~153 spots leftby Aug 2029

Heated Chemotherapy + Niraparib for Ovarian Cancer

(HOTT Trial)

Recruiting in Palo Alto (17 mi)
+50 other locations
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: GOG Foundation
Must not be taking: Antibiotics, Antidiabetics, Antihypertensives, others
Disqualifiers: Low-grade serous, Myelodysplastic, Pregnancy, others
Stay on Your Current Meds
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data

Trial Summary

What is the purpose of this trial?

Patients will be registered prior to, during or at the completion of neoadjuvant chemotherapy (Paclitaxel 175 mg/m2 IV over 3 hours and Carboplatin AUC 6 IV on Day 1 every 21 days for 3-4 cycles). Registered patients who progress during neoadjuvant chemotherapy will not be eligible for iCRS and will be removed from the study. Following completion of neoadjuvant chemotherapy, interval cytoreductive surgery (iCRS) will be performed in the usual fashion in both arms. Patients will be randomized at the time of iCRS (iCRS must achieve no gross residual disease or no disease \>1.0 cm in largest diameter) to receive HIPEC or no HIPEC. Patients randomized to HIPEC (Arm A) will receive a single dose of cisplatin (100mg/m2 IP over 90 minutes at 42 C) as HIPEC. After postoperative recovery patients will receive standard post-operative platinum-based combination chemotherapy. Patients randomized to surgery only (Arm B) will receive postoperative standard chemotherapy after recovery from surgery. Both groups will receive an additional 2-3 cycles of platinum-based combination chemotherapy per institutional standard (Paclitaxel 175 mg/m2 IV over 3 hours and Carboplatin AUC 6 IV on Day 1 every 21 days for 2-3 cycles) for a maximum total of 6 cycles of chemotherapy (neoadjuvant plus post-operative cycles) followed by niraparib individualized dosing until progression or 36 months (if no evidence of disease).

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, patients on stable doses of corticosteroids for at least 4 weeks prior to randomization can continue them, and those with controlled HIV can continue antiretroviral therapy. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Niraparib for ovarian cancer?

Niraparib has been shown to significantly extend the time patients live without their cancer getting worse (progression-free survival) in several studies, including a large phase III trial. It is effective for patients with ovarian cancer who have responded to platinum-based chemotherapy, regardless of specific genetic mutations.12345

Is the combination of heated chemotherapy and Niraparib safe for treating ovarian cancer?

Cisplatin, a component of heated chemotherapy, has been used in ovarian cancer treatment and can cause side effects like neuropathy (nerve damage) and blood-related issues such as neutropenia (low white blood cell count) and thrombocytopenia (low platelet count). Niraparib, another component, is generally well-tolerated but can also cause blood-related side effects. While these treatments have been used safely in many patients, they can have serious side effects, and their safety should be discussed with a healthcare provider.678910

How does the treatment of heated chemotherapy combined with niraparib differ from other ovarian cancer treatments?

This treatment is unique because it combines heated chemotherapy, which may enhance the effectiveness of the drugs by increasing their absorption, with niraparib, a PARP inhibitor that helps prevent cancer cells from repairing themselves. Niraparib is already used as a maintenance therapy for ovarian cancer, but combining it with heated chemotherapy could potentially offer a new approach to improve outcomes.2341112

Research Team

OZ

Oliver Zivanovic, MD

Principal Investigator

GOG Foundation

Eligibility Criteria

This trial is for patients with advanced high-grade serous or endometrioid ovarian, fallopian tube, or primary peritoneal cancer. They must have completed neoadjuvant chemotherapy and be candidates for surgery without large remaining tumors. Participants need normal organ function tests and a specific genetic test result before joining.

Inclusion Criteria

I am older than 18 years.
Patients must have a life expectancy > 3 months
I am fully active or restricted in physically strenuous activity but can do light work.
See 16 more

Exclusion Criteria

I have an active liver or biliary disease.
Patients with other uncontrolled, inter-current medical conditions
My ovarian cancer is of a specific type (low-grade serous, clear cell, mucinous, or non-epithelial).
See 20 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive Paclitaxel and Carboplatin every 21 days for 3-4 cycles

9-12 weeks

Interval Cytoreductive Surgery (iCRS)

Surgery performed to achieve no gross residual disease, followed by randomization to HIPEC or no HIPEC

1 week

Post-operative Chemotherapy

Participants receive additional 2-3 cycles of platinum-based combination chemotherapy

6-9 weeks

Niraparib Maintenance

Participants receive niraparib individualized dosing until progression or 36 months

