Trial Summary
What is the purpose of this trial?To find out if combining pembrolizumab, bevacizumab (or an equivalent biosimilar drug), and low-dose cyclophosphamide can help control high-grade ovarian cancer that has MRD after treatment. The safety of this treatment combination will also be studied.
What data supports the idea that Triple Drug Combo for Advanced Ovarian Cancer is an effective treatment?The available research shows that Bevacizumab, one of the drugs in the Triple Drug Combo, has demonstrated antitumor activity in patients with platinum-resistant ovarian cancer. This means it can help slow down the growth of cancer when other treatments stop working. Bevacizumab has been shown to improve outcomes when used with other chemotherapy drugs, as seen in two large studies where it was used alongside chemotherapy and then as a maintenance treatment. This suggests that the Triple Drug Combo, which includes Bevacizumab, could be effective in treating advanced ovarian cancer.12578
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use other anti-cancer treatments or certain immunosuppressive therapies during the trial. It's best to discuss your specific medications with the trial team.
Is the drug combination of Bevacizumab, Cyclophosphamide, and Pembrolizumab promising for advanced ovarian cancer?Yes, the drug combination shows promise for advanced ovarian cancer. Bevacizumab, when combined with other drugs, has been effective in controlling the disease and prolonging survival, especially in cases where the cancer is resistant to other treatments.2391213
What safety data exists for the triple drug combo treatment for advanced ovarian cancer?Safety data for the components of the triple drug combo treatment, which includes Bevacizumab (Avastin), Cyclophosphamide (Cytoxan, Neosar, Endoxan), and Pembrolizumab (KEYTRUDA, MK-3475), is available from various studies. Bevacizumab has been evaluated in phase II trials, showing mild toxicities like proteinuria, hypertension, and bleeding, with rare but serious adverse effects such as arterial thromboembolism, wound healing complications, and GI perforation. Pembrolizumab's safety was assessed in the KEYNOTE-028 trial, focusing on PD-L1-positive advanced ovarian cancer. Cyclophosphamide's safety profile is well-documented in oncology, with known side effects. These studies provide a basis for understanding the safety of these drugs individually, though specific data on their combined use in a triple drug regimen may still be under investigation.2461011
Eligibility Criteria
This trial is for women over 18 with high-grade non-mucinous ovarian cancer, who've had surgery and chemo but still have minimal residual disease. They must not have BRCA mutations or HRD-positive tumors, need good organ function, no recent vaccines or other treatments, and can't be pregnant.Inclusion Criteria
I am a woman over 18 with a specific type of ovarian cancer.
I had surgery to check for cancer after initial treatment was successful.
My ovarian cancer was confirmed by a biopsy during my second surgery.
I have undergone the recommended initial surgery and chemotherapy.
My cancer does not have BRCA mutations and is proficient in DNA repair.
My organ functions are within normal ranges according to recent tests.
Exclusion Criteria
I have another cancer that has been treated or progressed in the last 3 years.
I have or had lung inflammation that needed steroids.
I am currently being treated for an infection.
I have a history of Hepatitis B or an active Hepatitis C infection.
My ovarian cancer is either mucinous or low-grade.
I have had a blood clot in an artery before.
I have no ongoing issues with wounds or abnormal connections in my digestive or urinary systems.
I have had bleeding in my lungs, stomach, or brain.
I have an immune system disorder or I'm on long-term steroids.
My cancer has spread to my brain or its coverings.
I have received an organ or tissue transplant from another person.
My high blood pressure is not well controlled.
My cancer has BRCA mutations or is HRD positive.
I am not using, nor do I plan to use, other cancer treatments like chemotherapy or radiation.
I have previously received treatments targeting T-cell receptors.
I have been diagnosed with HIV.
Treatment Details
The study tests a combination of pembrolizumab (an immunotherapy), bevacizumab (a drug that inhibits blood vessel growth in tumors), and low-dose cyclophosphamide (a chemotherapy) to see if it controls ovarian cancer better after standard treatment.
