A Message from Marianne Balay, MS, RN Associate Director, CINJOG

A new year lies before us like an unwritten book. The pages will read about the discoveries we find in exchange for time -- and what we find along the way will largely depend on us. I'd like to take this opportunity to thank the CINJOG Network of physicians, nurses and research coordinators for your support in helping to find new discoveries to reduce the pain and suffering caused by cancer. Let us resolve to continue our fight and remember that every new day begins with new possibilities. It's up to us to fill it with things that move us toward progress.

I am very proud to start this year off with an issue of CINJOG Times featuring articles written by our CINJOG Clinical Research Associates, Ann Mondinaro and Martin Kleber. Ann Mondinaro's article speaks to one of the most important aspects of participation in clinical trials, "The reporting of serious adverse events, (SAEs)", and Martin Kleber's article addresses another very important characteristic of clinical trials, "Compliance and the proper reporting of protocol deviations and violations". Of course you will also find a listing of our open CINJOG protocols at the end of the newsletter, as well as this issue's highlighted trial for Survivors of Colorectal Cancer. Please pay special attention to this protocol since it is an important Quality of Life study that is easy to carry out in the community and the results may very well serve as an important model for other cancers. Happy New Year and happy e-reading!

Marianne Balay, MS, RN
Associate Director, CINJOG
Phone – 732-235-7150
Mobile – 908-229-9045
Email – balaymt@umdnj.edu

The Reporting of Serious Adverse Events (SAEs)
by Ann Mondinaro, BS, Clinical Research Associate, CINJOG

The purpose of this article is to underscore the proper reporting of Serious Adverse Events (SAEs) to help to protect the safety of study participants on CINJ drug trials. Timely collection and assessment of SAE reports are critical for protecting the safety of research participants. The steps below will describe the requirements and procedures for SAE reporting for CINJOG trials and may be used for other trials as specified by protocol.

STEP 1: Report the SAE to CINJ
All unexpected and/or “serious” adverse events occurring in patients while on study, or up to 30 days of being off study, will be immediately reported to the Office of Human Research Services at CINJ 732- 235-9565. As soon as you learn of the SAE, please call.

For purposes of reporting to CINJ, “serious” is defined as any adverse drug experience that results in any of the following outcomes:
1. Death
2. Life-threatening- immediate risk of death from the reaction.
3. Requires inpatient hospitalization or prolongation of existing hospitalization.
4. Results in persistent or significant disability/incapacity.
5. Results in a congenital anomaly/birth defect.
6. Requires intervention to prevent one of the outcomes listed in this definition.

The definition of serious adverse event (experience) also includes important medical events. Medical and scientific judgment will be exercised in deciding whether expedited reporting is appropriate in other situations, such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the other outcomes listed in the definition above.

STEP 2:
Complete the FDA Medwatch Report (3500A) irrespective of grade, attribution and/or expected/unexpected assessment and fax it to 732- 235-9399. Submit as much information as you have at the present time and submit a follow up form once the event resolves/evolves.

This form is located in OnCore in the study operations manual or on the FDA website.

Please note there is no longer any need to complete the "SAE Documentation Report" located in the Study Operations Manual in OnCORE. Once we receive your completed Medwatch 3500a form, we will determine if additional reporting is required to our IRB, Industrial sponsor and/or the FDA. We will handle these additional reporting requirements if they are necessary. Please report and SAEs to your local IRB as per your local IRB's policy.

NB: If the protocol requires that you complete an AdEERS report, please submit the completed AdEERS report to CINJ (as above) and there is no need to also complete/submit a Medwatch form.

STEP 3:
Complete the SAE e-CRF in OnCORE.

Compliance and the Proper Reporting of Protocol Deviations  and Violations
by Martin Kleber, BS, MA, Clinical Research Associate, CINJOG

A clinical protocol that meets scientific and ethical standards is a fundamental requirement of any clinical investigation. In order to ensure the safety and welfare of study participants and the scientific validity of the study, the approved protocol must be conducted as written. The protocol includes the detailed procedure, consent form, recruitment materials, questionnaires, and any other information relating to the research study.

