uptake. data from the subject's referring therapy protocol will be reviewed for up to one year. an optional dce-mri scans of the target lesion may also be performed.

background: * fluciclatide is a small cyclic peptide containing the rgd tri-peptide, which preferentially binds with high affinity to alpha(v)beta(3) integrins, which are up-regulated in and may regulate angiogenesis. * \[18f\]fluciclatide is a new radiopharmaceutical developed for pet imaging * changes in \[18f\]fluciclatide uptake will be evaluated before and after treatment of patients with targeted antiangiogenic drugs objectives: primary * to determine tumor uptake and retention of \[18f\]fluciclatide before and after 1 cycle of treatment with targeted anti-angiogenic therapy * secondary * to assess the safety of multiple intravenous (iv) administrations of fluciclatide \[18f\] injection in subjects with solid tumors * to obtain preliminary data on the relationships between \[18f\]fluciclatide as a pharmacodynamic marker and standard of care imaging markers of clinical response (e.g. contrast-enhanced (ce) static computed tomography (ct), bone scintigraphy, fdg-pet), obtained as part of routine clinical follow-up as specified in the referring protocols, as well as any optional imaging performed eligibility: * patients greater than or equal to 18 years, with documented malignancy, and solid tumor greater than or equal to 1 cm outside of the liver, who are scheduled to enroll in an nci therapy protocol using one of the anti-angiogenic agents described in the full protocol * platelet count greater than 150,000 x 10(6)/l, hemoglobin greater than 9g/dl, prothrombin time (pt) and aptt less than 2 times normal limits. * the subject has not received any targeted anti-angiogenic agents within 60 days prior to pre-treatment (baseline) \[18f\]fluciclatide administration design: this study is intended to obtain preliminary data on the uptake and retention of \[18f\]fluciclatide before and after anti-angiogenic therapy. this will enable optimization of the imaging protocol, identification of the most relevant imaging parameters, and allow for calculation of the number patients required to power a larger study to assess the utility of pet imaging with \[18f\]fluciclatide as a pharmacodynamic biomarker in the context of targeted anti-angiogenic therapies. we expect to enroll 30 evaluable patients in this single center study. subjects will undergo at least two \[18f\]fluciclatide pet/ct imaging studies, one pre-therapy and one following completion of 1 cycle of chemotherapy. an optional early post-therapy (2-7 days post therapy commencement) \[18f\]fluciclatide pet/ct may be performed. the magnitude of \[18f\]fluciclatide uptake on the pre- and post- treatment pet/ct studies will be evaluated to determine if there is a measureable difference in uptake. data from the subject's referring therapy protocol will be reviewed for up to one year. an optional dce-mri scans of the target lesion may also be performed.

Eligibility criteria:
* inclusion criteria: * adult subjects (greater than or equal to18 years old), with documented malignancy, with at least one solid tumor greater than or equal to 1 cm in diameter (not within the liver), who are scheduled to enroll in an nci therapy protocol using one of the anti-angiogenic therapy agents (vandetanib, cediranib or bevacizumab) * the subject has a platelet count of 150,000 x 10(6)/l, hemoglobin value of greater than 9 g/dl, pt and an aptt less than 2 times normal limits. * the subject has a clinically acceptable medical history, physical examination and vital signs findings during the screening period (from less than 4 weeks before administration of fluciclatide (18f) injection); i.e. eastern cooperative oncology group (ecog) performance score of 0 to 2. * the subject has had no open surgical wounds in close proximity to the target lesion(s) within 10 days prior to study entry. * the subject has not had a biopsy of the target lesion within 7 days of pet/ct imaging. * the subject has not had radiation therapy to the region of the target lesion. * enrolling in the following nci anti-angiogenic therapy protocols: 08-c-0020 09-c-0192 07-c-0058 09-c-0019 exclusion criteria: * the subject is pregnant or lactating. * the subject is being treated with doses of heparin or warfarin resulting in elevation of pt or aptt greater than 2 times normal. * the subject has received any anti-angiogenic agent (e.g. bevacizumab, sorafenib, sunitinib) within 60 days prior to pre-treatment (baseline) \[18f\]fluciclatide pet imaging. this stipulation does not apply after the baseline \[18f\]fluciclatide pet imaging. * the subject has received another investigational medicinal product (imp) within 24 hours before or is scheduled to receive another imp within 24 hours after fluciclatide (18f) injection. * the subject has any contraindication to any of the study procedures, products used or its constituents (e.g. severe claustrophobia unrelieved by oral anxiolytics). * the subject is unable to lie still for 75 minutes. * the subject is known to have a history of hyper- or hypo-coagulation syndromes resulting in prolongation of bleeding parameters. such coagulopathies include but are not limited to von willebrand disease, protein c deficiency, protein s deficiency, hemophilia a/b/c, factor-v leiden, and bernard-soulier syndrome. * the subject has undergone a surgical procedure to the target lesion within 28 days prior to baseline \[18f\]fluciclatide administration or is scheduled to undergo a surgical procedure between the baseline and post 1-cycle \[18f\]fluciclatide pet/ct. * the subject has only bone metastasis additional inclusion criteria for subjects undergoing optional mr: -serum creatinine within 2 weeks prior to mri less than or equal to 1.8mg/dl and estimated glomerular filtration rate (egfr) must be greater than 30 ml/min/1.73m(2). additional exclusion criteria for subjects undergoing optional mr: * the subject has known allergy to gadolinium * the subject has contraindications to mri: * subjects must weigh less than 136 kg (weight limit for scanner table). * subjects cannot have pacemakers, cerebral aneurysm clips, shrapnel injury, or other implanted electronic devices or metal not compatible with mri.

Keywords: pet imaging (18f)fluciclatide anti-angiogenic therapies solid tumors