Participants in this study have a type of cancer called squamous cell carcinoma of the head and neck (SCCHN). Their SCCHN has spread around the area where the cancer first started. This is called locally-advanced SCCHN. These participants are eligible for surgery.
Previous research with a similar therapy regimen resulted in high rates of cancer shrinkage, high rates of avoiding radiation and its side effects, high cure rate and good quality of life. Radiation can be very toxic. The purpose on this study is to try to avoid radiation. If the participants are not on this study they would be receiving radiation as it is standard treatment of their cancer. In the last study with a similar regimen, about a third of cancers had a pathologic complete response with the first part of the study. This means that the chemotherapy had killed the cancer. The investigators are trying to improve the regimen further with a goal of increasing this rate of complete response to the first part of therapy. The investigators also hope that by improving results in the first part, that more people will be cured and that long term quality of life (especially speech and swallowing) will be improved, both compared to standard therapies and to the last study. Doctors do not know how this therapy will effect the participants. There is no guarantee that this study will benefit the participants.
The prior study used a combination of chemotherapy consisting of carboplatin, paclitaxel and a third targeted anti-cancer drug. In this study the investigators are testing the combination of carboplatin, nano-albumin bound paclitaxel and durvalumab. Nano-albumin bound paclitaxel has been shown to be more active against other types of squamous cancers than regular paclitaxel. It is FDA approved for squamous lung cancer, but experimental for head and neck cancer. Durvalumab is an experimental drug that uses the body's own immune system to fight the cancer. Doctors hope that combining Durvalumab with 2 chemotherapy drugs will be effective in treating SCCHN. Durvalumab on its own has been studied in patients with SCCHN and initial results have shown that some subjects' cancer has responded to it.
The purpose of this study is to test a combination of chemotherapy to hopefully both increase the number of subjects that respond to therapy while also decreasing the number of side effects that subjects experience.
Condition or disease | Intervention/treatment | Phase |
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Carcinoma, Squamous Cell Oral Cancer Oropharynx Cancer Larynx Cancer Lip Cancer Esophageal Cancer | Drug: Durvalumab Drug: Carboplatin Drug: Nab-paclitaxel Drug: Cisplatin Procedure: Surgical resection Radiation: IMRT | Phase 2 |
STUDY OBJECTIVES
Primary Objective:
Estimate the pathologic complete response rate (pCRR) after induction chemotherapy with carboplatin, nab-paclitaxel, and durvalumab in previously untreated stage III and IV SCCHN amenable to surgical resection
Secondary Objectives:
Translational/Exploratory Objectives:
PROCEDURES This is a single-arm, nonrandomized phase II trial consisting of 3 parts. After informed consent and screening, pre-induction, risk levels will be assessed clinically, by a combination of physical exam and imaging.
Part 1: All patients will then receive 6 weeks of induction chemotherapy in Part 1 comprised of weekly cycles of carboplatin and nab-paclitaxel for 6 cycles in combination with durvalumab administered once every two weeks for 5 cycles (Day 1 of the weeks 1, 3, 5, 7, and 9).
Part 2: Within a 1-4 the week window post induction, tumor imaging will be followed by surgical resection.
Part 3: After surgery, patients will be stratified into one of 3 risk categories based on their disease pathology, assigned a treatment group based on their risk. Low risk patients with receive durvalumab once every two weeks for 3 cycles, while medium risk or high risks groups will receive concurrent chemoradiation therapy followed by durvalumab once every two weeks for 3 cycles.
