GEN-1 + Chemo + Bevacizumab for Ovarian Cancer
(MRD Trial)
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Imunon
Must not be taking: Corticosteroids, Immunosuppressants
Disqualifiers: Autoimmune disease, HIV, Hepatitis, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
This trial is testing if adding a new drug, IMNN-001, to standard cancer treatments can make the treatment more effective for patients. The standard treatments include chemotherapy and Bevacizumab, which are commonly used for various cancers such as colorectal, lung, and ovarian cancers.
Will I have to stop taking my current medications?
The trial requires that any hormonal therapy directed at the malignant tumor be stopped at least one week before the first treatment. However, hormone replacement therapy can continue. The protocol does not specify other medication restrictions, but you should discuss your current medications with the trial team.
What data supports the effectiveness of the drug combination GEN-1, Bevacizumab, and chemotherapy for ovarian cancer?
Research shows that combining Bevacizumab with chemotherapy drugs like paclitaxel and carboplatin can improve progression-free survival (the time during which the cancer does not get worse) in ovarian cancer patients. Bevacizumab has also shown antitumor activity in cases where the cancer is resistant to platinum-based treatments.12345
Is the combination of GEN-1, chemotherapy, and bevacizumab safe for treating ovarian cancer?
Bevacizumab, when combined with chemotherapy drugs like carboplatin and paclitaxel, has been studied for safety in treating ovarian cancer. Common side effects include high blood pressure, bleeding, and protein in the urine, which are usually mild and manageable, but there can be serious risks like blood clots and digestive system issues. These findings are based on studies of bevacizumab with chemotherapy in ovarian cancer patients.36789
What makes the drug combination of GEN-1, chemotherapy, and Bevacizumab unique for treating ovarian cancer?
This treatment is unique because it combines GEN-1, a novel agent, with chemotherapy and Bevacizumab, which targets blood vessel growth in tumors. Bevacizumab has shown to improve progression-free survival in ovarian cancer when added to standard chemotherapy, offering a new option for patients with advanced disease.1011121314
Research Team
AJ
Amir Jazaeri, MD
Principal Investigator
University of Texas MD Anderson Center
Eligibility Criteria
This trial is for adults with advanced ovarian, fallopian tube, or primary peritoneal cancer at FIGO stage III or IV. They must be recommended for neoadjuvant therapy and have high grade serous adenocarcinoma confirmed by laparoscopy. Participants need proper organ function, no severe illnesses including recent COVID-19, no hormonal cancer therapies within a week before the trial starts, and an ECOG performance status of 0-1. Women must not be pregnant or breastfeeding and agree to use contraception.Inclusion Criteria
I haven't had a serious illness, infection needing strong antibiotics, or COVID-19 in the last 4 weeks.
My ovarian cancer is a specific type called high grade serous adenocarcinoma.
Subjects must have satisfactory results for the baseline laboratory analyses and diagnostic procedures as specified in the protocol
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Exclusion Criteria
I haven't had radiation in my abdomen or pelvis but may have had it for breast, head and neck, or skin cancer over three years ago without recurrence.
I have previously been treated with IMNN-001.
Subjects who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to IMNN-001 or other drugs used in this study
See 14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Neoadjuvant Chemotherapy
Participants receive neoadjuvant chemotherapy with Paclitaxel and Carboplatin every 21 days for 4 to 6 cycles, with BEV included in certain cycles.
12-18 weeks
Interval Cytoreductive Surgery (ICS)
Interval cytoreductive surgery is performed 3-4 weeks after the last dose of neoadjuvant chemotherapy.
3-4 weeks
Adjuvant Chemotherapy
Participants receive adjuvant chemotherapy with Paclitaxel and Carboplatin, with BEV included in certain cycles, for 3 additional cycles.
9 weeks
Maintenance Therapy
BEV is administered every 3 weeks as a single agent until disease progression or unacceptable toxicity, for up to an additional 18 cycles.
54 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment.
8 months
Treatment Details
Interventions
- Bevacizumab (Angiogenesis Inhibitor)
- Carboplatin (Chemotherapy)
- GEN1 (Gene Therapy)
- Paclitaxel (Chemotherapy)
Trial OverviewThe study tests adding IMNN-001 (GEN-1) to standard chemotherapy with Bevacizumab versus chemotherapy with Bevacizumab alone in patients with newly diagnosed advanced ovarian-related cancers. It's a phase I/II randomized open-label trial assessing safety, dosing efficacy, and biological activity.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Chemotherapy + BEV + IMNN-001 (Experimental)Experimental Treatment4 Interventions
Chemotherapy (neoadjuvant and adjuvant): Paclitaxel 175 mg/m2 IV followed by carboplatin AUC 5-6 IV starting on C1D1. During the neoadjuvant period, there will be from 4 to 6 cycles repeated every 21 days.
BEV 15 mg/kg IV administration will be included with each cycle except during the cycles around time of surgery. During maintenance, BEV will be administered every 3 weeks as a single agent until disease progression or unacceptable toxicity for a maximum of an additional 18 cycles. In total, BEV may be administered up to 24 cycles. FDA approved BEV biosimilars may be used in this study in place of BEV.
