E-Newsletter - March 2024
Spotlight on Alliance Trials

Six Alliance clinical trials focusing on treatment and one on symptom intervention of patients with colorectal cancer and bladder cancer take the spotlight in this issue:

  • A022004 (Stage II/III BRAF V600E colon cancer)
  • A022101 (Limited metastatic colorectal cancer)
  • A221805 (Chemotherapy-induced peripheral neuropathy)
  • A031701 (Invasive bladder cancer)
  • A031803 (Non-muscular invasive bladder cancer)
  • A032002 (Metastatic bladder cancer)
  • A032103 (Muscle invasive bladder cancer)

Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in the United States. CRC strikes men and women with almost equal frequency, while someone with a family history of colorectal cancer has a 10 to 15 percent chance of developing the disease. The following are active CRC trials now enrolling participants.

A022004 (Stage II/III BRAF V600E colon cancer)
Researchers want to find a more effective treatment to reduce the chance of cancer recurrence in patients with BRAF-mutated stage IIB-III colon cancer. A clinical trial led by Rona Yaeger, MD, of Memorial Sloan Kettering Cancer Center, seeks to compare treatment with encorafenib and cetuximab to usual care (patient observation) for reducing the chance of cancer recurrence after standard surgery and chemotherapy in patients with BRAF-mutated stage IIB-III colon cancer.

Encorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of tumor cells. This may help keep tumor cells from growing. Giving encorafenib and cetuximab after standard surgery and chemotherapy may be more effective at reducing the chance of cancer recurrence compared to the usual patient observation.

Official title: Randomized trial of consolidation targeted adjuvant therapy with encorafenib and cetuximab versus usual care for patients with stage II/III BRAF V600E colon cancer
Learn more: https://bit.ly/Alliance-A022004


A022101 (Limited metastatic colorectal cancer)
This clinical trial led by Eric Miller, MD, PhD, of Ohio State University Comprehensive Cancer Center, compares total ablative therapy and usual systemic therapy to usual systemic therapy alone in treating patients with colorectal cancer that has spread to up to four body sites (limited metastatic). The usual approach for patients who are not participating in a study is treatment with intravenous (IV) (through a vein) and/or oral medications (systemic therapy) to help stop the cancer sites from getting larger and the spread of the cancer to additional body sites.

Ablative means that the intention of the local treatment is to eliminate the cancer at that metastatic site. The ablative local therapy will consist of very focused, intensive radiotherapy called stereotactic ablative radiotherapy (SABR) with or without surgical resection and/or microwave ablation, which is a procedure where a needle is temporarily inserted in the tumor and heat is used to destroy the cancer cells. SABR, surgical resection, and microwave ablation have been tested for safety, but it is not scientifically proven that the addition of these treatments are beneficial for your stage of cancer. The addition of ablative local therapy to all known metastatic sites to the usual approach of systemic therapy could shrink or remove the tumor(s) or prevent the tumor(s) from returning.

Official title: A pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur)
Learn more: https://bit.ly/Alliance-A022101


A221805 (Chemotherapy-induced peripheral neuropathy)
Ellen M. Lavoie Smith, PhD, RN, FAAN, of the University of Alabama School of Nursing, leads a clinical trial that seeks the best dose of duloxetine and how well it works in preventing pain, tingling, and numbness (peripheral neuropathy) caused by treatment with oxaliplatin in patients with stage II-III colorectal cancer. Duloxetine increases the amount of certain chemicals in the brain that help relieve depression and pain. Giving duloxetine in patients undergoing treatment with oxaliplatin for colorectal cancer may help prevent peripheral neuropathy.

Official title: Duloxetine to prevent oxaliplatin-Induced chemotherapy-induced peripheral neuropathy: A randomized, double-blind, placebo-controlled phase II to phase III study
Learn more: https://bit.ly/AllianceA221805


Considered a relatively rare form of cancer, bladder cancer starts in the lining of the bladder. The most common type of bladder cancer is urothelial carcinoma, which starts in the urothelial cells that line the inside of the bladder. Bladder cancers that have spread into the wall of the bladder are classified as non-invasive (inner layer of cells) and invasive (deeper layers of the bladder wall). Bladder cancer that has not grown into the muscle layer is described non-muscle invasive bladder cancer (NMIBC). The following are active bladder cancer trials now enrolling participants.

