E-Newsletter - December 2023
Spotlight on Alliance Trials

 

alLIANCE Activates 13 New Trials This Year

The year 2023 has been a robust year for trial activation by the Alliance for Clinical Trials in Oncology. This year, Alliance opened 13 trials across various disease sites and modalities, including but not limited to triple-negative breast cancer, colon cancer, sarcomatoid mesothelioma, and B-cell acute lymphoblastic leukemia. Take a look at these new trials.

Advanced Pancreatic Cancer

Alliance A022106: Phase II/III second-line NABPLAGEM vs. nab-paclitaxel/gemcitabine in BRCA1/2 or PALB2 mutant metastatic pancreatic ductal adenocarcinoma (PLATINUM)
Overview: This phase II/III trial compares the effect of the combination of nab-paclitaxel plus cisplatin and gemcitabine versus (vs.) nab-paclitaxel plus gemcitabine for the treatment of pancreatic cancer that has spread from where it first started (primary site) to other places in the body (metastatic) with genetic mutations in the BRCA1 or BRCA2 or PALB2 genes. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill tumor cells. Giving nab-paclitaxel in combination with cisplatin and gemcitabine may work better than nab-paclitaxel plus gemcitabine for the treatment of metastatic pancreatic cancer.

Study Chair: Andrew H. Ko, MD, UCSF Helen Diller Family Comprehensive Cancer Center
Activated: 12/1/2023 | CT.gov Link: https://bit.ly/Alliance-A022106

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ComboMATCH | RAS-Mutant Cancers

Alliance EAY191-A3: Palbociclib and Binimetinib in RAS-Mutant Cancers
Overview: This phase II clinical trial evaluates the effectiveness of palbociclib and binimetinib in treating patients with RAS-mutated cancers. Palbociclib and binimetinib are both in a class of medications called kinase inhibitors. They work by blocking the action of abnormal proteins that signals cancer cells to multiply. This trial may help researchers understand if giving the combination of palbociclib and binimetinib can help improve the amount of time before the cancer grows in patients with patients with low grade serous ovarian cancer who have certain changes in the tumor DNA. This trial may also help researchers understand if giving the combination of palbociclib and binimetinib can help improve outcomes among patients with low grade serous ovarian cancer who have previously received a MEK inhibitor. For patients with other tumors, with the exception of lung cancer, colon cancer, melanoma and low grade serous ovarian cancers, this trial may help researchers understand if giving the combination of palbociclib and binimetinib can improve the clinical outcome of survival without progression in patients who have certain changes in their tumor's DNA.

Study Chair: Geoffrey I Shapiro, MD, PhD, Dana-Farber Cancer Institute
Activated: 11/15/2023 | CT.gov Link: https://bit.ly/cmatch-A3

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Advanced Nasopharyngeal Cancer

Alliance A092105: Randomized phase 2 study of nivolumab and ipilimumab with or without cabozantinib in patients with advanced nasopharyngeal carcinoma that have progressed after platinum treatment and immunotherapy
Overview: This phase II trial tests how well nivolumab and ipilimumab immunotherapy with or without cabozantinib works in treating patients with nasopharyngeal cancer that has come back (after a period of improvement) (recurrent), has spread from where it first started (primary site) to other places in the body (metastatic), or for which no treatment is currently available (incurable). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving immunotherapy with nivolumab and ipilimumab and targeted therapy with cabozantinib may help shrink and stabilize nasopharyngeal cancer.

Study Chair: Glenn J. Hanna, MD, Dana-Farber Cancer Institute
Activated: 09/18/2023 | CT.gov Link: https://bit.ly/Alliance-A092105

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Mantle Cell Lymphoma

Alliance A052101: A randomized phase 3 trial of continuous vs. intermittent maintenance therapy with zanubrutinib as upfront treatment in older patients with mantle cell lymphoma
Overview: This phase III trial tests whether continuous or intermittent zanubrutinib after achieving a complete remission (CR) with rituximab works in older adult patients with mantle cell lymphoma (MCL) who have not received treatment in the past (previously untreated). Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Zanubrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. When zanubrutinib is used in MCL, the current standard of care is to continue administering the drug indefinitely until disease progression. This continuous treatment comes with clinical as well as financial toxicity, which could be especially detrimental in older patients. For patients who achieve a CR after initial zanubrutinib plus rituximab therapy, it may be safe and equally effective to stop treatment and restart zanubrutinib upon disease progression rather than continuing indefinitely in previously untreated older adult patients with MCL.

