Clinical trial NCT00901264: Microculture Kinetic (MiCK) Apoptosis Test Results With Drug Treatment Results in Cancer Patients
Official title: Correlation of the Microculture Kinetic (MiCK) Apoptosis Test Results With Drug Treatment Results in Cancer Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cancer
Keywords: Chemosensitivity, chemotherapy, all cancers, personalized chemotherapy, personalized cancer treatment
Cancer Patients for whom chemotherapy is planned.
Lead sponsor: Pierian Biosciences
Sponsor class: INDUSTRY
First posted: 2009-05-13
Enrollment: 300
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cancer Patients for whom chemotherapy is planned.

Brief summary: The purpose of this study is to correlate the results of the MICK assay with short- and long-term results of treatments in cancer patients and evaluate the role of the MiCK assay in guiding chemotherapy of cancer patients.

Detailed description: Identification of those patients with cancer who will or will not respond to a specific chemotherapy is important for making decisions regarding chemotherapy regimens as well as alternative management approaches. A laboratory test that could help to determine the sensitivity of an individual patient's tumor cells to specific chemotherapeutic agents would be valuable in choosing the optimal chemotherapy regimen for that patient with an expectation of increasing the response rate to the therapy. Several types of in vitro assays that measure tumor cell survival following exposure to cytotoxic agents have been evaluated for their ability to predict chemotherapy outcomes. As a group, these assays are referred to as drug resistance assays. In a resistance assay, the surviving tumor cells can be detected directly by their exclusion or metabolism of specific dyes. Alternatively, since some of tumor cells are proliferating, their survival can be detected by measurement of DNA synthesis by radiolabeled precursor incorporation or demonstration of clonogenic potential by growth into colonies in semi-solid culture medium. In several clinical studies, these assays were useful in detecting drug resistance and in predicting a poor prognosis for cancer patients. However, these resistance assays cannot detect sensitivity of an individual patient's tumor cells to a specific drug. Therefore, new methods determining drug-sensitivity of the tumor cells of an individual patient and, thus, capable of both predicting a positive treatment outcome and guiding chemotherapy, would be of significant value.

Recently, an automated microculture kinetic (MiCK) assay for measuring drug induced apoptosis in tumor cells has been developed1-4. Apoptosis is a distinct mode of cell death which occurs under physiological conditions and yet can be induced in malignant cells by chemical and physical factors including antitumor drugs5-7. During the last decade, it has been recognized that chemotherapeutic agents exert their antitumor activity by triggering apoptosis in susceptible tumor cells8-17. This implies that the MiCK assay for apoptosis provides a mechanism-based approach to studying effects of cytotoxic agents on tumor cells. Unlike "resistance" assays that measure a fraction of cells surviving drug exposure, the MiCK assay measures a fraction of tumor cells killed by a chemotherapeutic agent via mechanism of apoptosis. Therefore the MiCK assay determines drug sensitivity, rather than resistance. Recently the MiCK assay has been shown to predict complete remission rate and survival in acute myeloid leukemia patients better than clinical criteria did18-20. In a limited study, the MiCK assay has been used to direct chemotherapy of the leukemia patients 21.

The MiCK assay has also been used to study drug-induced apoptosis in solid tumors, including neuroblastoma and colon adenocarcinoma cell lines22-23. More recent data accumulated by DiaTech has demonstrated that the MiCK assay can detect drug induced apoptosis in primary cultures of tumor cells isolated from patients with ovarian carcinoma, gastric carcinoma, metastatic breast cancer and high grade soft tissue sarcoma. The purpose of this study is to correlate the results of the MICK assay with short- and long-term results of treatments in cancer patients and evaluate the role of the MiCK assay in guiding chemotherapy of cancer patients.

Eligibility criteria: Inclusion Criteria:

* 3.1.1 Patients with pathological diagnoses of cancer or leukemia
* 3.1.2 Patients must have tumor which is accessible for biopsy and agree to undergo tumor biopsy, or drainage of malignant effusion, and the specimen must be submitted for MiCK assay.
* 3.1.3 Patients for whom chemotherapy is planned.

Exclusion Criteria:

* 3.2.1 Patients with symptomatic/uncontrolled parenchymal brain or meningeal metastasis and tumors not accessible for biopsy.
* 3.2.2 Patients who are pregnant. Pregnancy. During the course of the study, all patients of childbearing potential should be instructed to contact the treating physician if they suspect they might have conceived a child; for females, a missing or late menstrual period should be reported to the treating physician. If pregnancy is confirmed by a pregnancy test, the patient must not receive chemotherapy in this study and must not be enrolled into the study or, if already enrolled, must be withdrawn from the study. If a male patient is suspected of having fathered a child while on the study, the pregnant female partner must be notified and counseled regarding the risk to the fetus. Pregnancy during the course of this study will be reported to the Principal Investigator as a serious adverse event. Women of child bearing potential are defined to include any female who has experienced menarche and has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal (defined as amenorrhea for more than 12 consecutive months); these includes also females using oral, implanted, or injectable contraceptive hormones, mechanical devices, or barrier methods to prevent pregnancy.

Primary outcomes:
measure: To evaluate the ability of the MiCK assay to guide chemotherapy of cancer patients, with emphasis on patients failing primary treatment, patients with unknown primary tumors, and patients with tumors difficult to treat such as carcinoma of lung.
timeFrame: one year
Secondary outcomes:
measure: Correlate the MiCK assay results with objective response rates, symptom response rates, time to progression and survival of cancer patients treated with chemotherapy.
timeFrame: one year
Other outcomes:
Locations:
city: La Verne
country: United States
facility: Wilshire Oncology Medical Group, Inc
state: California
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Brentwood
country: United States
facility: DiaTech Oncology
state: Tennessee
city: Crossville
country: United States
facility: Cumberland Medical Center
state: Tennessee
city: Murfreesboro
country: United States
facility: Middle Tennessee Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Baptist Hospital
state: Tennessee
city: Nashville
country: United States
facility: Nashville Oncology Associates
state: Tennessee
city: Nashville
country: United States
facility: St. Thomas Research Institute, LLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Breast Specialists
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Toracic Surgical Specialists
state: Tennessee
city: Montreal
country: Canada
facility: DiaTech Oncology
state: Quebec
Study officials:
affiliation: Pierian Biosciences
name: Cary Presant, MD
role: STUDY_DIRECTOR
affiliation: Cumberland Medical Center
name: Dirk Davidson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nashville Oncology Associates
name: Karl Rogers, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wilshire Oncology Medical Group, Inc.
name: Swapnil P. Rajurkar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tennessee Breast Specialists
name: Laura Lawson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tennessee Thoracic Surgical Specialists
name: L. James Wudel Jr., MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Baptist Hospital Nashville
name: Raymond F Bluth, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Thomas Research Institute, LLC
name: Peter F Jelsma, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Middle Tennessee Medical Center
name: Richard D Michaelson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tampa Gerneral Hospital
name: Jorge E Marcet, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bosserman L, Rogers K, Willis C, Davidson D, Whitworth P, Karimi M, Upadhyaya G, Rutledge J, Hallquist A, Perree M, Presant CA. Application of a drug-induced apoptosis assay to identify treatment strategies in recurrent or metastatic breast cancer. PLoS One. 2015 May 29;10(5):e0122609. doi: 10.1371/journal.pone.0122609. eCollection 2015.