Neoplasms

All Conditions

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Carcinoma

Carcinoma, Squamous Cell

Oropharyngeal Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

This is a non-randomized study, with all patients undergoing de-intensified post-operative cisplatin-based chemoradiation. Dosage level and duration of administration will be determined by whether the patient is high risk or not as assessed by the treating investigator.

* High risk patients who are patients with positive margins, extranodal extension, or ≥5 positive lymph nodes will receive radiation dose of 50 Gy in 25 fractions over 5 cycles on Days 1, 8, 15, 22, and 29 of radiation treatment.
* All other patients will receive radiation dose of 30 Gy in 15 fractions over 3 cycles on Days 1, 8 and 15 of radiation treatment.

Cisplatin-based Radiation Therapy

* High risk patients who are patients with positive margins, extranodal extension, or ≥5 positive lymph nodes will receive 5 cycles of weekly chemotherapy of cisplatin 40mg/m2 given intravenously (IV) on Days 1, 8, 15, 22, and 29 of radiation.
* All other patients will receive 3 cycles of weekly chemotherapy of cisplatin 40mg/m2 given intravenously (IV) on Days 1, 8 and 15 of radiation.

Cisplatin Chemotherapy

Amy Oppenheim

Kortnee Calkins

Vanessa Vasco

Marina Marquez

Zachary S Zumsteg, MD

This study will enroll patients with HPV-associated oropharyngeal cancer, undergoing resection of all gross visible disease at the primary site and in the lymph nodes. A total of 40 patients who have had or will require surgery to remove cancer cells prior to starting chemoradiation may be enrolled. All eligible patients will receive de-intensified cisplatin-based chemoradiation, with high-risk patients receiving a higher dose and longer treatment period than other patients on the study. The study will assess whether a de-intensified version of standard chemoradiation treatment will be just as effective in treating HPV-associated oropharyngeal cancer while causing less side effects than standard dosing.

This is a single arm phase II study that will enroll patients with HPV-associated oropharyngeal cancer, undergoing resection through trans-oral robotic surgery (TORS) of all gross visible disease at the primary site and in the lymph nodes. A total of 36 patients at Cedars-Sinai Medical Center and its affiliates (Tower Hematology-Oncology, Torrance Memorial Physician Network) who have had or will require surgery to remove cancer cells prior to starting chemoradiation may be enrolled. All eligible patients will receive de-intensified cisplatin-based chemoradiation, with high-risk patients receiving a higher dose and longer treatment period than other patients on the study. The treatment period will last 3 to 5 weeks depending on whether the patient is considered high-risk or not. The study will assess whether a de-intensified version of standard chemoradiation treatment will be just as effective in treating HPV-associated oropharyngeal cancer while causing less side effects than standard dosing.

Trial of De-Intensified Post-operative Chemoradiation Following Robotic Surgery for HPV-positive Oropharyngeal Cancer

IIT2019-20-Zumsteg-HPVOPC: Phase II Trial of De-Intensified Post-operative Chemoradiation Following Robotic Surgery for HPV-positive Oropharyngeal Cancer

Proportion of patients alive and without evidence of local, regional, or distant recurrence at 2 years from study enrollment.

Proportion of patients alive, based on time from enrollment to death from any cause.

Proportion of patients without recurrence at the primary site, based on time from enrollment to local recurrence, irrespective of prior regional or distant recurrence. Death from causes unrelated to cancer is a competing event.

Proportion of patients without recurrence in the cervical lymph nodes, based on time from enrollment to regional recurrence, irrespective of prior local or distant recurrence. Death from causes unrelated to cancer is a competing event.

Proportion of patients without local recurrence or regional recurrence, as defined above, based on the time from enrollment to the first evidence of either local or regional recurrence, irrespective of prior distant recurrence. Death from causes unrelated to cancer is a competing event.

Proportion of patients without distant recurrence, based on time from enrollment to distant recurrence, irrespective of prior local or regional recurrence. Distant metastasis includes any recurrent disease outside of the head and neck, cervical lymph nodes, or retropharyngeal lymph nodes. Death from causes unrelated to cancer is a competing event.

Proportion of patients without oropharyngeal cancer-related or treatment-related death, based on time from enrollment to death from oropharyngeal cancer or treatment. Death from other causes is a competing event.

PRO-CTCAE responses are scored from 0 to 4 (or 0/1 for absent/present), with lower scoring indicating an absence of symptoms to higher scoring reflecting higher severity of symptoms.

