Efficacy Study of [F-18]RGD-K5 Positron Emission Tomography (PET) as a Tool to Monitor Response to an Anti-angiogenic Drug

Study Overview
=================
Brief Summary
-----------------
A Pilot Phase II Study The primary objective for this study is: To explore the usefulness of [F-18]RGD-K5 PET/CT to predict efficacy or early response to Avastin® (the anti-angiogenesis drug) plus chemotherapy treatment before the full course of treatment is completed The secondary objectives for this study are: To continue safety evaluation by collection of safety data from all patients To gain experience with [F-18]RGD-K5 PET/CT in order to improve the study design and conduct of future studies Design: An open label, non-randomized, uncontrolled, single group assignment, pilot efficacy study Duration: Screening visit (3-4 hrs), pre-treatment imaging visit of [F-18]RGD-K5 PET/CT (  3-4 hrs) and the standard [F-18]FDG PET/CT (  3-4 hrs) or diagnostic CT, followed by two [F-18]RGD-K5 PET/CT scans, one after the second but before the third Avastin® treatment, and one after the fourth but before the fifth Avastin® treatment, and a follow up standard [F-18]FDG PET (  3-4 hrs) or diagnostic CT. Procedures: Informed consent, collection of demographic information, medical history, blood labs, physical examination, vital signs, ECGs, three sets of [F-18]RGD-K5 dosing and imaging scans including pretreatment, early mid-treatment, and later mid-treatment, concomitant medication collection, adverse event monitoring, and assessment of tumor response to treatment Patients: Approximately forty (40) patients with non-squamous non-small cell lung cancer, metastatic breast cancer, metastatic colon or rectum cancer who will receive chemotherapy plus Avastin®. This allows for approximately 30 evaluable patients to complete this study at approximately four to eight sites internationally

Detailed Description
-----------------
The aim of this pilot study is to examine the utility of a new molecular imaging tracer, [F-18]RGD-K5 to monitor treatment responses in patients scheduled to undergo treatment with Avastin® (Bevacizumab) plus standard chemotherapy. The changes of [F-18]RGD-K5 PET/CT image scans between before treatment and after both mid-treatment cycles of Avastin® (Bevacizumab) will be evaluated. The hypothesis for this study is that changes in the uptake of [F-18]RGD-K5 PET in tumors may reflect changes in the level of integrin expression and/or angiogenesis. This pilot study will help to define if changes in uptake of [F-18]RGD-K5 are an early indicator of treatment efficacy to Avastin®.

Official Title
-----------------
A Phase II, Open Label, Non-randomized, Multi-center, Pilot, Efficacy Study of [F-18]RGD-K5 Positron Emission Tomography (PET) as a Tool to Monitor Response to an Anti-angiogenic Drug

Conditions
-----------------
Metastatic Breast Cancer, Metastatic Colon/Rectum Cancer, Non-squamous Non-small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: [F-18]RGD-K5


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient is >18 years and male or female of any race / ethnicity Patient or patient's legally acceptable representative provides written informed consent and willing to comply with protocol requirements Patient must be scheduled to receive chemotherapy treatment(s) plus Avastin® for their cancer care; treatment management will be made by the treating medical oncologists (According to the package insert for Avastin®, it is administered as an IV infusion every 3 weeks for nonsquamous non-small cell lung cancer, and every 2 weeks for metastatic breast cancer, colon or rectum cancer) Patient will be scheduled to have a clinical [F-18]FDG-PET/CT or diagnostic CT pre-treatment after the fourth but before the fifth Avastin® treatment Exclusion Criteria: Patient is not capable of complying with study procedures Female patient is pregnant or nursing; exclude the possibility of pregnancy by one of the following: Confirming in medical history that the patient is postmenopausal for a minimum of one year, or surgically sterile Confirming the patient is using one of the following methods of birth control for a minimum of one month prior to entry into this study: IUD, oral contraceptives, Depo-Provera, or Norplant Confirming a negative urine dipstick test taken the morning of receiving the [F-18]RGD-K5 Patient has a severe hepatic or renal disease as defined by previous medical history or abnormal renal and hepatic functions determined by lab results not within the following ranges, or in the opinion of the Investigator, the values are not acceptable for the patient to be included: AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limits of normal Serum creatinine ≤ 2x institutional upper limits of normal BUN within 2x institutional upper limits of normal Patient has known hyper or hypo-coagulation syndromes. (e.g. Protein C, S deficiency, Hemophilia A/B/C, Factor-V Leiden, etc) or lab results are not within the following ranges, or in the opinion of the Investigator, the values are not acceptable for the patient to be included: Platelet counts of < 75 x 103/μL Patient has known sensitivity to any components of Avastin® such as recombinant human or humanized antibodies Patient has been involved in an investigative, radioactive research procedure within 7 days and during the study participation period Patient will participate in experimental therapy procedures while participating in this clinical trial Patient has any other condition or personal circumstance that, in the judgment of the investigator, might interfere with the collection of complete data or data quality to achieve study objectives, or complete study and/or post-dose follow-up examinations

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [F-18]RDG-K5<br> | Drug: [F-18]RGD-K5<br>* Approximately forty (40) patients with non-squamous non-small cell lung cancer, metastatic breast cancer, metastatic colon or rectum cancer will receive chemotherapy plus Avastin® and will be imaged under PET/CT with [F-18]RGD-K5<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To explore the usefulness of [F-18]RGD-K5 PET/CT to predict efficacy or early response to Avastin® (the anti-angiogenesis drug) plus chemotherapy treatment before the full course of treatment is completed. |  | (5) visits over a period of approximately 5 cycles of Avastin | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To continue safety evaluation by collection of safety data from all patients. |  | (5) visits over a period of approximately 5 cycles of Avastin | 
| To gain experience with [F-18]RGD-K5 PET/CT in order to improve the study design and conduct of future studies. |  | (5) visits over a period of approximately 5 cycles of Avastin | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
[F-18]RGD-K5, RGD-K5, K5-101, Avastin, angiogenesis, anti-angiogenesis, chemotherapy, breast cancer, colon cancer, rectal cancer, lung cancer, non-squamous, non small cell