Study Chair: Anne Beaven, MD, University of North Carolina Chapel Hill
Activated: 09/8/2023 | CT.gov Link: https://bit.ly/Alliance-A052101

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ComboMATCH | Advanced Biliary Tract Cancers

Alliance EAY191-A6: A ComboMATCH Treatment Trial: FOLFOX in combination with binimetinib as 2nd line therapy for patients with advanced biliary tract cancers with MAPK pathway alterations
Overview: This phase II ComboMATCH treatment trial that compares the usual treatment of modified leucovorin, fluorouracil and oxaliplatin (mFOLFOX6) chemotherapy to using binimetinib plus mFOLFOX6 chemotherapy to shrink tumors in patients with biliary tract cancers that have spread to other places in the body (advanced) and had progression of cancer after previous treatments (2nd line setting). Fluorouracil is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It works by killing tumor cells. Leucovorin may help the other drugs in the mFOLFOX6 chemotherapy regimen work better by making tumor cells more sensitive to the drugs. Binimetinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals tumor cells to multiply. This helps to stop or slow the spread of tumor cells. Giving binimetinib in combination with mFOLFOX6 chemotherapy may be effective in shrinking or stabilizing advanced biliary tract cancers in the 2nd line setting.

Study Chair: Ardaman Shergill, MD, University of Chicago Medicine
Activated: 8/11/2023 | CT.gov Link: https://bit.ly/cmatch-A6

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Preventing Paclitaxel-associated Neuropathy

Alliance A222101: An early phase and phase II clinical trial to evaluate ganglioside-monosialic acid (GM1) for preventing paclitaxel-associated neuropathy
Overview: This phase II trial tests the safety, side effects, and best dose of monosialotetrahexosylganglioside (GM1) and whether it works in reducing or preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) who are receiving treatment with paclitaxel. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Exposure to chemotherapy drugs like paclitaxel may cause a side effect called CIPN, which is a condition of weakness, numbness, and pain from nerve damage (usually in the hands and feet). GM1 is a part of the body's natural system that insulates nerves and helps to protect nerves from damage. Giving GM1 may help reduce or prevent CIPN in breast cancer patients receiving treatment with paclitaxel.

Study Chair: Elizabeth Cathcart-Rake, MD, Mayo Clinic
Activated: 5/31/2023  | CT.gov Link: https://bit.ly/Alliance-A222101

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Colon Cancer

Alliance A022004: Randomized trial of consolidation targeted adjuvant therapy with encorafenib and cetuximab versus usual care for patients with stage II/III BRAF V600E colon cancer
Overview: This phase II/III trial compares 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.

Study Chair: Rona Yaeger, MD, Memorial Sloan Kettering Cancer Center
Activated: 5/30/2023  | CT.gov Link: https://bit.ly/Alliance-A022004

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Triple-Negative Breast Cancer

Alliance A012103: OptimICE-pCR: De-escalation of therapy in early-stage TNBC patients who achieve pCR after neoadjuvant chemotherapy with checkpoint inhibitor therapy
Overview: The phase III trial compares the effect of pembrolizumab to observation for the treatment of patients with early-stage triple-negative breast cancer who achieved a pathologic complete response after preoperative chemotherapy in combination with pembrolizumab. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial may help researchers determine if observation will result in the same risk of cancer coming back as pembrolizumab after surgery in triple-negative breast cancer patients who achieve pathologic complete response after preoperative chemotherapy with pembrolizumab.