1Treatment groups
Experimental Treatment
Group I: Pembrolizumab in Combination with Bevacizumab and Oral CyclophosphamideExperimental Treatment3 Interventions
Participants will begin receiving the study drug Pembrolizumab in Combination with Bevacizumab and Oral Cyclophosphamide.
Each study cycle is 21 days.
Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:
🇪🇺 Approved in European Union as Avastin for:
- Colorectal cancer
- Breast cancer
- Non-small cell lung cancer
- Renal cell carcinoma
- Ovarian cancer
🇺🇸 Approved in United States as Avastin for:
- Colorectal cancer
- Non-small cell lung cancer
- Glioblastoma
- Renal cell carcinoma
- Cervical cancer
- Ovarian cancer
🇯🇵 Approved in Japan as Avastin for:
- Colorectal cancer
- Non-small cell lung cancer
- Breast cancer
- Renal cell carcinoma
- Ovarian cancer
🇨🇦 Approved in Canada as Avastin for:
- Colorectal cancer
- Non-small cell lung cancer
- Breast cancer
- Renal cell carcinoma
- Ovarian cancer
Find a clinic near you
Research locations nearbySelect from list below to view details:
MD Anderson Cancer CenterHouston, TX
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Who is running the clinical trial?
M.D. Anderson Cancer CenterLead Sponsor
References
[Optimal therapeutic strategies in ovarian epithelial cancer in 1997]. [2015]"Optimal" chemotherapy for advanced ovarian cancer has constantly evolved over the last 2 decades through the conduct of prospective randomized clinical trials. Because 3 such important trials have recently disclosed provocative results there are reasons to believe in the emergence of new "standard" treatment approaches for this disease towards the end of this century. 1) The Intergroup trial found a survival advantage for intraperitoneal cisplatin as compared to intravenous cisplatin following optimal debulking surgery. 2) In the EORTC-GCCG trial, which recruited patients with bulky disease at completion of primary surgery, survival was prolonged when interval debulking surgery was performed after 3 cycles of chemotherapy. 3) Paclitaxel-cisplatin was associated with a marked survival advantage in comparison with cisplatin-cyclophosphamide in the GOG trial, which enrolled suboptimally debulked patients. These trials clearly have important implications for the future management of ovarian cancer patients and from a health economy point of view: for these reasons, two of them (2 + 3) have been repeated by other groups, and results of these confirmatory trials should be available soon. There are a number of new treatment options for "Platinum-resistant" patients including docetaxel, topotecan, gemcitabine, oxaliplatin: but none of them is "optimal". An active search for new drugs in this setting remains a high priority. Finally, with the expanding knowledge of the molecular biology of cancer in general and ovarian cancer in particular, one can now start thinking of new molecular targets for treatment intervention including transmembrane tyrosine kinase growth factor receptors, matrix metalloproteinases, the vascular endothelial growth factor and so on....
Innovative therapies for advanced ovarian cancer. [2012]The emergence of drug-resistant tumors during therapy for ovarian cancer remains an obstacle to improving long-term outcomes. Active areas of ovarian cancer research include clinical evaluation of non-cross-resistant antineoplastic agents that demonstrated single-agent activity in ovarian cancer during the 1990s: oxaliplatin, the new anthracyclines (epirubicin, liposomal doxorubicin), topotecan, oral etoposide, gemcitabine, and vinorelbine. Most of these new agents are currently being evaluated as a component of doublet and triplet combination regimens for advanced ovarian cancer, with use of sequential alternating doublet regimens gaining interest. The potential role of intraperitoneal therapy continues to be investigated. In addition, there are a variety of innovative treatment strategies on the horizon that are targeted at underlying disease processes, including anticancer vaccines, gene therapy, and antiangiogenic therapy. Based on this multitude of investigational questions and the low cure rates currently achieved, all women with advanced ovarian cancer should be offered participation in clinical trials.
