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MEDIOLA: A Clinical Trial Combining a PARP Inhibitor with an Immunotherapy Drug

January 31, 2017

By Ding Wang, MD and Catherine Jenovai

immune system cells attacking cancer cellImmune system and cancer

Every day our bodies are exposed to various injuries that may damage our cells. The damaged cells with certain types of genetic defects are tagged as abnormal and removed by our immune system. If something goes wrong and the cells are not removed by our immune system, they may become cancer cells over time. Sometimes cancer cells figure out a way to hide from our immune system by producing a molecule called PDL-1 (programmed death ligand-1), which uses camouflage to trick the immune system into thinking they are healthy cells.

Immunotherapy for cancer treatment

Anticancer drugs called immunotherapy have been developed to combat this trick. One type of immunotherapy, called Anti-PDL-1 antibodies, binds to the PDL-1 molecule on cancer cells. This allows the patient’s immune system to find, unmask, and destroy cancer cells. The drug MEDI4736 is an Anti-PDL-1 antibody that is being tested in research in combination with other drugs to treat certain cancers.

DNA damage repair, PARP inhibitors, and cancer

PARP inhibitors are drugs that specifically target cancer cells with mutations in some of the genes involved in repairing damaged DNA. In people with BRCA mutations, the BRCA repair pathways do not function properly and are unable to repair certain types of DNA damage. This can lead to cancer developing. By treating with a PARP inhibitor, such as olaparib, both DNA repair pathways will be shut off in the cancer cells, which makes the cancer cells more likely to respond to treatment.

MEDIOLA

Mediola logoMediola is an important clinical trial. It’s a Phase I/II study combining both of these mechanisms to target cancer cells. First patients received the PARP inhibitor Olaparib for 4 weeks, then they will receive both Olaparib and an immunotherapy drug called MEDI4736 (known as an “Anti-PDL-1” drug) that helps the immune system attack cancer cells. All patients enrolled in this study will be given the study medications, a combination of both MEDI4736 and olaparib, after the initial four-week period of taking olaparib alone.

Patients with a BRCA mutation who are diagnosed with platinum-sensitive relapsed ovarian cancer or HER2-negative metastatic breast cancer are eligible. Patients with relapsed small cell lung cancer or gastric cancer (including gastroesophageal junction adenocarcinoma) would be eligible to participate even if they don’t carry a BRCA mutation. Patients who participated on PARP inhibitor trials, but were randomized to receive placebo or physician’s choice therapy, are allowed to participate in MEDIOLA.

Learn more about MEDIOLA

For more information about MEDIOLA, call 877-400-4656 or visit cancerstudylocator.com/azo/trial/113408/.

Dr. Ding Wang is the Medical Director of the Clinical Trials Office at the Henry Ford Cancer Institute at Henry Ford Hospital in Detroit, MI.  Dr. Wang works with all treating physicians and meets with all Phase 1 patients, ensuring that they and their families understand and play an important role in the care plan by sitting down with them to review radiology images and progress.  Building relationships through a solid foundation of trust is critical to Dr. Wang, and nearly 100 percent of his patients give him the highest satisfaction rating via Press Ganey surveys.  Dr. Wang is a tumor board member for CNS, GYN, Thyroid, Melanoma, and is on the Precision Medicine Task Force at Henry Ford Hospital.  He is dedicated to the growth of clinical trials operations, and  is committed to offering more novel therapeutic alternatives for patients who cannot receive standard of care therapies. 

Catherine Jenovai is a manager in the clinical trials office at Henry Ford Hospital. She is the lead coordinator of the Phase I program working under Dr. Wang.

 

 

 

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2 Comments

  1. David Mutch says:

    How many priors??

    • Sue Friedman says:

      Here is the response from the study coordinator:

      The prior lines are cohort specific:

      Ovarian
      ·Received at least 1 previous course of platinum-based therapy and must be considered to be platinum sensitive (relapsed at least 24 weeks after the administration of their last platinum treatment).

      Breast
      · Must have previously received treatment with an anthracycline (eg, doxorubicin, epirubicin) unless contraindicated and/or a taxane (eg, paclitaxel, docetaxel) in either a neo-adjuvant/adjuvant or metastatic setting.
      · Patients who have received prior platinum-based chemotherapy are eligible if platinum was given either as potentially curative treatment for a prior non-breast cancer (eg, ovarian cancer) with no evidence of disease for ≥5 years prior to study entry or as adjuvant/neo-adjuvant treatment for breast cancer provided at least 12 months have elapsed between the last dose of platinum-based treatment and randomization.
      · Patients who have received platinum therapy for advanced breast cancer are eligible to enter the study provided there has been no evidence of disease progression during the platinum chemotherapy.
      · Patients cannot have received more than 2 prior lines of cytotoxic chemotherapy for metastatic disease.

      Gastric
      · Metastatic or recurrent gastric adenocarcinoma (including gastroesophageal junction adenocarcinoma) that has progressed following first-line therapy, confirmed by imaging modalities:
      o The first-line regimen must have contained at least a doublet 5-fluoropyrimidine and platinum based regimen.
      o Capecitabine is an acceptable 5-fluoropyrimidine-containing agent.
      o Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy containing doublet 5-fluoropyrimidine and platinum based regimen is considered as first-line therapy.
      o Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the first-line therapy. For HER2-negative patients: More than 1 prior chemotherapy regimen (except for adjuvant/neoadjuvant chemotherapy with more than 6 months wash-out period) for the treatment of gastric cancer in the metastatic or recurrent setting.
      o For HER2-positive patients: More than 2 prior chemotherapy regimens (except for adjuvant/neoadjuvant with more than 6 months wash-out period) for the treatment of gastric cancer in the metastatic or recurrent setting.

      Lung
      · Relapsed SCLC patients may have limited or extensive stage disease, and the disease should have relapsed >12 weeks following first-line platinum-based therapy. Should patients have received a second course of platinum-based therapy, then the same criterion (ie, the patient should have relapsed >12 weeks following the second course) applies.

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