Heated Chemotherapy + Niraparib for Ovarian Cancer (HOTT Trial)
Palo Alto (17 mi)Age: 18+
Sex: Female
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: GOG Foundation
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).
Is the drug Niraparib a promising treatment for ovarian cancer?Yes, Niraparib is a promising drug for ovarian cancer. It helps extend the time patients live without the cancer getting worse after chemotherapy. It works for many patients, even if they don't have specific genetic mutations. It is also considered safe with manageable side effects.68101112
What data supports the idea that Heated Chemotherapy + Niraparib for Ovarian Cancer is an effective treatment?The available research shows that Niraparib, when used as a maintenance treatment for ovarian cancer, helps patients live longer without the cancer getting worse. In several studies, patients who took Niraparib after responding to chemotherapy had a longer time before their cancer progressed compared to those who did not take the drug. This was true for patients with specific genetic mutations and those without. Niraparib is also considered safe to use, with side effects that can be managed by adjusting the dose. Overall, Niraparib is a promising option for maintaining health in ovarian cancer patients after initial treatment.568911
What safety data is available for heated chemotherapy with cisplatin and niraparib in ovarian cancer treatment?The safety data for cisplatin, a component of the treatment, indicates that it can cause cumulative sensory peripheral neuropathy, neutropenia, and thrombopenia, with severe cases leading to treatment-related death. Intraperitoneal administration of cisplatin has been associated with mild nausea and vomiting. Hypersensitivity reactions to carboplatin, a related platinum compound, are more common with higher doses and prolonged treatment. Niraparib, another component, is not directly mentioned in the provided studies, but it is known to have its own safety profile, including potential hematological toxicities. Overall, the combination of platinum-based chemotherapy with other agents like paclitaxel has shown varying toxicity profiles, with some combinations being better tolerated than others.12347
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop taking your current medications. However, patients on corticosteroids can continue if their dose is stable for at least 4 weeks before randomization. If you are on full-dose oral anticoagulation, your INR should be in-range. It's best to discuss your specific medications with the trial team.
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.
I am fully active or restricted in physically strenuous activity but can do light work.
My blood tests show enough hemoglobin, neutrophils, and platelets.
My nerve damage does not severely affect my daily activities.
I have no visible cancer larger than 1 cm after initial surgery.
My liver tests are within the required limits.
I have advanced ovarian, fallopian tube, or peritoneal cancer and am a candidate for surgery after chemotherapy.
My scans show no signs of cancer outside my abdomen after treatment.
My kidney function is normal, with creatinine ≤ 1.3mg/dl and clearance ≥ 30 mL/min.
Exclusion Criteria
I have an active liver or biliary disease.
My ovarian cancer is of a specific type (low-grade serous, clear cell, mucinous, or non-epithelial).
I have a history of Myelodysplastic Syndrome or Acute Myeloid Leukemia.
I have uncontrolled diabetes or a kidney condition.
I have hearing loss before starting the trial.
I have a serious heart condition.
My cancer progressed during initial treatment, as shown in recent scans.
I have not had a severe infection needing IV antibiotics in the last 2 weeks.
My cancer has spread to my brain or spinal cord.
I have had Reversible Encephalopathy Syndrome in the past.
I have active hepatitis B.
I have not received a live vaccine in the last 30 days.
I've had radiation on more than 20% of my bone marrow within the last 2 weeks.
My stage IV cancer has not fully responded to treatment and cannot be surgically removed.
I have significant stomach or intestine issues.
Treatment Details
The 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.
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 FoundationLead Sponsor
GlaxoSmithKlineIndustry Sponsor
References
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.