The scale ranges from 0 to 4 (0 - no, 2 - sometimes, 4- yes) for each question identifying problems with hearing loss, as self-reported by patients. The total number of points for the 25 questions range from 0 to 100, with 0 indicating no handicap to 100 indicating total handicap.

The EORTC QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL, and six single items. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems. Most questions are scored 1 to 4, with exception to global health questions scored from 1 to 7. The raw scores are then standardized by a linear transformation, so that scores range from 0 to 100; a higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms.

XeQOLS is a patient-reported, 15-item scale that measures four domains: physical functioning, pain/discomfort, personal/psychologic functioning, and social functioning. Patient responses to all four domains are averaged, and the total scores range from 0 to 4; an increased xerostomia burden is indicated by a higher score.

The EQ-5D-5L descriptive system comprises of five dimensions: (MOBILITY, SELF-CARE, USUAL ACTIVITIES, PAIN / DISCOMFORT and ANXIETY / DEPRESSION), with each dimension having five response levels: no problems, slight problems, moderate problems, severe problems, unable to /extreme problems - severity level of each dimension are coded from 1 to 5, respectively. The visual analog scale (EQ VAS) attached to this questionnaire records the respondent's overall self-rated perception of current health status on a vertical visual analogue scale, where the endpoints are scored from 0 to 100, 100 being the 'The best health you can imagine' and 0 indicating 'The worst health you can imagine'

The MDADI is a patient-reported, 20-item scale that quantifies four domains: an individual's global (G), physical (P), emotional (E), and functional (F) perceptions of their swallowing ability. Two summary scores can be obtained from the MDADI: 1) global and 2) composite. The global scale is a single question, scored individually, to assess the overall impact that swallowing abilities have on quality of life ("my swallowing impacts my day-to-day life"). The composite MDADI score summarizes overall performance on remaining 19-items of the MDADI, as a weighted average of the physical, emotional, and functional subscale questions. Summary and subscale MDADI scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning). Five possible responses to the items on the MDADI are: strongly agree, agree, no opinion, disagree, and strongly disagree, and scored on a scale of 1 to 5 respectively.

The difference between the proportion of patients alive and without evidence of local, regional, or distant recurrence at 2 years from study enrollment, in high-risk and intermediate subgroups.

Cedars-Sinai Medical Center

Assistant Professor

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Vaccines

Immunomodulating Agents

Interleukin-12

INO-3112 dosing during chemoradiotherapy plus immunotherapy dosing after chemoradiotherapy in an adjuvant setting and vaccine boost one year after last vaccine dosing.

INO-3112 dosing during chemoradiotherapy, and vaccine boost one year after last vaccine dosing.

Standard chemoradiotherapy without immunotherapy

INO-3112 i.e. the combination of VGX-3100 and INO-9012, specifically:

* VGX-3100 (HPV16 and HPV18 E6-E7 DNA vaccine) will be administered at 3 mg per plasmid (6 mg total DNA)
* INO-9012 (IL-12 DNA plasmid) will be administered at 1 mg per dose will be administered using the CELLECTRA® electoporation device

INO-3112 vaccine

The whole pelvis will be irradiated with 45 - 50.4 Gy in 25-28 fractions in fractions of 1.8 Gy over 5 weeks daily.

Those patients with pelvis positive and/or para-aortic positive lymph nodes should be treated with an elective dose to the para-aortic area of 45 Gy in fractions of 1.6-1.8 Gy in 25-28 fractions.

Pelvic and para-aortic nodes known to contain gross/macroscopically visible disease and heavily involved parametria or tumor areas that may lie beyond the high-dose range of brachytherapy should be treated with additional small volume boost of EBRT to a total dose of 60-65 Gy using a combination of either sequential and/or concomitant boost. Fractions of 1.8-2 Gy can be used in the sequential boost.

Radiotherapy (Extrernal beam radiotherapy + brachytherapy)

Cisplatin chemotherapy will be administered i.v. at a dose of 40 mg/m2 (total 5 cycles during week 1-5) weekly in concomitance with RT with the total dose not to exceed 70 mg per week.

Cisplatin chemotherapy

Fernanda Herrera

George Coukos

The aim of this study is to assess the potential benefit of the addition of immunotherapy with VGX-3100 and INO-9012 (i.e. INO-3112) to concomitant CRT or, to concomitant CRT and continued as adjuvant in patients with locally advanced cervical cancer.

Safety run-in: To test the safety of CRT combined with immunotherapy with INO-3112. This safety run-in phase will include the first 3 patients treated in each of the two INO-3112 combination arms who are exposed to at least two immunotherapy doses and evaluate whether the combination does not pose undue immediate risks to the patients further enrolled in the trial.