Follow up After completion of study therapy (which will vary by study arm) patients will be evaluated every three months during follow up for progression over a period of 18 months. Each follow up visit will include physical examination, CT or MRI imaging of the neck. Chest imaging will be obtained (or not) as indicated by standard of care. After the first 18 months, patients will be followed-up per standard of care, with documentation in the case report form (CRF) limited to progression and survival noted at their standard of care visits. If a patient should move away or otherwise be lost to in-person follow up but is amenable to telephone follow up, this will be permitted during the standard of care follow up period.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 39 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Multimodality Therapy With Induction Carboplatin/Nab-Paclitaxel/Durvalumab Followed by Surgical Resection and Risk-adapted Adjuvant Therapy for the Treatment of Locally-Advanced and Surgically Resectable Squamous Cell Carcinoma of the Head and Neck |
Actual Study Start Date : | December 19, 2017 |
Estimated Primary Completion Date : | September 1, 2021 |
Estimated Study Completion Date : | September 1, 2026 |
Arm | Intervention/treatment |
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Experimental: Low Risk
Part 1- Patients receive 6 weeks of induction chemotherapy comprised of weekly cycles of carboplatin dosed to an Area Under the Curve (AUC2) and nab-paclitaxel 100 mg/m2 X 6 cycles in combination with durvalumab 750 mg administered once every two weeks for 5 cycles (D1 of weeks 1, 3, 5, 7, and 9). Part 2- Within a 2-6 week window post induction, tumor imaging will be followed by surgical resection. Part 3- patients receive adjuvant durvalumab (750 mg) once every two weeks x 3 cycles |
Drug: Durvalumab
Subjects will receive durvalumab, 750 mg every 2 weeks by IV infusion over approximately 1 hour (± 5 minutes).
Other Name: MEDI4736
Drug: Carboplatin Carboplatin is commercially available and approved by the US FDA for use in patients with ovarian cancer.
Other Name: Paraplatin
Drug: Nab-paclitaxel Nab-paclitaxel is commercially available and approved by the US Food and Drug Administration (FDA) for use in patients with metastatic breast cancer, metastatic pancreatic cancer, and for the treatment of locally advanced or metastatic NSCLC.
Other Name: Abraxane
Procedure: Surgical resection Surgical therapy will be at the discretion of the treating surgeon per standard of care.
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Experimental: Medium Risk
Part 1- Patients receive 6 weeks of induction chemotherapy comprised of weekly cycles of carboplatin dosed to an Area Under the Curve (AUC2) and nab-paclitaxel 100 mg/m2 X 6 cycles in combination with durvalumab 750 mg administered once every two weeks for 5 cycles (D1 of weeks 1, 3, 5, 7, and 9). Part 2- Within a 2-6 week window post induction, tumor imaging will be followed by surgical resection. Part 3- patients receive ipsilateral involved field radiation concurrent with weekly cisplatin 30mg/m2. Once chemoradiotherapy is complete these patients will receive durvalumab 750 mg every two weeks for 3 cycles. |
Drug: Durvalumab
Subjects will receive durvalumab, 750 mg every 2 weeks by IV infusion over approximately 1 hour (± 5 minutes).
Other Name: MEDI4736
Drug: Carboplatin Carboplatin is commercially available and approved by the US FDA for use in patients with ovarian cancer.
Other Name: Paraplatin
Drug: Nab-paclitaxel Nab-paclitaxel is commercially available and approved by the US Food and Drug Administration (FDA) for use in patients with metastatic breast cancer, metastatic pancreatic cancer, and for the treatment of locally advanced or metastatic NSCLC.
Other Name: Abraxane
Drug: Cisplatin Cisplatin is commercially available and approved by the US Food and Drug Administration (FDA) for the treatment of advanced bladder, ovarian and testicular cancer. It has been widely studied in a variety of solid tumor types.
Procedure: Surgical resection Surgical therapy will be at the discretion of the treating surgeon per standard of care.
Radiation: IMRT "involved field radiation" will refer to areas demonstrated to harbor disease on pathology, and not elective areas
Other Name: Intensity-modulated radiation therapy
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Experimental: High Risk
Part 1- Patients receive 6 weeks of induction chemotherapy comprised of weekly cycles of carboplatin dosed to an Area Under the Curve (AUC2) and nab-paclitaxel 100 mg/m2 X 6 cycles in combination with durvalumab 750 mg administered once every two weeks for 5 cycles (D1 of weeks 1, 3, 5, 7, and 9). Part 2- Within a 2-6 week window post induction, tumor imaging will be followed by surgical resection. Part 3- All patients will be treated with intensity modulation radiation therapy (IMRT) concurrent with weekly cisplatin 30mg/m2 or other standard of care chemoradiotherapy regimen.Once chemoradiotherapy is complete these patients will receive durvalumab 750 mg every two weeks for 3 cycles. |
Drug: Durvalumab
Subjects will receive durvalumab, 750 mg every 2 weeks by IV infusion over approximately 1 hour (± 5 minutes).