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 8 years

Treatment Details

Interventions

  • Cisplatin (Alkylating agents)
  • Niraparib (PARP Inhibitor)
Trial OverviewThe study compares two approaches after initial chemo: one group receives heated intraperitoneal chemotherapy (HIPEC) with cisplatin during surgery, while the other does not. Both groups get more chemo post-surgery and then niraparib until disease progression or up to 36 months.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: HIPECExperimental Treatment1 Intervention
Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Cisplatin 100 mg/m2 IP over 90 minutes at 42 degrees C
Group II: No HIPECActive Control1 Intervention
No treatment

Find a Clinic Near You

Research Locations NearbySelect from list below to view details:
UH Geauga Medical CenterChardon, OH
St. John Medical CenterWestlake, OH
Yale University School of MedicineNew Haven, CT
University Hospitals Cleveland Medical CenterCleveland, OH
More Trial Locations
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Who Is Running the Clinical Trial?

GOG Foundation

Lead Sponsor

Trials
48
Patients Recruited
18,500+

GlaxoSmithKline

Industry Sponsor

Trials
4834
Patients Recruited
8,389,000+
Headquarters
London, UK
Known For
Vaccines & Medicines
Top Products
**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Findings from Research

Niraparib for the treatment of ovarian cancer.Kanjanapan, Y., Lheureux, S., Oza, AM.[2018]
Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients.van Andel, L., Rosing, H., Zhang, Z., et al.[2019]
Niraparib: A Review in First-Line Maintenance Therapy in Advanced Ovarian Cancer.Lee, A.[2022]
Niraparib: A Review in Ovarian Cancer.Heo, YA., Duggan, ST.[2019]
Niraparib as maintenance therapy in a patient with ovarian cancer and brain metastases.Gray, S., Khor, XY., Yiannakis, D.[2021]
In a study involving 25 ovarian cancer patients who had previously been treated with platinum-based therapies, the combination of oxaliplatin and cisplatin showed an overall objective response rate of 40%, with 8% achieving complete responses and 32% partial responses.
The main side effect of this treatment was cumulative sensory peripheral neuropathy, which was severe in some cases but reversible after stopping the treatment, highlighting the need for careful monitoring of patients during therapy.
Oxaliplatin/cisplatin (L-OHP/CDDP) combination in heavily pretreated ovarian cancer.Soulié, P., Bensmaïne, A., Garrino, C., et al.[2019]
Intraperitoneal carboplatin in the treatment of minimal residual ovarian cancer.Pfeiffer, P., Bennedbaek, O., Bertelsen, K.[2019]
The combination of paclitaxel and carboplatin showed an overall response rate of 42% in 73 patients with advanced ovarian cancer who had previously undergone platinum-based chemotherapy, indicating its efficacy as a treatment option.
While myelosuppression was the most common severe side effect, with significant rates of neutropenia, the therapy was generally well-tolerated, with only one case of febrile neutropenia and manageable levels of other toxicities.
Efficacy and safety of the paclitaxel and carboplatin combination in patients with previously treated advanced ovarian carcinoma. A multicenter GINECO (Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens) phase II study.Guastalla, JP., Pujade-Lauraine, E., Weber, B., et al.[2020]
Intraperitoneal cisplatin and intravenous paclitaxel in the treatment of epithelial ovarian cancer patients with a positive second look.Makhija, S., Sabbatini, P., Aghajanian, C., et al.[2015]
Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies.Tai, YH., Tai, YJ., Hsu, HC., et al.[2020]
[Évolution des traitements adjuvants des cancers de l'ovaire].Pautier, P.[2022]
Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial.Mirza, MR., Benigno, B., Dørum, A., et al.[2021]

References

Niraparib for the treatment of ovarian cancer. [2018]
Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. [2019]
Niraparib: A Review in First-Line Maintenance Therapy in Advanced Ovarian Cancer. [2022]
Niraparib: A Review in Ovarian Cancer. [2019]
Niraparib as maintenance therapy in a patient with ovarian cancer and brain metastases. [2021]
Oxaliplatin/cisplatin (L-OHP/CDDP) combination in heavily pretreated ovarian cancer. [2019]
Intraperitoneal carboplatin in the treatment of minimal residual ovarian cancer. [2019]
Efficacy and safety of the paclitaxel and carboplatin combination in patients with previously treated advanced ovarian carcinoma. A multicenter GINECO (Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens) phase II study. [2020]
Intraperitoneal cisplatin and intravenous paclitaxel in the treatment of epithelial ovarian cancer patients with a positive second look. [2015]
Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies. [2020]
[Évolution des traitements adjuvants des cancers de l'ovaire]. [2022]
12.United Statespubmed.ncbi.nlm.nih.gov
Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial. [2021]