Chemoimmunotherapy + Vaccines for Recurrent Ovarian Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byRobert P Edwards, MD
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Roswell Park Cancer Institute
Must be taking: Neoadjuvant chemotherapy
Must not be taking: Immunosuppressants, Corticosteroids
Disqualifiers: Autoimmune diseases, Immunodeficiency, Pregnancy, others
Stay on Your Current Meds
No Placebo Group
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?This study will evaluate the immunologic and potential clinical effectiveness of intensive locoregional sequential intraperitoneal (IP) cisplatin (IPC) with intravenous (iv) paclitaxel followed by peritoneal infusion of a chemokine modulatory (CKM) regimen composed of a cocktail of IP rintatolimod and interferon-alpha (IFNα) for patients with advanced stage ovarian cancer (III-IV) at primary neoadjuvant setting.
In the safety phase I phase, we determined the tolerable dose of IPC-CKM. In this phase 2 we will add intradermal (ID) autologous αDC1 vaccines (known to be nontoxic) to the tolerable IPC-CKM regimen. The effectiveness will be determined by rate of complete pathologic response.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive drugs or have certain allergies, you may not be eligible to participate.
What data supports the effectiveness of the treatment Chemoimmunotherapy + Vaccines for Recurrent Ovarian Cancer?
Research shows that platinum-based drugs like cisplatin are effective in treating ovarian cancer, especially when combined with other agents. Studies have demonstrated that combinations of platinum compounds with other drugs can improve response rates and survival in ovarian cancer patients.
12345Is the chemoimmunotherapy treatment for recurrent ovarian cancer safe for humans?
The treatment involving cisplatin (also known as CDDP) and carboplatin has been studied for safety in humans, showing that it can be given safely at certain doses with close monitoring. Common side effects include nausea, vomiting, and blood-related issues like low white blood cell and platelet counts, while more serious effects can include kidney and nerve damage.
678910How is the treatment of Chemoimmunotherapy + Vaccines for Recurrent Ovarian Cancer different from other treatments?
This treatment is unique because it combines chemotherapy with immunotherapy, using vaccines to target specific cancer markers, potentially enhancing the immune system's ability to fight ovarian cancer. Unlike standard treatments, it aims to personalize therapy by using vaccines that stimulate the body's immune response against cancer-specific proteins.
12111213Eligibility Criteria
This trial is for advanced stage (III-IV) ovarian, tubal, or peritoneal cancer patients who haven't had chemo before. They must be fit enough for surgery and chemotherapy without significant health issues like kidney damage or bowel obstruction. Women of childbearing age need a negative pregnancy test and must use birth control.Inclusion Criteria
My cancer is advanced ovarian, tubal, or peritoneal carcinoma.
I can carry out all my usual activities without help.
I am willing to undergo a procedure to collect white blood cells.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive up to 6-8 cycles of intensive locoregional chemoimmunotherapy with intradermal autologous αDC1 vaccines and oral celecoxib
18-24 weeks
1 visit per cycle (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
8 weeks
Participant Groups
The study tests intensive chemoimmunotherapy with intraperitoneal Cisplatin and IV Paclitaxel followed by a chemokine modulatory regimen plus autologous αDC1 vaccines in patients receiving first-line neoadjuvant therapy to see if it improves treatment response.
2Treatment groups
Experimental Treatment
Group I: Cisplatin + Celecoxib + DC VaccineExperimental Treatment1 Intervention
Cisplatin 50 mg/m2 by IP once per cycle (21 days) + celecoxib daily 200 mg by mouth daily + intranodal vaccine injections once per cycle
Group II: Cisplatin + CKM + Celecoxib + DC VaccineExperimental Treatment1 Intervention
Cisplatin 50 mg/m2 by IP once per cycle (21 days) + celecoxib daily 200 mg by mouth daily + IFN by IP once per cycle + rintatolimod 200 mg by IP once per cycle + intranodal vaccine injections once per cycle
Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Platinol for:
- Testicular cancer
- Ovarian cancer
- Cervical cancer
- Bladder cancer
- Head and neck cancer
- Esophageal cancer
- Lung cancer
- Mesothelioma
- Brain tumors
- Neuroblastoma
🇺🇸 Approved in United States as Platinol for:
- Testicular cancer
- Ovarian cancer
- Cervical cancer
- Bladder cancer
- Head and neck cancer
- Esophageal cancer
- Lung cancer
- Mesothelioma
- Brain tumors
- Neuroblastoma
🇨🇦 Approved in Canada as Platinol for:
- Testicular cancer
- Ovarian cancer
- Cervical cancer
- Bladder cancer
- Head and neck cancer
- Esophageal cancer
- Lung cancer
- Mesothelioma
- Brain tumors
- Neuroblastoma
🇯🇵 Approved in Japan as Platinol for:
- Testicular cancer
- Ovarian cancer
- Cervical cancer
- Bladder cancer
- Head and neck cancer
- Esophageal cancer
- Lung cancer
- Mesothelioma
- Brain tumors
- Neuroblastoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UPMC CancerCenter at Magee-Womens Hospital of UPMCPittsburgh, PA
Hillman Cancer CenterPittsburgh, PA
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Who Is Running the Clinical Trial?