Oxaliplatin/cisplatin (L-OHP/CDDP) combination in heavily pretreated ovarian cancer. [2019]The aim of this study was to evaluate the toxicity and the activity of two non-cross-resistant platinum compounds: oxaliplatin (L-OHP) and cisplatin (CDDP) in platinum pretreated ovarian cancer patients. Chemotherapy consisted of L-OHP and CDDP given sequentially as 2 h infusions on day 1 at their standard recommended dose (130 mg/m2 for oxaliplatin, 100 mg/m2 for cisplatin) every 3 weeks. Dose reductions (20-35%) were planned according to baseline haematological and renal status, but the dose ratio between L-OHP and CDDP was always maintained at 1.3. Cycles were repeated until progression or treatment limiting toxicities. From September 1992 to November 1994, 25 patients with pretreated ovarian cancer entered this salvage programme. They had received a median number of three previous chemotherapy lines (1-7), one at least platinum based. Previously cisplatin had been given to 22 patients at a median total dose of 600 mg/m2 (170-1175), while 18 had received carboplatin to a median total dose of 1135 mg/m2 (200-2450). 9 patients had also received and were resistant to taxanes (paclitaxel, 6 patients, docetaxel, 3 patients), while the rest were considered ineligible for simultaneously ongoing single-agent taxane phase II trials. 13 and 12 patients, respectively, were considered to have platinum refractory and potentially sensitive disease, according to Markman's criteria. 77 cycles of L-OHP/CDDP were given, with a median of three cycles/patient (range 1-6) and were evaluable for toxicity. The limiting toxicity of the L-OHP/CDDP combination was a cumulative, sensory peripheral neuropathy, severe (> or = grade 3 CTC) after more than three cycles, but reversible within a few months of its discontinuation. Grade 3-4 (WHO scale) neutropenia and thrombopenia were seen in 35-40% of cycles, with one neutropenic treatment-related death (septic shock). 22 patients with measurable/evaluable disease were assessable for antitumoral activity. Two complete responses (CR) (8%) (one proven histologically at laparotomy (pCR)) and 8 partial responses (PR) (32%) for an overall objective response rate (ORR) of 40% (95% CI, 21-61%) (intent to treat). The median duration of response was 4 months. Seven responses were seen among 12 potentially platinum-sensitive tumours (58%, CI 95% 28-85%), while 3/13 platinum refractory patients (23%, CI 95% 5-54%) had an objective response. These encouraging results are the basis for new first- and second-line combination treatment programmes in ovarian carcinoma.
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]Platinum compounds are the most active drugs in ovarian cancer treatment; cisplatin and carboplatin demonstrated similar efficacies but different toxicity profiles. Paclitaxel combined with cisplatin as first-line treatment improved overall survival when compared to a cisplatin-cyclophosphamide combination, but generated higher rates of neutropenia, febrile neutropenia and neurotoxicity. The paclitaxel-carboplatin combination may be better tolerated than cisplatin-paclitaxel.
Intraperitoneal cisplatin and intravenous paclitaxel in the treatment of epithelial ovarian cancer patients with a positive second look. [2015]The aim of this study was to review the role and safety of intraperitoneal (IP) cisplatin and intravenous (IV) paclitaxel in platinum-sensitive epithelial ovarian cancer patients who were found to have small-volume disease (
Niraparib for the treatment of ovarian cancer. [2018]Label="INTRODUCTION" NlmCategory="BACKGROUND">Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are being developed in maintenance and recurrence treatment settings in ovarian cancer. They inhibit single-stranded DNA repair, inducing synthetic lethality in cells with underlying homologous recombination deficiency (HRD). Marked responses are seen in ovarian cancers with breast cancer gene 1 (BRCA1) or 2 (BRCA2) mutation, although up to 50% of high-grade serous ovarian cancers (HGSOC) have HRD may also benefit. Areas covered: This review focuses on niraparib (oral PARP I and II inhibitor), its clinical testing in ovarian cancer, including the Myriad MyChoice HRD test as a potential companion diagnostic. Future directions plus ongoing trials, including novel combinations are highlighted. Expert opinion: There is now level 1 evidence of efficacy from the first randomized placebo-controlled phase III trial using niraparib maintenance in women with platinum-sensitive recurrent HGSOC with complete or partial response post platinum-based chemotherapy. Niraparib improved progression free survival over placebo in all groups of women. The benefit was greatest in patients with germline BRCA1/2 mutation, followed by HRD positive tumors; however, absence of either does not exclude the possibility of benefit from niraparib maintenance. Additional studies are underway with niraparib in the first line maintenance, and 4th/5th line recurrence treatment settings.
Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. [2019]Niraparib (Zejula™) is a poly(ADP-ribose) polymerase inhibitor recently approved by the US Food and Drug Administration for the maintenance treatment of patients with recurrent platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. The pivotal phase III clinical trial has shown improved progression-free survival in patients receiving niraparib compared with those receiving placebo.
Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies. [2020]We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease (P < 0.001, Kruskal-Wallis test), serous and mixed histological types (P = 0.003, Kruskal-Wallis test), malignant ascites (P = 0.009, chi-square test), and history of other drug allergy (P < 0.001, chi-square test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P < 0.001, independent sample t-test) and dose (6,816 vs. 3,844 mg, P < 0.001, independent sample t-test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications.
