Nivolumab + Chemotherapy for Head and Neck Cancer
(DEPEND Trial)
Recruiting in Palo Alto (17 mi)
Overseen byEverett Vokes, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Chicago
Must not be taking: Steroids, Immunosuppressants
Disqualifiers: Metastatic disease, Immunodeficiency, Active infection, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This study is looking to see if nivolumab, an immunotherapy drug, given with carboplatin and paclitaxel (2 chemotherapy agents) during induction therapy in advanced stage HPV negative patients can significantly shrink the subject's cancer.
Do I need to stop my current medications to join the trial?
The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to stop these at least 7 days before starting the trial treatment.
What data supports the effectiveness of the drug combination Nivolumab, Carboplatin, and Paclitaxel for head and neck cancer?
Research shows that using paclitaxel and carboplatin together can help treat advanced head and neck cancer, potentially improving survival and preserving organs. This suggests that adding Nivolumab, which is known to boost the immune system, might further enhance treatment effectiveness.
12345Is the combination of Nivolumab, Carboplatin, and Paclitaxel safe for treating head and neck cancer?
The combination of Carboplatin and Paclitaxel has been studied in head and neck cancer, showing tolerable safety with some side effects like neutropenia (low white blood cell count) and neurotoxicity (nerve damage). No treatment-related deaths were reported in these studies, indicating a generally acceptable safety profile.
16789How is the drug combination of Nivolumab, Carboplatin, and Paclitaxel unique for head and neck cancer?
This treatment is unique because it combines Nivolumab, an immunotherapy drug that helps the immune system attack cancer cells, with chemotherapy drugs Carboplatin and Paclitaxel, which kill cancer cells directly. Nivolumab has shown to improve survival in patients with head and neck cancer who have not responded to platinum-based chemotherapy, offering a new option beyond traditional chemotherapy alone.
310111213Eligibility Criteria
Adults with advanced stage IV HPV-negative head and neck cancer, who haven't had chemotherapy or radiation for this condition. They must have a good performance status, normal organ function, no history of severe allergies to the drugs used in the trial, not be pregnant or breastfeeding, and agree to use contraception.Inclusion Criteria
Total bilirubin ≤ 1.5 mg/dL
Absolute neutrophil count ≥ 1,500
My organs are functioning normally.
+21 more
Exclusion Criteria
My cancer has spread to distant parts of my body.
The origin of my cancer is unknown.
I have not taken high-dose steroids or immunosuppressants in the last 7 days.
+12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Induction Therapy
Participants receive induction therapy with nivolumab, carboplatin, and paclitaxel to assess tumor response
2-3 weeks
Multiple visits for treatment and monitoring
Chemoradiation
Participants receive risk-adapted chemoradiotherapy based on response to induction therapy
24 months
Regular visits for treatment and monitoring
Follow-up
Participants are monitored for safety, effectiveness, and quality of life after treatment
24 months
Periodic visits for assessments
Participant Groups
The study is testing if nivolumab combined with carboplatin and paclitaxel can shrink cancers significantly in patients with advanced HPV-negative head and neck cancer before they receive other treatments like surgery or more chemo.
2Treatment groups
Experimental Treatment
Group I: ARM 2Experimental Treatment6 Interventions
Radiation therapy with chemotherapy
Group II: ARM 1Experimental Treatment3 Interventions
Induction Therapy
Carboplatin is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Paraplatin for:
- Ovarian cancer
- Testicular cancer
- Lung cancer
- Head and neck cancer
- Brain cancer
🇪🇺 Approved in European Union as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
🇨🇦 Approved in Canada as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
- Testicular cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University Of Chicago Medicine Comprehensive Cancer CenterChicago, IL
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Who Is Running the Clinical Trial?
