Attach_3_SOW2015_Dec20 2015.pdf

December 20, 2015

Statement of Work “Preclinical Pharmacokinetic and Pharmacology Evaluations of

Agents Being Developed for Cancer Patients.”

A. Independently and not as an agent of the Government, the Contractor shall furnish all of the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government, as required to perform the work stated below in accordance with protocols to be developed by the National Cancer Institute’s (NCI) Contracting Officer Representative (COR).

Compounds under evaluation will vary in their stage of development and in their requirements for evaluation. Therefore, Task Orders specific for each compound will be developed by the COR and the Contractor shall perform one or more of the following:

1. Implement and validate COR-designated analytical methods that are sufficiently sensitive, specific, and reproducible for measurement and quantitation of assigned test agents (e.g., small molecule therapeutics and well-characterized biologicals) and metabolites in body fluids and/or tissues of animals and humans at therapeutic and/or toxic concentrations.

2. Conduct pharmacokinetic evaluations in animals (e.g., mice, rats, tumor-bearing rodents, optionally larger animals) to support early lead and candidate drug characterization. Various routes of administration (e.g., intravenous, oral, intraperitoneal, subcutaneous, continuous infusion, etc.)

may be utilized. Evaluations may include collection of multiple blood samples to obtain plasma or serum and, in some evaluations, collection of urine, feces, tissues or tumor samples. Detailed protocols will be provided by the COR.

3. Utilize established analytical methods/protocols to determine concentrations of test agents in various matrices (cell extracts, media, plasma, urine, bile, saliva, tumors, and normal tissues) that may be derived from:

(a) Pharmacokinetic evaluations conducted under item 2 above;

(b) Other Government-sponsored laboratories

(c) Human clinical trials

4. Use state-of-the-art modeling software to fit concentration vs. time data

(for plasma and possibly tissues) to suitable non-compartmental and/or compartmental pharmacokinetic models and calculate relevant pharmacokinetic parameters (e.g., half-life, volume of distribution, area under the curve, clearance, etc.) for a given agent and route of administration.

5. Calculate systemic bioavailability for various routes (e.g., oral, ip, sc) and determine if bioavailability is dose-dependent. Calculate mass-balance parameters when sufficient data are collected.

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December 20, 2015

6. Determine the suitability of standard formulation strategies for the administration of test agents to animals by the desired route and at the desired dose level(s).

7. Determine the in vitro plasma protein binding and stability of test agents in biological fluids and tissues using standard techniques.

8. Carry out Pharmacokinetic-Pharmacodynamic (PK-PD) evaluation protocols (developed by the COR) in tumor-bearing mice and collect plasma, tissue, and/or tumor samples for drug level determinations and analysis of specified pharmacodynamic endpoints.

9. Utilize standard mass spectroscopic techniques to characterize the metabolites and/or degradation products of test agents present in blood, plasma, urine, and/or other fluids. The extent of metabolite characterization will be specified by the NCI COR.

10. Store samples generated in-house or received from other laboratories under suitable conditions and ship samples to other laboratories upon request by the NCI COR.

B. SAMPLE TASK ORDERS

Sample Task Order Requests to be included in the solicitation are specified below:

1. Pharmacokinetic and Bioavailability Evaluations of Anticancer Compounds in Mice.

2. Pharmacokinetic-Pharmacodynamic-Efficacy Evaluations of Anticancer Compounds in Tumor-Bearing Mice.

3. Analytical Support for Pharmacology Evaluations with Selected Anticancer Agents

4. Determination of [NSC – to be determined] in Plasma and Urine Samples from an NCI-supported Human Phase I Clinical Trial.

5. Kick-off Meeting with NCI Staff