[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. [2008]The standard primary therapy of advanced ovarian cancer consists of platinum derivatives in combination with paclitaxel. In a first report presented at this year's meeting of the American Society of Clinical Oncology (ASCO) docetaxel appeared to be as effective as paclitaxel in combination with carboplatin, while the toxicity profile present some advantages. The addition of a third drug to platinum-taxane-combination does not appear to improve the therapeutic index. According to the data of the ICON1- and ACTION-trial, carboplatin containing chemotherapies are associated with a significant benefit also in early ovarian cancer. Platinum-resistant disease remains a therapeutic challenge, since the available drugs display only limited activity of short duration. Some experimental data suggest evidence for a possible therapeutic role of small molecules that inhibit the epidermal growth factor receptor (OSI-774) or antisense oligonucleotides interfering with EGF-receptor signalling (ISIS 5132). Novel classes of chemotherapeutic agents, including the acylfulvenes and the epothilone-analogues warrant further study in this disease. Multimodal therapies combining cytotoxic agents with antibodies against CA 12-5 or metalloproteinase inhibitors have failed to demonstrate any survival benefit in patients with ovarian cancer. Despite significant progress in the last decade ovarian cancer remains the most lethal gynaecologic malignancy in women in most western countries. Further multicenter clinical studies are needed to better define new therapeutic options.
Experience with bevacizumab in the management of epithelial ovarian cancer. [2015]Müllerian duct adenocarcinomas, in particular epithelial ovarian cancers, continue to represent a major source of female cancer-related morbidity and mortality, despite advances in surgical management and innovations in cytotoxic chemotherapy. Angiogenesis-targeted therapy seems to be appropriate for exploration in these disease processes based on a wealth of evidence from preclinical and molecular epidemiology studies. Bevacizumab is a prototypical agent neutralizing vascular endothelial growth factor (VEGF), a critical angiogenic promoter related to tumor progression, malignant effusions, and prognosis in ovarian cancer. Phase II trials have demonstrated the activity of bevacizumab as a single agent and in combination with other modalities such as low-dose metronomic cyclophosphamide. Historical studies have supported these observations. Unique toxicities have been ascribed to the administration of bevacizumab and other anti-VEGF molecules for patients with this disease and other solid tumors. Although most of these toxicities (such as proteinuria, hypertension, and bleeding) are generally mild, and are either self-limiting or controllable, other adverse effects, though uncommon, may be serious (these include arterial thromboembolism, wound healing complications, and GI perforation or fistulae). Phase III trials are now in progress to determine the role of this drug in primary therapy as an adjunct to platinum-taxane chemotherapy. This article reviews the background and rationale for anti-VEGF therapy of ovarian cancer, summarizes efficacy and safety data from phase II trials and historical studies of bevacizumab in this disease, introduces the implementation of bevacizumab in phase III front-line trials, examines controversial aspects related to anti-VEGF therapy, and proposes future directions regarding bevacizumab and other angiogenic growth factor-targeted therapeutics.
Optimal first-line treatment in ovarian cancer. [2022]Treatment of ovarian cancer remains challenging despite the high complete response rate seen after maximal surgical debulking surgery and platinum-combination chemotherapy. as most patients will relapse and eventually succumb to ovarian cancer, new strategies are urgently required to improve survival. a platinum-taxane combination has been the cornerstone of treatment for >15 years. Better use of these drugs is being explored through scheduling studies, and dose-dense or intraperitoneal (IP) therapies. Further improvements in treatment will most likely come from the integration of optimal chemotherapy with one or more of the hundreds of molecular-targeted agents that could be active in ovarian cancer. The greatest experience has been with anti-angiogenic agents. Two large phase III trials in first-line ovarian cancer have demonstrated a positive effect of bevacizumab when administered concurrently with chemotherapy and then as a maintenance treatment. In this review, we discuss the existing treatments for ovarian cancer and highlight areas of recent progress.
