Chemoimmunotherapy + Vaccines for Recurrent Ovarian Cancer

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a combination of chemotherapy, immunotherapy, and vaccines might treat advanced ovarian cancer. Researchers are testing a mix of treatments, including cisplatin (a chemotherapy drug), celecoxib (a pain and inflammation reliever), and a special vaccine to see if they can enhance the body's ability to fight cancer. The trial targets individuals with advanced ovarian cancer who are beginning chemotherapy and are suitable candidates for surgery. Participants should not have active autoimmune diseases or allergies to the treatments involved. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative combination therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining cisplatin, chemokine modulatory treatments (CKM), and dendritic cell (DC) vaccines has been tested for safety in humans. Early studies indicate that the chemokine-targeting therapy is safe and generally well-tolerated. No major side effects were reported, and the treatment appeared to boost the immune system, which is promising for fighting cancer.

Cisplatin, a widely used chemotherapy drug, is known to cause side effects like nausea, kidney problems, and hearing loss. However, in controlled doses, it remains an important part of cancer treatment.

The DC vaccine uses a patient's own immune cells to enhance their ability to fight cancer. Previous trials have shown it to be non-toxic and aim to help the body better recognize and attack cancer cells.

Overall, past research suggests that the components of this trial are reasonably safe. Participants should still be aware of possible side effects and discuss any concerns with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine traditional chemotherapy with innovative immunotherapy approaches to tackle recurrent ovarian cancer. Unlike standard treatments, which often involve chemotherapy or targeted therapy alone, these experimental options incorporate vaccines and immune modulators like interferon (IFN) and rintatolimod. This combination aims to not only attack cancer cells directly but also boost the body's immune response to fight the cancer more effectively. Additionally, administering cisplatin directly into the peritoneal cavity (IP) and using intranodal vaccine injections represent unique delivery methods that could enhance the treatment's overall impact.

What evidence suggests that this trial's treatments could be effective for recurrent ovarian cancer?

Research has shown that combining the drug cisplatin with certain immune-boosting agents and vaccines may help treat ovarian cancer. In this trial, participants will be assigned to different treatment arms. One arm includes cisplatin combined with CKM, celecoxib, and the DC vaccine, while another arm includes cisplatin with celecoxib and the DC vaccine. One study found that a similar combination improved the overall response rate to 23%, compared to 17% with another drug used alone. These vaccines, which help the immune system fight cancer, have increased survival in some patients, especially those whose tumors are harder for the immune system to attack. The vaccines are generally safe and can lead to positive results, although this occurs in a smaller number of patients. Overall, this treatment combination could offer new hope for patients with advanced ovarian cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Robert P Edwards, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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 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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02432378

Study Details | NCT02432378 | Intensive Locoregional ... This study will evaluate the immunologic and potential clinical effectiveness of intensive locoregional sequential intraperitoneal (IP) cisplatin (IPC) with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9106847/

Phase I trial combining chemokine-targeting with loco ... We tested a novel intraperitoneal (IP) chemo-immunotherapy combination, to assess its tolerability and TME-modulatory impact in patients with recurrent EOC.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9406463/

Dendritic Cell Vaccines: A Promising Approach in the Fight ... We focus on the advancements in dendritic cell vaccination against ovarian cancer and highlight the key outcomes and pitfalls associated with currently used ...

4. researchgate.net researchgate.net/publication/357940735_Phase_I_Trial_Combining_Chemokine-Targeting_with_Loco-Regional_Chemoimmunotherapy_for_Recurrent_Platinum-Sensitive_Ovarian_Cancer_Shows_Induction_of_CXCR3_Ligands_and_Markers_of_Type_1_Immunity

Phase I Trial Combining Chemokine-Targeting with Loco ... Compared with nivolumab alone where the overall response rate (ORR) was 17%, cisplatin induction enhanced the ORR to 23% (95% CI: 5% to 53.8%) ...

5. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-11-149

A Phase I vaccine trial using dendritic cells pulsed with ... This study uses a novel autologous tumor vaccine developed with 4-day DCs pulsed with oxidized lysate to elicit antitumor response.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02151448?term=AREA%5BConditionSearch%5D(cancer)%20AND%20AREA%5BBasicSearch%5D(rintatolimod)&rank=8

αDC1 Vaccine + Chemokine Modulatory Regimen (CKM) ... This trial will evaluate the safety and effectiveness of autologous alpha-type-1 polarized dendritic cell (alpha-DC1) vaccines (patients' autologous alpha ...

7. trial.medpath.com trial.medpath.com/clinical-trial/a98da9ac5abb5a7d/nct02151448-phase-1-2-trial-alphaDC1-vaccines-adjuvant-therapy

αDC1 Vaccine + Chemokine Modulatory Regimen (CKM) as ... This trial will evaluate the safety and effectiveness of autologous alpha-type-1 polarized dendritic cell (alpha-DC1) vaccines (patients' autologous alpha ...

8. withpower.com withpower.com/trial/phase-2-carcinoma-ovarian-epithelial-8-2015-93852

Chemoimmunotherapy + Vaccines for Recurrent Ovarian ... This Phase 1 & 2 medical study run by Roswell Park Cancer Institute needs participants to evaluate whether Cisplatin will have tolerable side effects ...