University of ChicagoLead Sponsor
References
Paclitaxel and carboplatin in head and neck cancer. [2015]Surgery and radiation for advanced head and neck cancer are debilitating and associated with poor survival. If outpatient preoperative chemotherapy could be used such that smaller surgical resections are needed, organs might be preserved and patients' quality of life enhanced. Accordingly, we are conducting a phase I trial of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin in previously untreated patients with advanced head and neck cancer. Study goals include identifying the maximum tolerated paclitaxel dose, evaluating response, and enhancing organ preservation. Newly diagnosed patients with stage III/IV head and neck cancer, measurable disease, and Zubrod performance status
Induction paclitaxel and carboplatin for patients with head and neck carcinoma. Analysis of 62 patients treated between 1994 an 1999. [2015]After standard therapy for advanced head and neck carcinoma, 5-year survival rate is less than 50%. Our purpose was to develop a new treatment for advanced head and neck carcinoma by using preoperative chemotherapy. Long term efficacy and toxicity of induction paclitaxel and carboplatin is reported here.
Phase II trial of a paclitaxel-carboplatin combination in recurrent squamous cell carcinoma of the head and neck. [2017]Twenty-seven patients with recurrent squamous cell carcinoma of the head and neck were entered in a multicenter study to determine the efficacy of the paclitaxel-carboplatin association.
Analysis of cell-cycle checkpoint pathways in head and neck cancer cell lines: implications for therapeutic strategies. [2019]To determine the mechanism of action of paclitaxel (Taxol) and carboplatin in cell lines of head and neck squamous cell carcinoma (HNSCC).
Weekly paclitaxel in patients with recurrent or metastatic head and neck cancer. [2015]To evaluate the efficacy and safety of weekly paclitaxel in patients with recurrent or metastatic head and neck cancer (HNC) by combined analysis of early and late phase II trials.
Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. [2021]Background and Objectives: In recent years, the effectiveness of chemotherapy after immune checkpoint inhibitor administration has attracted attention in various cancers, including head and neck cancers. However, individual assessments of the administered chemotherapy regimens are insufficient. This study aimed to evaluate the efficacy and safety of chemotherapy after immune checkpoint inhibitor administration in recurrent metastatic head and neck cancer by focusing on a single regimen. Materials and Methods: We retrospectively reviewed clinical and radiological data from the medical records of 18 patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who received systemic chemotherapy with weekly cetuximab and paclitaxel (Cmab + PTX) after progression following immune checkpoint inhibitor (ICI) therapy. The objective response rate (ORR) and disease control rate (DCR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Adverse events (AEs) were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: In all patients, the ORR, DCR, median PFS, and median OS were 44.4%, 72.2%, 3.8 months, and 9.6 months, respectively. Regarding AEs, three patients developed grade 3 neutropenia. Grade 3 anemia, paronychia, asthenia, and peripheral neuropathy were observed in one patient each. There were no treatment-related deaths. Conclusions: Cmab + PTX was shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after ICI therapy. Further research is needed to establish optimal treatment sequences and drug combinations for recurrent R/M HNSCC.
Survival outcomes in patients with oropharyngeal cancer treated with carboplatin/paclitaxel and concurrent radiotherapy. [2018]A commonly employed treatment for advanced staged oropharyngeal squamous cell carcinoma (OPSCC) is concurrent radiation and chemotherapy with cisplatin as the gold standard. Carboplatin is reported to have the same radiopotentiation properties and a superior side effect profile; however, its use in head and neck cancer has been limited due to the paucity of data and reported hematologic side effects. In this study, we describe our institution's experience with carboplatin, paclitaxel and radiation in the treatment of oropharyngeal squamous cell carcinoma over a 10 year period.