IMNN-001 80 mg/m2 IP will be administered weekly beginning C1D15 and continue weekly through the last cycle of adjuvant therapy. At the conclusion of chemotherapy, GEN-1 will be administered every 21 days with BEV in subjects who are BRCA-/HRP until disease progression or unacceptable toxicity for up to an additional 18 cycles.
Group II: Chemotherapy + BEV (Control)Experimental Treatment3 Interventions
Chemotherapy (neoadjuvant and adjuvant): Paclitaxel 175 mg/m2 IV followed by carboplatin AUC 5-6 IV starting on C1D1. During the neoadjuvant period, there will be from 4 to 6 cycles (at the Investigator's discretion, having an additional C4+1 and C4+2) repeated every 21 days.
BEV 15 mg/kg IV administration will be included with each cycle EXCEPT the following cycles: \[1\] Cycle 1, \[2\] the last cycle of neoadjuvant therapy immediately preceding ICS, and \[3\] the first cycle of adjuvant chemotherapy (i.e., first cycle after ICS). During the maintenance phase, BEV 15 mg/kg will be administered every 3 weeks as a single agent until disease progression or unacceptable toxicity for a maximum of an additional 18 cycles. In total, BEV may be administered up to 24 cycles. FDA approved BEV biosimilars may be used in this study in place of BEV.
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:
Memorial Sloan Kettering Cancer CenterNew York, NY
Johns Hopkins Medicine SKCCCBaltimore, MD
University of Texas MD Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
Imunon
Lead Sponsor
Trials
16
Patients Recruited
1,600+
Breakthrough Cancer Research
Collaborator
Trials
2
Patients Recruited
250+
Break Through Cancer Foundation
Collaborator
Trials
1
Patients Recruited
50+
References
Effect of bevacizumab plus paclitaxel and carboplatin regimen on prognostic survival of ovarian cancer patients. [2023]To investigate the efficacy of bevacizumab, paclitaxel and carboplatin in the treatment of ovarian cancer (OC) and the impact on patients' prognosis.
Treatment of ovarian cancer: current status. [2015]Cytoreductive surgery followed by platinum-based combination chemotherapy has been standard therapy for patients with advanced epithelial ovarian cancer. Despite advances in surgery and in the development of a less toxic platinum compound (carboplatin), most patients with advanced ovarian cancer are not cured. Current clinical trials focus on dose-intense chemotherapy, routes and schedules of administration, and the role of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ). This novel agent has been shown to be highly active in patients with platinum-resistant ovarian cancer. Paclitaxel together with platinum (ie, cisplatin or carboplatin) combinations are now being tested in prospective randomized trials and in pilot studies in previously untreated patients with advanced disease.
Role of front-line bevacizumab in advanced ovarian cancer: the OSCAR study. [2020]Two randomized phase III trials demonstrated the efficacy and safety of combining bevacizumab with front-line carboplatin/paclitaxel for advanced ovarian cancer. The OSCAR (NCT01863693) study assessed the impact of front-line bevacizumab-containing therapy on safety and oncologic outcomes in patients with advanced ovarian cancer in the UK.
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.
Phase III trials of standard chemotherapy with or without bevacizumab for ovarian cancer: a meta-analysis. [2021]Platinum-based standard chemotherapy improves survival of ovarian cancer (OC), but the five-year survival rate remains below 50%. Antiangiogenic agents (7.5 or 15 mg/kg Bevacizumab, Bev) plus to standard chemotherapy improve progression-free survival (PFS) not overall survival (OS) in completed randomized controlled trials (RCTs). The efficacy and safety of two doses of Bev + standard chemotherapy remain controversial.
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.
Paclitaxel (Taxol) treatment for refractory ovarian cancer: phase II clinical trial. [2019]Our aim was to determine the efficacy and toxicity of paclitaxel in the treatment of refractory and platinum-resistant epithelial ovarian cancer.
Arthralgia in patients with ovarian cancer treated with bevacizumab and chemotherapy. [2021]Chemotherapy with carboplatin, paclitaxel, and bevacizumab is the standard therapy for patients with advanced stage ovarian cancer wild-type BRCA after primary surgery. The most frequent side effects of bevacizumab in this setting are hypertension, thrombosis, hemorrhage, and proteinuria, while arthralgia has been poorly described.
Prospective non-interventional BELOVA/BGOG-ov16 study on safety of frontline bevacizumab in elderly patients with FIGO stage IV ovarian cancer: a study of the Belgian and Luxembourg Gynaecological Oncology Group. [2022]Because elderly patients with ovarian cancer are underrepresented in randomized studies, this study aimed to expand our knowledge on the safety and effectiveness of frontline treatment with bevacizumab in combination with standard carboplatin and paclitaxel chemotherapy in patients aged 70 years and older with a diagnosis of Federation of Gynecology and Obstetrics (FIGO) stage IV ovarian cancer in routine clinical practice in Belgium.