In cases where deviations are unavoidable, The International Code of Harmonization (ICH) guidelines for Good Clinical Practice (GCP) offers further clarity on the responsibilities for the clinical site. It states that: The investigator should not implement any deviation from, or changes of, the protocol without agreement by the sponsor and prior review and documented approval/favorable opinion from the Internal Review Board (IRB) of an amendment, except where necessary to eliminate an immediate hazard(s) to trial subjects, or when the change(s) involves only logistical or administrative aspects of the trial (e.g., change of monitor(s), change of telephone number(s)). The investigator, or person designated by the investigator, should document and explain any deviation from the approved protocol. The investigator may implement a deviation from, or a change in, the protocol to eliminate an immediate hazard(s) to trial subjects without prior IRB approval/favorable opinion. As soon as possible, the implemented deviation or change, the reasons for it, and, if appropriate, the proposed protocol amendment(s) should be submitted (a) To the IRB for review and approval/favorable opinion; (b) To the sponsor for agreement and, if required;(c) To the regulatory authority(ies).

In no case is it permissible to intentionally deviate from the protocol by omitting required testing based on a verbal agreement with the sponsor, site logistics, budget considerations, or for patient convenience.

Breaches of protocol can be categorized as either “deviations” or “violations” 
A protocol “deviation” is as any change, divergence or departure from the study design or procedures of an IRB approved research protocol that is under the investigator’s control and has not been approved by the IRB. These are occasions when an inadvertent omission or delay in obtaining a particular study evaluation or measurement has no potential effect on a subject’s rights, safety, well being, integrity of the study data or subjects’ willingness to continue participation. All protocol deviations should be entered in the deviations tab in OnCORE. Report any deviation/violation per your IRB’s policy.

Examples of protocol deviations include but are not limited to:
•  A research subject is scheduled for follow-up visits and/or treatment outside of the protocol defined window (only if this does not adversely affect the well being of the subject of the scientific validity of the study)
•  Study schedule of events is not followed, i.e. study questionnaires are administered out of order or not administered (< 10% of the scheduled times)
•  Not obtaining an evaluation that has no possible impact on treatment decisions or the outcome of the study

A protocol “violation” is any breach from the IRB approved protocol that may affect the study subject’s rights, safety/well being, integrity of the study data, or subjects’ willingness to continue participation. These are instances where the violation harms or poses a significant or substantive risk of harm to the research subject. All protocol violations should be entered in the deviations tab in OnCORE. Report any deviation/violation per your IRB’s policy.

Examples of protocol violations include but are not limited to:
• Failure to obtain informed consent prior to initiation of study-related procedures.
• A research subject is enrolled but does not meet the protocol’s eligibility criteria.
• A research subject receives the wrong treatment.
• Treatment/dosing errors, such as dose calculation errors (> 10%), dose modifications stipulated in the protocol that were not made, etc.
• Subject met withdrawal criteria during the study but was not withdrawn and there is no written explanation
• Subject received an excluded concomitant medication

Highlighted CINJOG Study - A Quality of Life study for Survivors of Colorectal Cancer

CINJOG # 130901 - Title: Health Behaviors among Individuals Diagnosed with Colorectal Cancer

In an effort to build the groundwork for future research on health promotion among individuals with colorectal and other cancers, a team of investigators has launched a new study examining patterns in physical activity and eating habits of colorectal cancer patients who have recently finished treatment. Not counting skin cancer, colorectal cancer is the third most common cancer in both men and women, according to the American Cancer Society. The death rate from colorectal cancer has been on the decline for the past 15 years, which means more patients are surviving their disease. But are they surviving it in a way that enhances quality of life and minimizes the risk of cancer recurrence? That is one of the questions researchers at CINJ hope to answer in an effort to promote positive health behavior changes in this population.