Niraparib: A Review in Ovarian Cancer. [2019]Niraparib (Zejula®), a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for the maintenance treatment of recurrent, epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in complete or partial response to platinum-based chemotherapy. Approval was based on the results of the randomized, double-blind, placebo-controlled phase III NOVA trial. In NOVA, niraparib significantly prolonged progression-free survival (primary endpoint), chemotherapy-free interval and time to first subsequent therapy compared with placebo in patients with recurrent, platinum-sensitive, high grade serous ovarian, fallopian tube or primary peritoneal cancer. The beneficial effects of niraparib were consistent regardless of BRCA mutation or homologous recombination deficiency (HRD) status. Niraparib had a manageable tolerability profile, with the majority of grade 3 or 4 adverse events being haematologic abnormalities (e.g. thrombocytopenia, anaemia, neutropenia). Adverse events were generally well managed with dose interruption or modification of niraparib. Current evidence suggests that niraparib is an effective new option with a manageable tolerability profile for the maintenance treatment of recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer in adults, with or without BRCA1/2 mutation or HRD.
Niraparib as maintenance therapy in a patient with ovarian cancer and brain metastases. [2021]Ovarian cancer is the second the most common gynaecological malignancy in developed countries. 70% of patients relapse in the first 3 years following debulking surgery and first-line chemotherapy. Niraparib is a poly adenosine diphosphate ribose polymerase inhibitor which uses the concept of synthetic lethality in the presence of a mutation in the breast cancer susceptibility gene (BRCA), and is now recommended as maintenance treatment in patients with platinum-sensitive relapse of ovarian cancer. It has been shown to increase progression-free survival. We present a case of a 68-year-old woman with brain metastases from high-grade serous ovarian cancer who has remained free of disease progression for longer than 17 months with niraparib use as maintenance treatment after second-line chemotherapy.
Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial. [2021]Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved for use in heavily pretreated patients and as maintenance treatment in patients with newly-diagnosed or recurrent ovarian cancer following a response to platinum-based chemotherapy. We present long-term safety data for niraparib from the ENGOT-OV16/NOVA trial.
Niraparib: A Review in First-Line Maintenance Therapy in Advanced Ovarian Cancer. [2022]Niraparib (Zejula™) is a PARP inhibitor which is approved for maintenance therapy in adults with advanced ovarian cancer in complete or partial response to platinum-based chemotherapy. In a placebo-controlled phase III trial in patients with newly diagnosed advanced ovarian cancer, niraparib significantly extended progression free survival in two predefined populations, namely a patient population with altered homologous-recombination DNA repair pathways [i.e. homologous-recombination deficiency positive (HRd)] and the overall trial population. A prespecified exploratory subgroup analysis indicated that niraparib was also efficacious in patients who were homologous recombination deficiency negative or homologous recombination proficient (HRp). Niraparib has a manageable tolerability profile with myelosuppression as the main safety concern. Haematological reactions were managed with monitoring and dose reduction or interruption. A weight- and platelet count-based individualised dosage regimen introduced during the trial (and subsequently approved) appeared to improve haematological tolerability. Niraparib is a useful option for first-line maintenance therapy for advanced ovarian cancer in adults who responded to platinum-based chemotherapy, regardless of homologous-recombination deficiency status and is a promising option for HRp patients, for whom maintenance treatment options are limited.
[Évolution des traitements adjuvants des cancers de l'ovaire]. [2022]EVOLUTION IN ADJUVANT TREATMENT OF OVARIAN CARCINOMA High grade cancer of the ovary is a poor prognosis disease most often diagnosed at an advanced stage. Main prognostic factors include stage of disease, possibility of complete surgery and chemosensitivity. New maintenance targeted therapy deeply changed the prognosis of some ovarian cancers. In early stages, adjuvant treatment after surgery remains based on a platinum-based association for 6 cycles. In initially inoperable advanced stages, neoadjuvant chemotherapy must be discussed on a case-by-case basis during a multidisciplinary meeting. Standard of care remains first-line chemotherapy -with the 3 weekly association carboplatin- paclitaxel-, with or without bevacizumab after surgery. Poly-(ADP-ribose) polymerase inhibitors (PARPi) are indicated as maintenance treatment from the first line of advanced forms (FIGO stages III and IV) with BRCA1 or BRCA2 mutation following partial or complete response to chemotherapy (olaparib ou niraparib), when there is no indication for bevacizumab; they are also indicated as maintenance treatment with olaparib associated to bevacizumab in patients whose HRD test (homologous recombination deficiency : DNA repair defect by homologous recombination) is positive (with or without BRCA mutation) and have an indication for bevacizumab. In case of contraindication or no indication for bevacizumab, niraparib can also be used alone for 3 years after response to chemotherapy, whatever the HR status.