Other Name: MEDI4736
Drug: Carboplatin Carboplatin is commercially available and approved by the US FDA for use in patients with ovarian cancer.
Other Name: Paraplatin
Drug: Nab-paclitaxel Nab-paclitaxel is commercially available and approved by the US Food and Drug Administration (FDA) for use in patients with metastatic breast cancer, metastatic pancreatic cancer, and for the treatment of locally advanced or metastatic NSCLC.
Other Name: Abraxane
Drug: Cisplatin Cisplatin is commercially available and approved by the US Food and Drug Administration (FDA) for the treatment of advanced bladder, ovarian and testicular cancer. It has been widely studied in a variety of solid tumor types.
Procedure: Surgical resection Surgical therapy will be at the discretion of the treating surgeon per standard of care.
Radiation: IMRT "involved field radiation" will refer to areas demonstrated to harbor disease on pathology, and not elective areas
Other Name: Intensity-modulated radiation therapy
|
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Adequate bone marrow function as demonstrated by:
Adequate hepatic and renal function as demonstrated by:
Creatinine clearance (CrCL) > 40 mL/min as measured via Cockcroft-Gault
Exclusion Criteria:
Low-risk HPV+ disease of the oropharynx, defined as meeting all of the following criteria:
Other prior or concomitant malignancies with the exception of:
Contact: Melissa Flores | 919-966-4432 | melissa_flores@med.unc.edu | |
Contact: Lori Stravers | 919-966-8535 | lori_stravers@med.unc.edu |
United States, North Carolina | |
Lineberger Comprehensive Cancer Center at University of North Carolina Chapel Hill | Recruiting |
Chapel Hill, North Carolina, United States, 27599 | |
Contact: Jared Weiss, MD 919-843-7718 jared_weiss@med.unc.edu | |
Principal Investigator: Jared Weiss, MD | |
United States, Tennessee | |
Vanderbilt University Medical Center | Recruiting |
Nashville, Tennessee, United States, 37232 | |
Contact 800-811-8480 cip@vumc.org | |
Principal Investigator: Michael Gibson, MD, PhD |
Principal Investigator: | Jared Weiss, MD | University of North Carolina, Chapel Hill |
Tracking Information | |||||||||
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First Submitted Date ICMJE | May 26, 2017 | ||||||||
First Posted Date ICMJE | June 2, 2017 | ||||||||
Last Update Posted Date | July 1, 2020 | ||||||||
Actual Study Start Date ICMJE | December 19, 2017 | ||||||||
Estimated Primary Completion Date | September 1, 2021 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
Pathologic complete response rate (pCRR) after induction chemotherapy with carboplatin, nab-paclitaxel, and durvalumab in previously untreated stage III and IV SCCHN amenable to surgical resection [ Time Frame: After surgery (approximately 8-12 weeks after start of study treatment) ] The pCRR will be assessed via surgical pathology report. Pathologic complete response will require no viable cancer cells on the surgical pathology report after neoadjuvant treatment with carboplatin, nab-paclitaxel and durvalumab.