Roswell Park Cancer InstituteLead Sponsor
AIM ImmunoTech Inc.Industry Sponsor
National Cancer Institute (NCI)Collaborator
University of PittsburghCollaborator
References
A phase II study of GM-CSF and rIFN-gamma1b plus carboplatin for the treatment of recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer. [2021]To evaluate the efficacy and toxicity of carboplatin, granulocyte-macrophage colony-stimulating factor (GM-CSF) and recombinant interferon gamma 1b (rIFN-gamma1b) in women with recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer.
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.
Management of recurrent ovarian carcinoma: current status and future directions. [2022]The majority of patients who present with epithelial ovarian cancer respond well to the initial treatment, but will ultimately experience a recurrence of their disease. Chemotherapy can palliate symptoms of disease recurrence, and there is some evidence that it also can improve survival. Recurrent ovarian carcinoma is divided into two subsets of patients: those with platinum-sensitive disease and those with platinum-resistant disease. Management for these two groups has diverged in the last few years, as evidence accrues that the response to treatment and duration of treatment-free interval after completion of front-line therapy impacts the prognosis and the treatment choice for these patients. Recent randomized trials have demonstrated a benefit for platinum combination re-treatment in patients with platinum-sensitive disease. Additionally, there are multiple single-agent trials evaluating novel agents for patients with platinum-resistant as well as platinum-sensitive disease. This review will discuss the role of chemotherapy in recurrent disease, describe the various agents used in this setting, and touch on the role of biologic agents in recurrent epithelial ovarian carcinoma.
[Recent advances in ovarian cancer chemotherapy]. [2018]The standard approach for epithelial ovarian cancer has been maximum cytoreductive surgery followed by combination therapy. Several prospective control studies individually failed to demonstrate improved survival advantage for the Adriamycin containing combination compare with cisplatin plus cyclophosphamide. The two drug combination of carboplatin plus cyclophosphamide will be thought to become the treatment of choice, because it is equally effective as and less toxic than a regimen of cisplatin plus cyclophosphamide. Clinical trials are also in progress with more dose-intense regimens based on considerable retrospective evidence that survival is correlated with the dose intensity of platinum compounds. Currently, high dose carboplatin plus Gm-CSF, two-drug combination of carboplatin and cisplatin and super high dose carboplatin combined with autologous bone marrow transplantation are undergoing clinical trials. Taxol and taxotere, most important cancer drugs after emergence of cisplatin compound, has been shown to have clinical activity in drug resistant ovarian cancer patients. Majority of patients even with advanced germ cell tumors of the ovary is now cured because of the development of effective platinum-based combination chemotherapy of PVB or BEP.
Chemotherapy in advanced ovarian carcinoma: current standards of care based on randomized trials. [2022]The mainstay of the treatment of advanced (stage III or IV) ovarian carcinoma is systemic therapy. The following review bases conclusions regarding standards of care on large, randomized trials of chemotherapy in advanced ovarian carcinoma. As of 1976, "standard" chemotherapy was single alkylating agent usually with melphalan. Studies of combination chemotherapy failed to show superiority over single alkylating agent until the introduction of cisplatin. The Gynecologic Oncology Group conducted a series of two trials in patients with large-volume disease, the first randomizing patients to either single-agent melphalan or a combination of doxorubicin and cyclophosphamide and the second to doxorubicin plus cyclophosphamide with or without cisplatin. These studies demonstrated superiority for the cisplatin-based combination in terms of overall response rate, clinical complete response rate, progression-free survival, and overall survival. Subsequent randomized trials demonstrated several important facts. First, platinum-based combinations yielded results superior to single-agent cisplatin. Second, a two-drug combination of cisplatin plus cyclophosphamide provides benefit equivalent to the three-drug combination of the same two drugs plus doxorubicin. Third, substitution of carboplatin for cisplatin yields similar results. Finally, dose escalation of chemotherapy by a factor of 2 does not offer a therapeutic advantage. The next major advance after the introduction of the platinum compounds was the demonstration of the activity of taxol, a new agent with a unique mechanism of action and apparent clinical non-cross-resistance with the platinum compounds. A recently completed GOG trial of cisplatin plus cyclophosphamide versus cisplatin plus taxol in patients with large-volume disease shows that the taxol-based combination has a superior overall response rate, clinical complete response rate, rate of achieving a state of no gross residual disease at second-look laparotomy, and progression-free survival. Survival analysis awaits maturation of the data, but the control arm has already been shown to have a median survival of 23.2 months with the median not yet reached for the taxol-based arm. These data suggest that a combination of taxol plus cisplatin should be considered the standard of care for patients with advanced ovarian carcinoma. Ongoing trials seek to define further the role of taxol in frontline chemotherapy for ovarian carcinoma. In conclusion, the standard chemotherapy for advanced ovarian carcinoma should be considered a combination of taxol plus a platinum compound.
Cisplatin combined with carboplatin: a new way of intensification of platinum dose in the treatment of advanced ovarian cancer. Belgian Study Group for Ovarian Carcinoma. [2019]We performed a phase I-II trial of escalating doses of cisplatin (CDDP: 50-100 mg/m2 per course) plus carboplatin (CBDCA: 300-400 mg/m2 per course) as a potential way in which to maximize platinum doses without causing excessive toxic effects in patients with advanced ovarian cancer. Thirty-three patients with nonoptimally debulked disease of FIGO (International Federation of Gynecology and Obstetrics) stages IIc-IV [median age: 60 yr; median WHO (World Health Organization) performance status: 2; no prior chemotherapy] received a median of six courses of therapy. CBDCA was infused on day 1 and CDDP on day 2 with an aggressive 48-hour hydration regimen. Myelosuppression was dose-limiting: at the highest dose levels, WHO grade 4 neutropenia and thrombocytopenia led to dose reduction and/or treatment delay in 45% of the patients. Nonhematologic toxic effects included acute nausea and vomiting (97% of the patients), mild alopecia (45%), ototoxic effects (39%), neurotoxic effects (21%), and renal toxic effects (serum creatinine greater than 1.5 mg/dL: 12.5%). The pathologic complete response rate was 22%. We conclude that CBDCA and CDDP can be given safely in combination at reasonably high doses (CBDCA at 300 mg/m2 per course and CDDP at 100 mg/m2 per course) over a 6-month period, provided a close hematologic follow-up is conducted. Randomized clinical trials are needed to define whether this regimen is any better than standard combination chemotherapy.
[Effectiveness of cisplatin alone and in combination within the scope of primary therapy of ovarian cancer. Results of a prospective multicenter study]. [2013]The efficiency of cis Platin (DDP) alone and in combination with Adriamycine (ADM) and Cyclophosphamid (CTX) were evaluated in a prospective randomized trial containing 173 pat. suffering from advanced ovarian cancer (FIGO III/IV). Therapeutic schedule and results: (table; see text) The most side effects concerned vomiting (WHO Grad 2) in 90%, nausea (WHO Grad 2) in 95% and alopecia in 50% out of all pat.
[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013]Phase I study of cis-diamminedichloroplatinum(II) (CIS-DDP) was performed in 7 institution's clinical group using 40 patients with histologically proven urologic and gynecologic malignancies. The most characteristic adverse effects were nausea, vomiting, and anorexia. With the cessation of administration they disappeared within one or two days. Manifestation of hematopoietic and renal toxicities were found low. Hepatotoxicities were slight. In this study there were no cases who showed hearing disturbances and tinnitus, which were reported in rather high percentages. Acceptable doses of CIS-DDP for single and 5 days' consecutive administration were estimated 50 and 20 mg/m2/day respectively.