Bevacizumab and ovarian cancer. [2021]Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that targets vascular endothelial growth factor-A, and is indicated in the treatment of various tumors (colon, lung, renal, and glioblastoma). It has been recently approved for the treatment of ovarian cancer in various countries. This review summarizes the activity and toxicity of bevacizumab in the treatment of ovarian cancer, both as single-agent drug and in combination with cytotoxic chemotherapy. As a single-agent drug, it has shown response rates of 16-21% in the treatment of recurrent ovarian cancer. Two phase III randomized trials have been published evaluating the addition of bevacizumab to standard chemotherapy as front-line treatment of advanced ovarian cancer. In addition, trials evaluating the combination with chemotherapy in recurrent ovarian cancer (platinum-sensitive and platinum-resistant disease) have also been reported. All these trials showed a statistically significant improvement in progression-free survival although no improvement in overall survival has been reported. The main adverse event is hypertension. Other serious, but uncommon adverse events include gastrointestinal perforation as well as renal and central nervous system toxicity.
Bevacizumab with Chemotherapy as a First-Line Treatment for Advanced Ovarian Cancer in a Serbian Cohort. [2023]Background and Objectives: For stage IIIb-IV ovarian cancer, bevacizumab-containing treatment is considered the standard of care. The purpose of this study was to evaluate the efficacy of bevacizumab in combination with carboplatin and paclitaxel as a first-line treatment for advanced ovarian cancer. Materials and Methods: Eligible patients had stage IIIc-IV ovarian cancer according to the International Federation of Gynecology and Obstetrics with no clinical signs or symptoms of gastrointestinal obstruction or a history of abdominal fistulae, gastrointestinal perforation, or intra-abdominal abscess or evidence of rectosigmoid involvement by pelvic examination, bowel involvement on computed tomography, or clinical symptoms of bowel obstruction in the previous 6 months. After debulking surgery, the patients received 175 mg/m2 paclitaxel and carboplatin (AUC 6) for the first six cycles and 7.5 mg/kg bevacizumab every three weeks up to 17 cycles until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was progression-free survival. The secondary endpoint was overall survival. Results: Between April 2017 and March 2020, 35 patients began study treatment. Bevacizumab was administered at 7.5 mg/kg in all the patients and for more than 7.5 months in 70% of them. The median progression-free survival was 20 months (95% CI: 16-23). The median overall survival was not reached. Conclusions: This was, to our knowledge, the first trial in Serbia to show progression-free survival and overall survival of combination regimens in advanced ovarian cancer. Based on the observed progression-free survival, bevacizumab combined with chemotherapy should be considered as a standard option in advanced ovarian cancer.
Bevacizumab and its use in epithelial ovarian cancer. [2019]Bevacizumab is a monoclonal antibody that binds to VEGF, a circulating protein involved in the promotion of angiogenesis and probably tumor growth and progression. Bevacizumab has demonstrated anticancer activity in several cancers, either combined with chemotherapy or when used as a single agent, and has been approved by the US FDA as a treatment for several cancers. As VEGF has been implicated in ovarian cancer progression and ascites formation, and high levels of VEGF have been found in plasma and ascites in women with ovarian cancer, bevacizumab has been tested as an anticancer therapy in ovarian cancer. Documented single-agent activity of bevacizumab in recurrent ovarian cancer has led to combination studies with both biologic agents as well as other chemotherapy agents in both recurrent and newly diagnosed cancer. One trial in patients with recurrent, heavily pretreated ovarian cancer demonstrated a higher than predicted risk of gastrointestinal perforation, and although a lower incidence of gastrointestinal perforation has been reported in less heavily pretreated patients, patients and their physicians must be aware of this risk. Upfront studies testing the impact of adding bevacizumab to carboplatin and paclitaxel chemotherapy for the treatment of newly diagnosed cancer are currently underway, and one Phase III randomized study (Gynecologic Oncology Group study 218) was recently presented and will be discussed in this article.
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.
Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. [2019]Bevacizumab (Avastin®) is a recombinant, humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody that neutralizes the biological activity of VEGF and inhibits tumor angiogenesis. In the EU, in adult patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer, bevacizumab (in combination with carboplatin and paclitaxel) is approved for the first-line treatment of advanced disease and (in combination with carboplatin and gemcitabine) is approved for the treatment of patients with first recurrence of platinum-sensitive disease who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents. This article summarizes the pharmacology of bevacizumab and reviews the efficacy and tolerability of bevacizumab combination therapy in well-designed clinical studies in these indications. The addition of bevacizumab to first-line carboplatin plus paclitaxel, followed by bevacizumab maintenance therapy significantly prolonged progression-free survival in women with newly-diagnosed advanced disease (GOG-0218 and ICON7 studies). Progression-free survival was also significantly prolonged after second-line treatment with bevacizumab in combination with carboplatin and gemcitabine, followed by maintenance treatment with bevacizumab alone in women with recurrence (≥ 6 months after front-line platinum-based therapy) of platinum-sensitive disease (OCEANS study). Bevacizumab combination therapy had a generally acceptable tolerability profile in these studies, with the nature of adverse events generally similar to that observed in previous clinical trials in patients with other solid tumors. Although several unanswered questions remain, such as the optimal dosage and duration of treatment, current evidence suggests that bevacizumab combination therapy extends the treatment options available for patients with ovarian cancer.