Chemoimmunotherapy + Vaccines for Recurrent Ovarian Cancer

Recruiting at 1 trial location

Overseen By Emily Staniszewski

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

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 You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 18-24 weeks

25 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

Is 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. ^{6 7 8 9 10}

How 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. ^{1 2 11 12 13}

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.

Research Team

Robert P Edwards, MD

Principal Investigator

University of Pittsburgh

Eligibility 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.

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

Treatment Details

Interventions

• Cisplatin
• CKM
• DC Vaccine

Trial Overview 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.

Participant Groups

Group I: Cisplatin + Celecoxib + DC Vaccine Experimental Treatment 1 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 Vaccine Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

AIM ImmunoTech Inc.

Industry Sponsor

Trials

15

Recruited

710+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

Findings from Research

In a phase II study involving 59 women with recurrent, platinum-sensitive ovarian cancer, the combination of carboplatin, GM-CSF, and rIFN-gamma1b resulted in a 56% overall response rate, with 17% achieving complete response and 39% partial response.

The treatment was associated with common side effects such as bone marrow suppression and fatigue, but responders reported improved quality of life, suggesting that this regimen may be a promising option for further investigation in ovarian cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Schmeler, KM., Vadhan-Raj, S., Ramirez, PT., et al.[2021]

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

Patients with recurrent epithelial ovarian cancer can be categorized into platinum-sensitive and platinum-resistant groups, which require different management strategies based on their response to initial treatment and duration of treatment-free intervals.

Recent randomized trials have shown that platinum combination re-treatment is beneficial for patients with platinum-sensitive disease, while novel agents are being evaluated for both platinum-sensitive and platinum-resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of recurrent ovarian carcinoma: current status and future directions. Martin, LP., Schilder, RJ.[2022]

The combination of carboplatin and cyclophosphamide is emerging as the preferred treatment for epithelial ovarian cancer due to its effectiveness and lower toxicity compared to cisplatin plus cyclophosphamide, based on several prospective studies.

Current clinical trials are exploring high-dose carboplatin regimens and combinations with other treatments, showing promise in improving survival rates for patients with advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Recent advances in ovarian cancer chemotherapy]. Hatae, M., Onishi, Y., Kume, H., et al.[2018]

The introduction of cisplatin-based combination chemotherapy has significantly improved treatment outcomes for advanced ovarian carcinoma, showing better overall response rates and survival compared to earlier single-agent therapies.

Recent trials indicate that a combination of taxol and cisplatin is superior to cisplatin plus cyclophosphamide, suggesting that this regimen should be the new standard of care for patients with advanced ovarian carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in advanced ovarian carcinoma: current standards of care based on randomized trials. Thigpen, T., Vance, R., Puneky, L., et al.[2022]

In a phase I-II trial involving 33 patients with advanced ovarian cancer, a combination of cisplatin and carboplatin was administered safely at high doses, with a median of six treatment courses, although significant myelosuppression was observed in 45% of patients.

The treatment resulted in a pathologic complete response rate of 22%, indicating some efficacy, but further randomized clinical trials are necessary to compare this regimen against standard chemotherapy options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Piccart, MJ., Nogaret, JM., Marcelis, L., et al.[2019]

In a randomized trial involving 173 patients with advanced ovarian cancer, the combination of cisplatin (DDP) with Adriamycin (ADM) and Cyclophosphamide (CTX) was evaluated for its effectiveness.

The study reported high rates of side effects, with 90% of patients experiencing vomiting, 95% experiencing nausea, and 50% experiencing hair loss (alopecia), indicating that while the treatment may be effective, it also has significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness of cisplatin alone and in combination within the scope of primary therapy of ovarian cancer. Results of a prospective multicenter study]. Richter, P., Krafft, W., Müller, U., et al.[2013]

In a Phase I study involving 40 patients with urologic and gynecologic cancers, cis-diamminedichloroplatinum(II) (CIS-DDP) was found to have manageable side effects, primarily nausea, vomiting, and anorexia, which resolved quickly after stopping the treatment.