Study Chair: Sara Tolaney, MD, Dana-Farber Cancer Institute
Activated: 5/10/2023  | CT.gov Link: https://bit.ly/Alliance-A012103

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Advanced Dedifferentiated Liposarcoma

Alliance A092107: A randomized phase 2 trial with a safety lead-in to evaluate palbociclib versus palbociclib and cemiplimab for the treatment of advanced dedifferentiated liposarcoma
Overview: This phase II trial compares the effect of treatment with palbociclib alone to treatment with palbociclib plus cemiplimab for treating patients with dedifferentiated liposarcoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Palbociclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Cemiplimab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. The combination of these two drugs may be more effective in shrinking or stabilizing advanced dedifferentiated liposarcoma compared to palbociclib alone.

Study Chair: Matthew Ingham, MD, Columbia University
Activated: 3/24/2023  | CT.gov Link: https://bit.ly/Alliance-A092107

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Sarcomatoid Mesothelioma

Alliance A082101: Multimodality immunotherapy in sarcomatoid mesothelioma
Overview: This phase II trial evaluates the safety and effectiveness of giving immunotherapy (nivolumab and ipilimumab) before surgery for controlling disease in patients with stage I-IIIa sarcomatoid mesothelioma. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving immunotherapy before surgery may be more effective at controlling disease in patients with sarcomatoid mesothelioma than giving immunotherapy alone.

Study Chair: Aaron Mansfield, MD, Mayo Clinic
Activated: 3/14/2023  | CT.gov Link: https://bit.ly/Alliance-A082101

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B-cell Acute Lymphoblastic Leukemia

Alliance A042001: A randomized phase II study comparing inotuzumab plus chemotherapy versus standard chemotherapy in older adults with philadelphia-chromosome-negative b-cell acute lymphoblastic leukemia
Overview: This phase II trial compares the combination of inotuzumab ozogamicin and chemotherapy to the usual chemotherapy in treating patients with B-cell acute lymphoblastic leukemia or B-cell lymphoblastic lymphoma. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a drug, called CalichDMH. Inotuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD22 receptors, and delivers CalichDMH to kill them. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving inotuzumab ozogamicin with chemotherapy may help shrink the cancer and stop it from returning.

Study Chair: Marlise R. Luskin, MD, MSCE, Dana-Farber Cancer Institute
Activated: 1/11/2023  | CT.gov Link: https://bit.ly/Alliance-A022102

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Gastroesophageal Adenocarcinoma

Alliance A022102: A randomized phase III trial of mFOLFIRINOX +/- nivolumab vs. FOLFOX +/- nivolumab for first-line treatment of metastatic HER2-negative gastroesophageal adenocarcinoma
Overview: This phase III trial compares the effect of modified fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan (mFOLFIRINOX) to modified fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX) for the treatment of advanced, unresectable, or metastatic HER2 negative esophageal, gastroesophageal junction, and gastric adenocarcinoma. The usual approach for patients is treatment with FOLFOX chemotherapy. Chemotherapy drugs 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. Fluorouracil stops cells from making DNA and it may kill tumor cells. Leucovorin is used with fluorouracil to enhance the effects of the drug. Oxaliplatin works by killing, stopping, or slowing the growth of tumor cells. Some patients also receive an immunotherapy drug, nivolumab, in addition to FOLFOX chemotherapy. Immunotherapy may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Irinotecan blocks certain enzymes needed for cell division and DNA repair, and it may kill tumor cells. Adding irinotecan to the FOLFOX regimen could shrink the cancer and extend the life of patients with advanced gastroesophageal cancers.

Study Chair: Haeseong Park, MD, MPH, Dana-Farber Cancer Institute
Activated: 1/11/2023  | CT.gov Link: https://bit.ly/Alliance-A022102

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Metastatic Colorectal Cancer

Alliance A022101: A pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur)
Overview: This phase III trial 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 4 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.

Study Chair: Eric D. Miller, MD, PhD, Ohio State University Comprehensive Cancer Center
Activated: 1/10/2023  | CT.gov Link: https://bit.ly/Alliance-A022101

 

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