Phase II:To demonstrate sufficient activity in the experimental combination arms to warrant a further phase III conclusive trial based on progression free survival (PFS) at 18 months assessed by RECIST by the local investigator. The efficacy will be assessed within each experimental arm while the standard arm will serve as a reference arm to check the reliability of the results.

A Phase II Clinical Trial of Chemo-radiotherapy in Combination With INO-3112 in Patients With Locally Advanced Cervical Cancer

In order to ensure adequate safety of the combination treatment, a safety run-in will be performed. This safety run-in phase will include the first 3 patients treated in each of the experimental arms (arms A \& B) exposed to at least two immunotherapy doses. The acute safety of the combination of INO-3112 with concomitant CRT will be evaluated similar to a phase I "3+3" safety design. The safety evaluation will be done by the Data Safety Monitoring Board who will invoke an IDMC evaluation of the whole study if undue safety signals are observed.

Acute toxicity is defined as a grade 3 or more related AEs occurring between the first dose of vaccine administration and up to 14 days after the second dose of immunotherapy. Adverse events are graded according to the NCI CTCAE v4.0. Use of narcotics will be reviewed on case-to-case basis by a medical review team to assess its relevance towards the safety evaluation

Progression Free Survival at 18 months assessed by local investigator

Inovio Pharmaceuticals

Centre Hospitalier Universitaire Vaudois

European Organisation for Research and Treatment of Cancer - EORTC

Symptoms and General Pathology

Digestive System Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Pain

Stomatitis

Xerostomia

Mucositis

Oral Ulcer

Laryngeal Diseases

Gastroenteritis

Gastrointestinal Diseases

Mouth Diseases

Mitogens

Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course.

Participants received a single IV dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.

Placebo

palifermin

Commercially available cisplatin was administered as an intravenous infusion at a dose of 100 mg/m\^2 on Days 1, 22, and 43.

cisplatin chemotherapy

Radiotherapy was delivered in 200 cGy daily fractions, 5 days a week.

Radiotherapy

The purpose of this research study is to test the safety and effectiveness of palifermin to determine if weekly doses can be safely administered to reduce the incidence (occurrence of), duration (length of time) and severity (amount of pain) of oral mucositis (painful sores in the mouth). Mucositis is a common side effect for patients receiving chemotherapy (cancer-killing drug) and radiotherapy (cancer-killing x-rays) for the treatment of head and neck cancer (HNC).

This study consisted of 2 phases. The acute oral mucositis (OM) evaluation phase includes the time from randomization to the time of severe OM (WHO Grade 3 or 4) resolution (up to Week 12 or up to Week 15 for participants whose severe OM is not resolved at Week 12). In the acute OM evaluation phase, participants were randomized to receive either a single IV dose of palifermin or placebo at 180 μg/kg, 3 days before the start of radiotherapy, plus 7 once-weekly palifermin or placebo doses at the same dose level during a 7-week radio/chemotherapy course. In the long-term follow up phase, participants are followed until death, withdrawal of consent, or loss to follow-up. The long-term follow up phase is still ongoing.

Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer

Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Weekly Doses of Palifermin (rHuKGF) for the Reduction of Oral Mucositis in Subjects With Advanced Head and Neck Cancer Receiving Radiotherapy With Concurrent Chemotherapy (RT/CT)

Participants underwent evaluations of oral mucosal (OM) surfaces (mucositis assessments) 2 times weekly throughout radio/chemotherapy, and 2 times weekly thereafter until severe OM returned to grade ≤ 2 or until Week 15. During each evaluation, the following anatomical areas were assessed: upper lip; lower lip; right cheek; left cheek; right ventral \& lateral tongue; left ventral \& lateral tongue; floor of the mouth; hard palate; soft palate. A trained evaluator documented the findings using the World Health Organization (WHO) oral toxicity scale according to the following: Grade 0 = None; Grade 1 = Soreness, erythema; Grade 2 = Erythema, ulcers, ability to eat solids; Grade 3 = Ulcers, requires liquid diet; Grade 4 = Alimentation not possible.

The duration of severe oral mucositis (OM) was calculated as the number of days from the onset of severe OM (first time a WHO grade 3 or 4 was observed) to the day when severe OM was resolved (first time WHO grade 2 or less was observed after last WHO grade 3 or 4). Durations of 0 days were assigned to those participants who did not experience any WHO grade 3 or 4 during the study.

Time to onset of severe (WHO Grade 3 or 4) oral mucositis (OM) was analyzed using the Kaplan-Meier procedure.