The study indicated low levels of hematopoietic and renal toxicities, with no reported cases of hearing disturbances or tinnitus, suggesting a favorable safety profile for CIS-DDP at doses of 50 mg/m2 for single administration and 20 mg/m2/day for five consecutive days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013]

Cisplatin (CDDP) has been a key treatment for various cancers since 1972, but its use is limited by significant toxicities, particularly renal impairment.

Carboplatin (CBDCA), a second-generation analogue of cisplatin, has shown reduced renal toxicity and is effective against advanced cancers, although it can cause myelosuppression, particularly affecting platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Second-generation cisplatin analogs]. Ariyoshi, Y., Ota, K.[2013]

Intraperitoneal carboplatin (IP-Ca) treatment in 31 ovarian cancer patients with minimal residual disease after chemotherapy showed promising results, with 2 patients achieving a complete pathological response lasting over 33 months.

The maximum tolerable dose of IP-Ca was determined to be 300 mg/m2, with thrombocytopenia being the main dose-limiting toxicity, affecting 27% of patients at the highest dose, while side effects were generally mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal carboplatin in the treatment of minimal residual ovarian cancer. Pfeiffer, P., Bennedbaek, O., Bertelsen, K.[2019]

The study developed a method to create synthetic oligopeptides from unique ovarian cancer biomarkers, which could lead to highly specific immune responses against ovarian cancer.

These oligopeptides are designed to be non-crossreactive, potentially enhancing their effectiveness for immunodiagnostics, immunoprevention, and immunotherapy in ovarian cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oligopeptides for Immunotherapy Approaches in Ovarian Cancer Treatment. Kanduc, D.[2020]

A 71-year-old woman with chemoresistant ovarian cancer showed significant clinical improvement after receiving four rounds of neoantigen peptide-loaded dendritic cell (DC) vaccinations, including reduced CA-125 levels and decreased tumor cells in ascites, without any adverse reactions.

The treatment also led to an immune response, as evidenced by the detection of neoantigen-specific T cells in her blood and tumor, suggesting that this personalized immunotherapy could be a promising option for patients with limited treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Morisaki, T., Hikichi, T., Onishi, H., et al.[2021]

In a phase 1/2 trial involving patients with platinum-resistant p53-positive epithelial ovarian cancer, the combination of gemcitabine, Pegintron, and a p53 synthetic long peptide vaccine was well-tolerated, with no dose-limiting toxicities reported.

The treatment combination effectively enhanced immune responses, as evidenced by increased circulating CD4+ and CD8+ T-cells and strong p53-specific T-cell responses, suggesting a promising approach for integrating chemotherapy with immunotherapy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1/2 study combining gemcitabine, Pegintron and p53 SLP vaccine in patients with platinum-resistant ovarian cancer. Dijkgraaf, EM., Santegoets, SJ., Reyners, AK., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

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]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Management of recurrent ovarian carcinoma: current status and future directions. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

[Recent advances in ovarian cancer chemotherapy]. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Chemotherapy in advanced ovarian carcinoma: current standards of care based on randomized trials. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

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]

7. Germany pubmed.ncbi.nlm.nih.gov

[Effectiveness of cisplatin alone and in combination within the scope of primary therapy of ovarian cancer. Results of a prospective multicenter study]. [2013]

8. Japan pubmed.ncbi.nlm.nih.gov

[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013]

9. Japan pubmed.ncbi.nlm.nih.gov

[Second-generation cisplatin analogs]. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Intraperitoneal carboplatin in the treatment of minimal residual ovarian cancer. [2019]

11. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Oligopeptides for Immunotherapy Approaches in Ovarian Cancer Treatment. [2020]

12. England pubmed.ncbi.nlm.nih.gov

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]

13. United States pubmed.ncbi.nlm.nih.gov

A phase 1/2 study combining gemcitabine, Pegintron and p53 SLP vaccine in patients with platinum-resistant ovarian cancer. [2022]