[Second-generation cisplatin analogs]. [2013]Since the introduction into clinical practice in 1972, cisplatin (CDDP) has assumed an important role in the treatment of various tumors such as testicular, ovarian or pulmonary cancer. Its toxicities include emesis, renal impairment, neuropathy, hearing loss and anemia. In clinical trials renal toxicity has been proved to be dose limiting factor. Thus the total number of courses which may be given is limited. For this reason second-generation CDDP analogues with reduced toxicity have been tried to develop and are reaching clinical testing. A number of studies have now been published relating the results of these trials. The best studied of these analogues is carboplatin (CBDCA, JM-8) which was noted to be less nephrotoxic, but more myelosuppressive than CDDP in preclinical study. Phase I trials have shown that CBDCA is relatively free of renal toxicity and that its dose limiting factor is myelosuppression, especially thrombocytopenia. In phase II trials CBDCA has been shown to be an active agent in advanced carcinomas of the ovary, head and neck, lung and urogenital organs. Similar results have been obtained in clinical trials of iproplatin (CHIP, JM-9) which is synthesized as an analogue of CDDP. Two other analogues developed in Japan have been evaluated to be active for various mouse tumors in preclinical studies. Phase I trials of these agents is now ongoing.
Intraperitoneal carboplatin in the treatment of minimal residual ovarian cancer. [2019]Thirty-one ovarian cancer patients with minimal residual disease after intravenous cisplatin combination chemotherapy were treated with intraperitoneal carboplatin (IP-Ca). The dose of IP-Ca was escalated from 150 to 350 mg/m2. Twenty-two patients received at least three courses of IP-Ca and were evaluable for efficacy. Third-look laparotomy was done in 10 patients. Two patients obtained a complete pathological response (CPR) lasting 33+ and 41+ months, respectively; 8 patients had minimal residual disease. Median survival for all patients was 14+ months. All patients were eligible for toxicity. Maximum tolerable dose in these heavily pretreated patients was 300 mg/m2 IP-Ca. The dose-limiting toxicity was thrombocytopenia; in 27% of the patients who received 350 mg/m2 IP-Ca, WHO grade 4 thrombocytopenia was seen. No patient had WHO grade 4 leukopenia. Subjective side effects consisted of mild nausea and vomiting (WHO). In conclusion, IP-Ca can produce CPR in heavily pretreated patients with only minor side effects.
Oligopeptides for Immunotherapy Approaches in Ovarian Cancer Treatment. [2020]Anti-ovarian cancer vaccines based on minimal immune determinants uniquely expressed in ovarian cancer biomarkers appear to promise a high level of sensitivity and specificity for ovarian cancer immunodiagnostics, immunoprevention, and immunotherapy.
Intranodal Administration of Neoantigen Peptide-loaded Dendritic Cell Vaccine Elicits Epitope-specific T Cell Responses and Clinical Effects in a Patient with Chemorefractory Ovarian Cancer with Malignant Ascites. [2021]Chemorefractory ovarian cancer has limited therapeutic options. Hence, new types of treatment including neoantigen-specific immunotherapy need to be investigated. Neoantigens represent promising targets for personalized cancer immunotherapy. We here describe the clinical and immunological effects of a neoantigen peptide-loaded DC-based immunotherapy in a patient with recurrent and chemoresistant ovarian cancer. A 71-year-old female patient with chemorefractory ovarian cancer and malignant ascites received intranodal vaccination of DCs loaded with four neoantigen peptides that were predicted by our immunogenomic pipeline. Following four rounds of vaccinations with this therapy, CA-125 levels were remarkably declined and tumor cells in the ascites were also decreased. Concordantly, the tumor-related symptoms such as respiratory discomfort improved without any adverse reactions. The reactivity against one HLA-A2402-restricted neoantigen peptide derived from a mutated PPM1 F protein was detected in lymphocytes from peripheral blood by IFN-γ ELISPOT assay. Furthermore, the neoantigen (PPM1 F mutant)-specific TCRs were detected in the tumor-infiltrating T lymphocytes post-vaccination. Our results showed that vaccination with intranodal injection of neoantigen peptide-loaded DCs may have clinical and immunological impacts on cancer treatment.
A phase 1/2 study combining gemcitabine, Pegintron and p53 SLP vaccine in patients with platinum-resistant ovarian cancer. [2022]Preclinical tumor models show that chemotherapy has immune modulatory properties which can be exploited in the context of immunotherapy. The purpose of this study was to determine the feasibility and immunogenicity of combinations of such an immunomodulatory chemotherapeutic agent with immunotherapy, p53 synthetic long peptide (SLP) vaccine and Pegintron (IFN-α) in patients with platinum-resistant p53-positive epithelial ovarian cancer (EOC).