A031701 (Invasive bladder cancer)
The standard therapy for bladder cancer that invades the muscle wall (“muscle-invasive bladder cancer”) is chemotherapy followed by surgery to remove the bladder. The purpose of this study that Gopakumar Iyer, MD, of Memorial Sloan Kettering Cancer Center, leads is to see if some patients with muscle-invasive bladder cancer can avoid surgery to remove their bladder. This clinical trial studies how well gemcitabine hydrochloride and cisplatin work in treating participants with invasive bladder urothelial cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Official title: A phase II study of gemcitabine plus cisplatin chemotherapy in patients with muscle-invasive bladder cancer with bladder preservation for those patients whose tumors harbor deleterious DNA damage response (DDR) gene alterations
Learn more: https://bit.ly/AllianceA031701


A031803 (Non-muscle invasive bladder cancer)
Michael Woods, MD, of Loyola University Medical Center, leads this clinical trial that studies how well gemcitabine together with pembrolizumab works in treating patients with non-muscle invasive bladder cancer (NMIBC) who are unresponsive to the bacillus Calmette-Guérin (BCG) vaccine. NMIBC accounts for about 70 percent of all bladder cancer and is associated with a more than 88 percent survival rate over five years. Despite significant advances in the management of NMIBC, it remains associated with significant morbidity and mortality due to its tendency to recur and progress to muscle-invasive or systemic disease. This trial may have a significant impact on future research.

The results of this trial may provide a novel treatment approach to this patient population and support the importance of additional research combining intravesical therapy (injecting drug directly into the bladder) with immune checkpoint inhibition. Conversely, the results may direct urologic research toward different combinations of therapies for BCG-unresponsive non-muscle invasive bladder cancer.

Official title: Phase II trial of intravesical gemcitabine and MK-3475 (pembrolizumab) in the treatment of patients with BCG-unresponsive non-muscle invasive bladder cancer
Learn more: https://bit.ly/AllianceA031803


A032002 (Metastatic urothelial cancer)
This clinical trial led by Himanshu Nagar, MD, of Weill Cornell Medicine, compares the effect of adding radiation therapy to an immunotherapy drug called atezolizumab versus atezolizumab alone in treating patients with urothelial cancer that has spread to other places in the body (metastatic). The addition of radiation to immunotherapy may shrink the cancer, but it could also cause side effects. Immunotherapy with monoclonal antibodies such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy (SBRT) is a type of radiation therapy that uses high energy x-rays to kill tumor cells and shrink tumors. This method uses special equipment to position a patient and precisely deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and may cause less damage to normal tissue than conventional radiation therapy. The combination of atezolizumab and radiation therapy may be more efficient in killing tumor cells.

Official title: Phase II randomized trial of atezolizumab versus atezolizumab and radiation therapy for platinum ineligible/refractory metastatic urothelial cancer (ART)
Learn more: https://bit.ly/Alliance-A032002


A032103 (Muscle invasive bladder cancer)
Eric Miller, MD, PhD, of Ohio State University Comprehensive Cancer Center, leads this clinical trial that examines whether patients who have undergone surgical removal of bladder, but require an additional treatment called immunotherapy to help prevent their bladder cancer from coming back, can be identified by a blood test. Many types of tumors tend to lose cells or release different types of cellular products including their DNA which is referred to as circulating tumor DNA (ctDNA) into the bloodstream before changes can be seen on scans. Health care providers can measure the level of ctDNA in blood or other bodily fluids to determine which patients are at higher risk for disease progression or relapse. In this study, a blood test is used to measure ctDNA and see if there is still cancer somewhere in the body after surgery and if giving a treatment will help eliminate the cancer.

Immunotherapy with monoclonal antibodies, such as nivolumab and relatlimab, can help the body's immune system to attack the cancer, and can interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine if ctDNA measurement in blood can better identify patients that need additional treatment, if treatment with nivolumab prolongs patients' life and whether the additional immunotherapy treatment with relatlimab extends time without disease progression or prolongs life of bladder cancer patients who have undergone surgical removal of their bladder.

Official title: MODERN: An integrated phase 2/3 and phase 3 trial of MRD-based optimization of ADjuvant ThErapy in URothelial CaNcer
Learn more: https://bit.ly/Alliance-A032103


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