A phase II trial of docetaxel and bevacizumab in recurrent ovarian cancer within 12 months of prior platinum-based chemotherapy. [2021]The efficacy and safety of bevacizumab and docetaxel were evaluated in women who developed recurrent epithelial ovarian, fallopian, or peritoneal cancer within 12 months of platinum-based therapy.
A phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube. [2021]To determine the safety and efficacy of the novel combination of docetaxel, oxaliplatin, and bevacizumab as first-line treatment of advanced cancer of the ovary, peritoneum or fallopian tube after initial debulking surgery.
Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives. [2022]Patients with platinum-resistant ovarian cancer have progression of disease within 6 months of completing platinum-based chemotherapy. While several chemotherapeutic options exist for the treatment of platinum-resistant ovarian cancer, the overall response to any of these therapies is ~10%, with a median progression-free survival of 3-4 months and a median overall survival of 9-12 months. Bevacizumab (Avastin), a humanized, monoclonal antivascular endothelial growth factor antibody, has demonstrated antitumor activity in the platinum-resistant setting and was recently approved by US Food and Drug Administration for combination therapy with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan. This review summarizes key clinical trials investigating bevacizumab for recurrent, platinum-resistant ovarian cancer and provides an overview of efficacy, safety, and quality of life data relevant in this setting. While bevacizumab is currently the most studied and clinically available antiangiogenic therapy, we summarize recent studies highlighting novel alternatives, including vascular endothelial growth factor-trap, tyrosine kinase inhibitors, and angiopoietin inhibitor trebananib, and discuss their application for the treatment of platinum-resistant ovarian cancer.
Platinum-resistant recurrent ovarian cancer with long survival on bevacizumab and gemcitabine. [2022]Platinum-resistant recurrent ovarian cancer has a poor prognosis, but combined therapy with bevacizumab and anticancer agents may be useful. We report a patient with long-term disease control by the combination of bevacizumab and gemcitabine (BEV + GEM). The patient was a 77-year-old woman with high-grade Stage IIIC serous ovarian carcinoma. In 2012, a complete response (CR) was obtained by neoadjuvant and adjuvant chemotherapy using paclitaxel plus carboplatin and tumor debulking surgery. After recurrence in 2013, CR was achieved again with gemcitabine plus carboplatin. In 2014, recurrence was detected again, but CR was achieved by third-line combination therapy with gemcitabine, carboplatin and bevacizumab. In 2015, the third recurrence was found during bevacizumab maintenance therapy. Fourth-line treatment was initiated with BEV + GEM, which has maintained stable disease for 29 months. This is the first report about marked prolongation of survival by BEV + GEM in a patient with platinum-resistant recurrent ovarian cancer.
Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019]To evaluate safety, tolerability, and antitumor activity of pembrolizumab monotherapy in patients with programmed death ligand 1 (PD-L1)-expressing advanced ovarian cancer enrolled in the multicohort, phase Ib KEYNOTE-028 trial.
Efficacy of Bevacizumab Combined with Albumin-Bound Paclitaxel in the Treatment of Platinum-Resistant Recurrent Ovarian Cancer. [2020]To investigate the efficacy and safety of bevacizumab (BEV) combined with albumin-bound paclitaxel (ABP) in the treatment of platinum-resistant recurrent ovarian cancer.
Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. [2022]State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin-paclitaxel or carboplatin-gemcitabine) or the most active non-bevacizumab regimen: carboplatin-pegylated liposomal doxorubicin. The aim of this head-to-head trial was to compare a standard bevacizumab-containing regimen versus carboplatin-pegylated liposomal doxorubicin combined with bevacizumab.
Post hoc analyses of GOG 9923: Does BRCA status affect toxicities?: An NRG oncology study. [2022]To evaluate how women with epithelial ovarian cancer (EOC), dichotomized by BRCA status, tolerate intravenous (IV) or intraperitoneal (IP) chemotherapy given with veliparib and bevacizumab (bev) on a GOG phase I study (GOG 9923, NCT00989651).