Elliot J. Coups, PhD, behavioral scientist at CINJ and an associate professor of medicine at UMDNJ-Robert Wood Johnson Medical School, is the lead investigator of the study. Previous research by Dr. Coups shows that 80 percent of colorectal cancer survivors do not take part in regular physical activity, while 57 percent do not meet recommendations for consuming enough fruits and vegetables in their diet. Because physical inactivity and poor diet may be risk factors for colorectal cancer recurrence, Coups notes further exploration in this area is needed.  “We hope to have a better understanding of the degree to which patients modify their physical activity and dietary behaviors as a result of their diagnosis, treatment and potential emotional reactions to their illness,” said Coups. “The data collected from this study will help us determine what interventions may be successful in helping patients in this population make healthy behavior changes. It could also serve as an intervention template for other cancers.”

Study participants will fill out three surveys over a six-month period to document information such as beliefs about disease recurrence, current physical activity, and dietary intake. The influence of friends and family on the participant’s physical activity and eating habits also will be measured.  Men or women over age 21 who were diagnosed with stage I, II or III colorectal cancer and are within six weeks of having completed their cancer treatment are eligible to participate, though other criteria also must be met.

For additional information on how to participate, individuals should call 877-512-8928.

Current CINJOG Trials

Additional information on the trials listed below can be found on the CINJ web site and in the CINJOG Summer 2009 Trial Menu.

CINJOG # 030801 (NJ 1508) Modulation of Autophagy with Hydroxychloroquine in Combination with Carboplatin, Paclitaxel and Bevacizumab in Patients with Advanced/Recurrent Non-Small Cell Lung Cancer - A Phase I/II Study (page 83).

CINJOG # 040504 (NJ1105 Randomized Phase II Trial of Gemcitabine and Imatinib Mesylate versus Gemcitabine Alone in Patients with Previously Treated Locally Advanced or Metastatic Breast Cancer (page 7) .

CINJOG # 040608 (NJ 1106) Phase II Trial of Capecitabine (Xeloda) and Lapatinib (Tykerb) as First-line Therapy in Patients with HER2/neu-Overexpressing Advanced or Metastatic Pancreatic Cancer (page 6).

CINJOG # 040702 (NJ 2107) A Phase II Trial of Doxil, Carboplatin and Bevacizumab in Triple Negative Previously Untreated Metastatic Breast Cancer (page 5).

CINJOG # 040706 (NJ 1107) A Phase I/II Trial of Letrozole (Femara) and Sorafenib (Nexavar) in Postmenopausal Women with Hormone-Receptor Positive Locally Advanced or Metastatic Breast Cancer (page 12).

CINJOG # 040803 Phase I/II Study of Weekly Abraxane and RAD001 in Women with Locally Advanced or Metastatic Breast Cancer (page 9)

CINJOG # 040804 (NJ 1108) A Phase I/II Study of Ixabepilone in Combination with the Autophagy Modulator Hydroxychloroquine for the Treatment of Patients with Metastatic Breast Cancer (page 11).

CINJOG # 070806 Autophagy and Anti-Angiogenesis in Metastatic Colorectal Carcinoma: A Phase II trial of Hydroxychloroquine to Augment Effectiveness of XELOX-Bevacizumab(page 42) .

CINJOG # 080804 A Phase II, Multicenter Trial of Genciabine, Carboplatin, and Sorafenib in Chemotherapy-naïve Patients with Advanced/Metastatic Bladder Carcinoma (page 54) .

CINJOG # 080805 (NJ2080) A Phase II Study of Docetaxel and Modulation of Autophagy with Hydroxychloroquine for Metastatic Hormone Refractory Prostate Cancer (page 53).

CINJOG # 080811 A Phase II trial of Atorvastatin and Celecoxib in Patients with Hormone-Dependent Prostate-Specific Antigen Progression after Local Therapy for Prostate Cancer (page 52).

CINJOG # 080803 (NJ1808) Autophagic Cell Death in Patients with Hormone-dependent Prostate-Specific Antigen Progression after Local Therapy for Prostate Cancer (page 51) .