Phase I/II study of paclitaxel/cisplatin as first-line therapy for locally advanced head and neck cancer. [2015]A phase I/II study was conducted to determine the response rate and the toxicity of escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus cisplatin with granulocyte colony-stimulating factor support in patients with untreated advanced head and neck carcinoma. Twenty-eight patients with locally advanced inoperable squamous cell head and neck carcinoma were included. Median age was 51 years. Karnofsky performance status was > or =90% in all patients. Primary tumor sites were oropharynx, hypopharynx, larynx, oral cavity, parotid gland, nasal cavity, and unknown primary. We observed 13 complete responses, eight partial responses, four patients with stable disease, and two patients with progressive disease for an overall response rate of 78%. Toxicity was paresthesia grade 1/2 in 27 patients, and myalgias were grade 1/2 in 23 patients and grade 3 in four patients. One patient died 5 days after the first cycle due to acute renal failure, respiratory distress, and pancytopenia. No dose-limiting hematologic toxicity has been observed, and intrapatient escalations were performed in all patients when planned. Calculated dose intensity for the two drugs was 100% in all evaluable patients. The combination of escalating doses of paclitaxel 175 to 300 mg/m2 and cisplatin 75 mg/m2 was active in untreated head and neck carcinoma, with an overall response rate of 78%. No dose-limiting toxicity has been encountered at paclitaxel doses up to 300 mg/m2 given with granulocyte colony-stimulating factor.
Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers. [2019]A phase II study was conducted to evaluate the activity of paclitaxel and carboplatin in advanced head and neck cancer. Twenty-four patients with measurable locoregional squamous cell carcinoma and metastatic disease were entered. All had been heavily pretreated with radiotherapy, surgery and chemotherapy and were at second recurrence or disease progression when they entered the trial. Patients received Paclitaxel 200 mg/m2 with carboplatin 7 AUC once every 3 weeks with premedication with dexamethasone and diphenyldramine and ranitidine. Twenty-three patients were evaluable for response. Four patients (17%) achieved a complete response and 5 (22%) a partial response for an overall response rate of 39%. Duration of response was 3-9 months. Toxicity was tolerable. Four patients showed Grade III (WHO) and 6 Grade II neutropenia. Nineteen (79%) of patients who received more than two courses of chemotherapy presented neurotoxicity. The combination of paclitaxel and carboplatin was effective in heavily pretreated patients with squamous cell carcinoma of the head and neck.
Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. [2022]Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition.
Successful Treatment of Refractory Squamous Cell Cancer of the Head and Neck with Nivolumab and Ipilimumab. [2022]Treatment options for patients with platinum-refractory, recurrent, metastatic head and neck squamous cell carcinoma (HNSCC) are limited, and prognosis is poor. Nivolumab (Opdivo) has been approved by the US Food and Drug Administration (FDA) for the treatment of patients with recurrent or metastatic HNSCC who have disease progression on or after platinum-based therapy. Recently, in patients with metastatic malignant melanoma a significant improvement of outcome and response was achieved with the combination of ipilimumab (CTLA4 antibody) and the programmed death (PD)-1 inhibitor nivolumab compared with monotherapy. Based on these results, the combination of nivolumab and ipilimumab has been approved by the FDA for the treatment of patients with unresectable or metastatic melanoma. So far, there have been no data concerning the combination of nivolumab and ipilimumab in squamous cell head and neck cancer. We here present the case of a 46-year-old male with refractory squamous cell head and neck cancer, who was successfully treated with the PD-1 inhibitor nivolumab in combination with the anti-CTLA4 antibody ipilimumab.
Nivolumab Doubles Survival for Patients with HNSCC. [2019]In patients with head and neck squamous cell carcinoma refractory to platinum-based chemotherapy, those treated with nivolumab had a 30% reduction in the risk of death compared with those assigned to receive one of three single-agent chemotherapies, according to a recent phase III trial. In addition, 1-year survival among nivolumab recipients was double that of those who received a chemotherapeutic, the current standard of care.
Chemotherapy for recurrent/metastatic head and neck cancers. [2019]Chemotherapy is the only option of treatment for most patients presenting with a recurrent and/or metastatic head and neck squamous cell carcinoma. The triple association of cisplatin, 5-fluorouracile, and cetuximab is still the current standard for fit patients. Other schemes are currently being compared with this protocol in ongoing trials and the association of cisplatin, docetaxel, and cetuximab appears to be the most efficient. The human papilloma virus is very likely a favorable prognostic factor. Immunotherapy with nivolumab or pembrolizumab is now a new standard of treatment in second line after yielding an improvement in overall survival, but predictive markers of efficacy are needed to refine the selection of patients. The combination of paclitaxel and buparlisib appears to be promising.