Predicting Responsiveness in Oncology Patients Based on Host Response Evaluation During Anti Cancer Treatments

Overview

About this study

The objectives of this study are to create a proteomic profile (Host Response) using plasma from patients before and after anti-cancer therapy, and to associate the changes in the levels of plasma proteins with response to treatment (ORR) as defined by RECIST 1.1 /other validated clinical scale to assess response.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

Provision of informed consent prior to any study-specific procedures.
Male or female aged at least 18 years.
ECOG PS – 0/1-2.
Normal hematologic, renal and liver function:
- Absolute neutrophil count > 1500/mm^3;
- Platelets > 100,000/mm^3;
- Hemoglobin > 9 g/dL;
- Creatinine concentration ≤ 1.4 mg/dL, or creatinine clearance > 40 mL/min;
- Total bilirubin < 1.5 mg/dL, ALT+ AST levels ≤ 3 times above the upper normal limit.
The patient must have at least one measurable lesion and the relevant images in order to enable the assessment of the response.

Exclusion Criteria:

Any concurrent and/or other active malignancy that has required systemic treatment within 2 years of first dose of treatment.
Generalized impairment or mental incompetence that would render the patient unable to understand his/her participation in the study.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location	Status	Contact
Jacksonville, Fla. Mayo Clinic principal investigator Yanyan Lou, M.D., Ph.D.	Closed-enrolling by invitation What is this? (?) "Close" Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.	Contact information: Cancer Center Clinical Trials Referral Office 855-776-0015

Mayo Clinic Location

Status

Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Yanyan Lou, M.D., Ph.D.

Closed-enrolling by invitation

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Local and systemic treatments for cancer include surgery, radiation, chemotherapy, hormonal therapy, molecularly targeted therapies, antiangiogenic therapy, and immunotherapy. Many of these therapies can be curative in patients with early stage disease, but much less frequently is this the case when they are used to treat advanced-stage metastatic disease. In the latter setting, innate and/or acquired resistance are among the reasons for reduced responsiveness or nonresponsiveness to therapy, or for tumour relapse after an initial response. Most studies of resistance or reduced responsiveness focus on 'driver' genetic (or epigenetic) changes in the tumour-cell population. Several studies have highlighted the contribution of therapy-induced physiological changes in host tissues and cells that can reduce or even nullify the desired antitumour effects of therapy. These unwanted host effects can promote tumour-cell proliferation (repopulation) and even malignant aggressiveness. These effects occur as a result of systemic release of numerous cytokines, and mobilization of various host accessory cells, which can invade the treated tumour microenvironment. In short, the desired tumour-targeting effects of therapy (the 'yin') can be offset by a reactive host response (the 'yang'); proactively preventing or actively suppressing the latter represents a possible new approach to improving the efficacy of both local and systemic cancer therapies. Read More on PubMed
Rapid or accelerated tumor cell repopulation after significant tumor cell killing induced by various cytotoxic agents often compromises the expected therapeutic benefit of such tumor responses. Here, we discuss the concept that tumor cell repopulation after certain cytotoxic therapies, using vascular disrupting agents as an example, may be aided by a reactive, systemic host response involving the mobilization of bone marrow-derived circulating cells, including endothelial progenitor cells, which subsequently home to the vasculature of treated tumors and promote tumor neovascularization. These vasculogenic "rebounds" can be blocked, at least in some cases, by treatment with an antiangiogenic drug. There is limited preliminary evidence that maximum tolerated dose chemotherapy causes a similar effect. This could constitute one way by which antiangiogenic therapy could increase the efficacy of conventional cytotoxic chemotherapy regimens; it also raises the specter of new molecular targets for systemic cancer therapies which are involved in therapy-induced bone marrow-derived cell mobilization, homing to tumors, and tumor retention. Read More on PubMed
Perhaps the most significant recent advance in oncology therapeutics has been the approval of various "molecularly targeted" anti-cancer drugs. Currently, there are a large number of similar drugs in early or late stage development, including antiangiogenic agents. Clinical development of such drugs suffers from several handicaps including determining whether a patient's cancer expresses the target and is functionally contributing to cancer growth, monitoring biologic activity, and determining optimal biologic dose. The last problem is related to the low frequency of objective tumor responses (tumor shrinkage) caused by such drugs, or the lack of dose limiting toxicities necessary to define a maximum tolerated dose (MTD), or expression of optimal therapeutic activity at doses below the MTD, when one can be defined. These problems necessitate the development of alternative pharmacodynamic surrogate markers. Here we summarize several such promising markers for monitoring targeted antiangiogenic activity, and establishing optimal therapeutic/biologic dosing. The first is molecular--plasma VEGF--levels of which are rapidly and significantly increased in a dose dependent manner after injection of normal or tumor bearing mice with anti-VEGFR-2 antibodies. The second is a cellular marker, and more generic in nature--circulating VEGF receptor-2 positive cells found in peripheral blood, some of which may be circulating endothelial progenitor cells. Levels of such cells are suppressed in a dose dependent manner which correlate with previously determined optimal biologic/therapeutic anti-tumor activity of various antiangiogenic drugs or treatments. Finally, another promising marker we discuss is soluble VEGFR-2. Read More on PubMed

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