There is a new direction of cancer treatments being explored. This area of research focuses on helping the body’s natural “repairmen” (a.k.a PARP inhibitors) instead of the mutated cancer cells themselves. These trails are particularly exciting for breast cancer (and other types of non-breast cancer) patients who have been diagnosed with a sub-category of cancer that does not respond to current treatments. Below is the result of LIFE Family of publications dedication to this subject matter. Our research represents months of work, and a gift to you our readers and anyone you know and love touched by this cancer and any other. Please share this October magazine via sending the link to it to anyone you care about: www.lifepubs.com/breastcancer.

AG014699: A PARP inhibitor, developed by Pfizer, and tested by Cancer Research UK. Phase 1 trials ended in 2005 and involved combining AG014966 with the treatment drug temozolomide. Trials focused on patients with advanced tumors. The drug combination had a 10% response rate and is being studied further. Dr. Smith is currently at Morris Brown College researching AG014699 in patients with BRCA1 or BRCA2 gene mutations with metastatic breast cancer or ovarian cancer. Questions for Smith should be sent to the Morris Brown College office at 404-220-0140 or 404-888-0681.

CEP-9722: A PARP inhibitor being tested by Cephalon (test ID NCT00920595). CEP-9722 is being tested both as single-agent therapy (no additional cancer treatments) and as combination therapy (combining CEP-9722 with temozolomide). The trial is currently seeking patients with advanced solid tumors. TNBC patients are great candidates (even if no BRCA gene mutation is present)—especially if other cancer treatments have been unresponsive. For trial participation information, call 1.877.237.4879.

Iniparib (BSI-201): A PARP inhibitor treatment currently in phase two and phase three (with over 400 patients in trials) at BiPar Sciences. The drug is being used to treat breast cancer, ovarian cancer, uterine cancer, and brain tumors.

The FDA has “fast-tracked” the drug in hopes of widespread use to TNBC patients by granting Iniparib the Extended Access Protocol (AP) approval. This means women in the US with no comparable/satisfactory treatment options for TNBC (and who do not qualify for appropriate clinical trials) have the opportunity to access Iniparib through EAP. Contact the BiPar Sciences hotline at 1.866.668.2232 for more information.

Olaparib (AZD2281/ KU-0059436): A PARP inhibitor treatment drug currently in numerous trials (performed by pharmaceutical company AstraZeneca). There are two open trials listed below, but contact AstraZeneca to find out about constantly updated trial statuses and new Olaparib trials.

1. Trial partnering AstraZeneca with Aptium Oncology Gastrointestinal Cancer Consortium (trial ID CT00912743). This drug could (if approved by FDA) be a treatment option for cancers in people with hereditary BRCA1 or BRCA2 mutations (ovarian cancer, breast cancer—including eligible TNBC patients—and prostate cancers). Phase one trials had 19 patients with BCRA-mutated tumors that were not responding to other treatments. After the trial, 12 of the patients’ tumors shrank or stabilized. Phase two trials are currently underway with breast cancer (including eligible TNBC patients), ovarian cancer and colorectal cancer patients. Contact for trial participation is the AstraZeneca Cancer Study Locator Service (877.400.4656, astrazeneca@emergingmed.com).

2. Trial partnering AstraZeneca with KuDOS Pharmaceuticals Limited (trial ID NCT00516724). The study is testing the drug Olaparib (KU-0059436) in combination with Carboplatin and/or Paclitaxel chemotherapy. Contact for trial participation is the AstraZeneca Clinical Information Center (1.800.236.9933, information.center@astrazeneca.com).

Oltipraz (NFE2L2—also known as Nrf2): A bardoxolone AIM that reduces/regulates oxidative stress. Oxidative stress can result in cancer (as well as cardiovascular diseases, inflammation, neurological diseases, and renal disease). In rodent trials, Oltipraz was shown to inhibit cancer formation. However, trials have shown significant side-effects, such as numbness, tingling, pain in the extremities, and gastrointestinal toxicity. Oltipraz is still being tested as a chemopreventative. So, if a patient has not been response to chemotherapy, Oltipraz may be an alternative. Trials are not specific to breast cancer, but do include breast cancer participants. The bardoxolone AIM drug INO-001 (sometimes incorrectly referred to as a PARP enzyme) is specific to breast cancer research. No current trials are listed, but the following institutions have been known to study different bardoxolone AIMs and their effects on all types of cancer:

1. Rutgers New Brunswick – Department of Pharmaceutics: Dr. Tony Ah-Ng Kong (732.445.3831 ext. 228/226, KongT@rci.rutgers.edu)

2. Albert Einstein College of Medicine: Dr. Wenge Li (Room 455, 718.678.1016, wenge.li@einstein.yu.edu)

3. University of Dundee: Dr. M. McMahon (m.j.m.mcmahon@dundee.ac.uk)

4. The Ohio State University Medical Center: Dr. Jay Zweier (614.247.7788) and Dr Frederick Aman Villamena(614-292-8215, villamena.1@osu.edu)

MK4827: A PARP inhibitor treatment drug developed (and being tested) by Merck. The drug is in phase one (trial ID NCT00749502) and is being tested on patients with solid tumors, ovarian neoplasms or prostate cancer. Studies hope to find MK4827 causes at least 50% inhibition of the PARP enzyme activity (how the body repairs mutated cells). The study findings will reflect how MK4827 acts in the body alone (no combination of the PARP inhibitor with other treatments). Therefore, it should be noted that this study excludes patients who had chemotherapy, radiotherapy, hormonal therapy or biological therapy within four weeks prior to the trial. For trial participation information, call 1.888.577.8839.

Veliparib (ABT-888): A PARP inhibitor treatment drug (developed by Abbott) currently in numerous trials. This drug could (if approved by FDA) be a treatment option for numerous types of cancers—including TNBC patients.

1. At the Cancer Institute of New Jersey, ABT-888 is being tested on patients’ metastatic cancer, solid tumors, or non-Hodgkin lymphoma. During this trial, they are combining ABT-888 with traditional chemotherapy (cyclophosphamide and doxorubicin), specifically testing if they can remove the chemotherapy drug doxorubicin. Phase one/two of trials started in 2008 and are expected to be complete by 2010. Principal Investigator is Antoinette R. Tan, MD. She can be contacted at tanan@umdnj.edu.

2. At Massachusetts General Hospital, ABT-888 is being tested on patients with metastatic breast cancer and BRCA1/2 breast cancer. During this trial, they are combining ABT-888 with the drug temozolomide. It is hoped that adding ABT-888 will help cells rebuild after chemotherapy by preventing just the cancer cells from re-building. The trials are in phase 2 and are recruiting. The hospital joined forces with a research “super team” in 2010 (compiled of 5 research teams also testing cancer drugs) called I-SPY2 (or Investigation of Serial Studies to Predict your Therapeutic Response with Imaging and Molecular Analysis) in an effort to fast track FDA approval. As a result, any new participants in the ABT-888 trial would also be taking 4 other drugs: AMG 655 (Conatumumab), Amgen’s AMG 386, CP-751,871 (Figitumumab) and HKI-272 (Neratinib). Principle Investigator is Steven Isakoff, MD; PhD. Contact for trial participation is Karleen Habin (617.726.1922, khabin@partners.org).