Participants without an assessed event by the end of the acute OM evaluation phase were censored at the date of last assessment for severe OM.

The number of participants with grade 2 or higher xerostomia (dryness of the oral mucosa) at the Month 4 visit, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Dry Mouth/Xerostomia scale.

The average patient-reported mouth and throat soreness (MTS) score as reported on question 3 of the Oral Mucositis Weekly Questionnaire for Head and Neck Cancer \[OMWQ-HN\]): "How much mouth and throat soreness did you experience in the past 24 hours?" Participants answered on a scale from 0 (no soreness) to 4 (extreme soreness).

For each participant, an average patient-reported mouth and throat soreness score was calculated by dividing the sum of the MTS scores at each assessment by the total number of assessments.

The total dose of opioid analgesics (mg of intravenous \[IV\] morphine equivalents) used by all participants.

Participants with at least one reported administration of opioid analgesic (parenteral, peroral or transdermal) were considered to have received opioid analgesics. The total dose of opioid analgesics is the sum of all opioid analgesic administrations that have been converted to morphine equivalents.

Cisplatin was administered on Days 1, 22, and 43. An unplanned break in cisplatin refers to a delay of ≥ 5 days from the scheduled Day 22 or Day 43 cisplatin administration or a discontinuation of cisplatin for any reason.

Participants with a duration of 5 days or more without an administration of radiotherapy or who discontinue radiotherapy prior to completion of planned radiotherapy were considered to have an unplanned break in radiotherapy.

Amgen

Swedish Orphan Biovitrum

The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.

Participants received a single intravenous (IV) dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.

Palifermin

Total

Age, Continuous

Sex: Female, Male

Caucasian

Black

Hispanic

American Indian/ Alaska Native

Race/Ethnicity, Customized

Data available for 91 and 94 participants in each treatment group respectively.

Weight

Stage III

Stage IV A

Stage IV B

American Joint Committee on Cancer staging system.

Disease Stage

Oral Cavity

Oropharynx

Nasopharynx

Larynx

Hypopharynx

Tumor Site

Hans Olivecrona, MD PhD

Sample size calculations were based on the number of participants needed to detect, with 90% power and 5% type 1 error rate, at least a 25% difference in the incidence of severe OM between the treatment groups. A 25% absolute reduction in the incidence of severe OM from the placebo group was considered by investigators as clinically meaningful in this clinical setting.

Unknown

The Full Analysis Set included all randomized participants.

Number of Participants With Severe (Grade 3 or 4) Oral Mucositis

To protect the overall type 1 error, the Hochberg procedure was used to adjust for multiple statistical testing of the secondary efficacy endpoints.

Duration of Severe (WHO Grade 3 or 4) Oral Mucositis

Time to Onset of Severe (WHO Grade 3 or 4) Oral Mucositis

Number of Participants With Xerostomia at Month 4 (Grade 2 or Higher)

The Patient Reported Outcome-evaluable analysis set included all randomized patients with a valid Baseline assessment for MTS question 3 of the OMWQ-HN and either:

* At least 1 completed assessment each week for MTS up to withdrawal/Week 8, whichever came first, or
* 70% or greater overall compliance for MTS until withdrawal/Week 8.

Patient-Reported Mouth and Throat Soreness Score

Total Dose of Opioid Analgesics Used for Mucositis Within 15 Weeks

Number of Participants With Unplanned Breaks in Cisplatin Chemotherapy Treatment

Number of Participants With Unplanned Breaks in Radiotherapy

Participants received a single intravenous (IV) dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course. Chemotherapy consisted of 100 mg/m\^2 cisplatin administered by IV infusion on Days 1, 22, and 43.

Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course. Chemotherapy consisted of 100 mg/m\^2 cisplatin administered by IV infusion on Days 1, 22, and 43.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of De-Intensified Post-operative Chemoradiation Following Robotic Surgery for HPV-positive Oropharyngeal Cancer	NCT04502407	HPV Positive Or...	Cisplatin-based... Cisplatin Chemo...	18 Years -	Cedars-Sinai Medical Center
A Phase II Clinical Trial of Chemo-radiotherapy in Combination With INO-3112 in Patients With Locally Advanced Cervical Cancer	NCT02501278	Uterine Cervica...	INO-3112 vaccin... Radiotherapy (E... Cisplatin chemo...	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer	NCT00101582	Mucositis Solid Tumors Stomatitis Head and Neck C... Squamous Cell C...	Placebo palifermin cisplatin chemo... Radiotherapy	18 Years -	Swedish Orphan Biovitrum

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