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures | Same as current | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Carboplatin, Nab-Paclitaxel, Durvalumab Before Surgery and Adjuvant Therapy in Head and Neck Squamous Cell Carcinoma | ||||||||
Official Title ICMJE | Multimodality Therapy With Induction Carboplatin/Nab-Paclitaxel/Durvalumab Followed by Surgical Resection and Risk-adapted Adjuvant Therapy for the Treatment of Locally-Advanced and Surgically Resectable Squamous Cell Carcinoma of the Head and Neck | ||||||||
Brief Summary |
Participants in this study have a type of cancer called squamous cell carcinoma of the head and neck (SCCHN). Their SCCHN has spread around the area where the cancer first started. This is called locally-advanced SCCHN. These participants are eligible for surgery. Previous research with a similar therapy regimen resulted in high rates of cancer shrinkage, high rates of avoiding radiation and its side effects, high cure rate and good quality of life. Radiation can be very toxic. The purpose on this study is to try to avoid radiation. If the participants are not on this study they would be receiving radiation as it is standard treatment of their cancer. In the last study with a similar regimen, about a third of cancers had a pathologic complete response with the first part of the study. This means that the chemotherapy had killed the cancer. The investigators are trying to improve the regimen further with a goal of increasing this rate of complete response to the first part of therapy. The investigators also hope that by improving results in the first part, that more people will be cured and that long term quality of life (especially speech and swallowing) will be improved, both compared to standard therapies and to the last study. Doctors do not know how this therapy will effect the participants. There is no guarantee that this study will benefit the participants. The prior study used a combination of chemotherapy consisting of carboplatin, paclitaxel and a third targeted anti-cancer drug. In this study the investigators are testing the combination of carboplatin, nano-albumin bound paclitaxel and durvalumab. Nano-albumin bound paclitaxel has been shown to be more active against other types of squamous cancers than regular paclitaxel. It is FDA approved for squamous lung cancer, but experimental for head and neck cancer. Durvalumab is an experimental drug that uses the body's own immune system to fight the cancer. Doctors hope that combining Durvalumab with 2 chemotherapy drugs will be effective in treating SCCHN. Durvalumab on its own has been studied in patients with SCCHN and initial results have shown that some subjects' cancer has responded to it. The purpose of this study is to test a combination of chemotherapy to hopefully both increase the number of subjects that respond to therapy while also decreasing the number of side effects that subjects experience. |
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Detailed Description |
STUDY OBJECTIVES Primary Objective: Estimate the pathologic complete response rate (pCRR) after induction chemotherapy with carboplatin, nab-paclitaxel, and durvalumab in previously untreated stage III and IV SCCHN amenable to surgical resection Secondary Objectives:
Translational/Exploratory Objectives:
PROCEDURES This is a single-arm, nonrandomized phase II trial consisting of 3 parts. After informed consent and screening, pre-induction, risk levels will be assessed clinically, by a combination of physical exam and imaging. Part 1: All patients will then receive 6 weeks of induction chemotherapy in Part 1 comprised of weekly cycles of carboplatin and nab-paclitaxel for 6 cycles in combination with durvalumab administered once every two weeks for 5 cycles (Day 1 of the weeks 1, 3, 5, 7, and 9). Part 2: Within a 1-4 the week window post induction, tumor imaging will be followed by surgical resection. Part 3: After surgery, patients will be stratified into one of 3 risk categories based on their disease pathology, assigned a treatment group based on their risk. Low risk patients with receive durvalumab once every two weeks for 3 cycles, while medium risk or high risks groups will receive concurrent chemoradiation therapy followed by durvalumab once every two weeks for 3 cycles. Follow up After completion of study therapy (which will vary by study arm) patients will be evaluated every three months during follow up for progression over a period of 18 months. Each follow up visit will include physical examination, CT or MRI imaging of the neck. Chest imaging will be obtained (or not) as indicated by standard of care. After the first 18 months, patients will be followed-up per standard of care, with documentation in the case report form (CRF) limited to progression and survival noted at their standard of care visits. If a patient should move away or otherwise be lost to in-person follow up but is amenable to telephone follow up, this will be permitted during the standard of care follow up period. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
39 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | September 1, 2026 | ||||||||
Estimated Primary Completion Date | September 1, 2021 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT03174275 | ||||||||
Other Study ID Numbers ICMJE | LCCC 1621 | ||||||||
Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | UNC Lineberger Comprehensive Cancer Center | ||||||||
Study Sponsor ICMJE | UNC Lineberger Comprehensive Cancer Center | ||||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | UNC Lineberger Comprehensive Cancer Center | ||||||||
Verification Date | June 2020 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |