Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Laryngeal Diseases

Carcinoma, Verrucous

Laryngeal Cancer

Hypopharyngeal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

Panitumumab

Antineoplastic Agents, Immunological

Patients undergo standard fractionation radiotherapy (IMRT or 3D CRT) once daily, 5 days a week, for 7 weeks. Patients receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy.

Patients undergo accelerated fractionation radiotherapy (IMRT or 3D CRT) once or twice daily, 5 days a week, for 6 weeks. Patients receive panitumumab IV over 30-90 minutes 1 week prior to and on days 15 and 36 of radiotherapy.

panitumumab

cisplatin

3-dimensional conformal radiation therapy

Patients undergo accelerated fractionation radiotherapy

accelerated radiation therapy

intensity-modulated radiation therapy

Lillian L. Siu, MD, FRCPC

John Waldron, MD

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy in higher doses over a shorter period of time may kill more tumor cells and have fewer side effects. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving standard radiation therapy together with high-dose cisplatin is more effective than giving higher-dose radiation therapy together with panitumumab in treating patients with locally advanced head and neck cancer.

PURPOSE: This randomized phase III trial is comparing two radiation therapy regimens to see how well they work when given together with cisplatin or panitumumab in treating patients with locally advanced stage III or stage IV head and neck cancer.

OBJECTIVES:

Primary

* To compare the progression-free survival (PFS) of patients with locally advanced squamous cell carcinoma of the head and neck treated with standard fractionation radiotherapy and high-dose cisplatin vs accelerated fractionation radiotherapy and panitumumab.

Secondary

* To compare overall survival of patients treated with these regimens.
* To compare local and regional PFS of patients treated with these regimens.
* To compare distant metastasis in patients treated with these regimens.
* To compare adverse events, including late radiotherapy-related adverse events in patients treated with these regimens.
* To compare quality of life (QOL) of patients treated with these regimens.
* To compare swallowing-related QOL of patients treated with these regimens.
* To compare economic evaluation (cost effectiveness analysis and cost utility), including both healthcare utilization and indirect costs.

OUTLINE: This is a multicenter study. Patients are stratified according to T category (T1-3 vs T4), nodal status (N0-1 vs N2 vs N3), radiotherapy delivery modality (intensity-modulated \[IMRT\] vs 3-D conformal \[3D CRT\]), anatomic location (hypopharynx vs oral cavity vs oropharynx vs larynx), and participation in the optional swallowing impairment substudy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients undergo standard fractionation radiotherapy (IMRT or 3D CRT) once daily, 5 days a week, for 7 weeks. Patients receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy.
* Arm II: Patients undergo accelerated fractionation radiotherapy (IMRT or 3D CRT) once or twice daily, 5 days a week, for 6 weeks. Patients receive panitumumab IV over 30-90 minutes 1 week prior to and on days 15 and 36 of radiotherapy.

Treatment in both arms continues in the absence of disease progression or unacceptable toxicity.

Quality of life (QOL) (FACT-H\&N), swallowing-related QOL (MDADI, SWAL-QOL), swallowing function (FOIS), and economic evaluations (Lost Productivity questionnaire) are assessed periodically during the study.

After completion of study treatment, patients are followed periodically for at least 5 years.

Radiation + Cisplatin or Panitumumab in Locally Advanced Stage III or Stage IV Head and Neck Cancer

A Phase III Study of Standard Fractionation Radiotherapy With Concurrent High-Dose Cisplatin Versus Accelerated Fractionation Radiotherapy With Panitumumab in Patients With Locally Advanced Stage III and IV Squamous Cell Carcinoma of the Head and Neck

The progression event is defined by first event of the following,

Local-regional progression or recurrence Distant metastasis Non-protocol RT, chemotherapy, or biologic therapy without documentation of the site of failure Surgery of primary site with tumour present/unknown Neck dissection with tumour present/unknown, \> 15 weeks from end of RT Death due to study cancer or from unknown causes or any other reason

Number of patients with and without progression event will be reported.

Overall survival is defined as the time interval between the date of randomization to date of death from any cause (calculated in months). Otherwise, survival is censored at the last date that the patient is known to be alive.

Number of death and alive patients will be reported.

NCIC Clinical Trials Group

Adverse events were collected on patients who have received the protocol treatment, which were 156 patients in Cisplatin arm and 159 patients in Panitumumab arm, as reported in the Participant Flow.

Patients undergo standard fractionation radiotherapy (IMRT or 3D CRT) once daily, 5 days a week, for 7 weeks. Patients receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy.

cisplatin: Given IV

3-dimensional conformal radiation therapy: Patients undergo radiotherapy

intensity-modulated radiation therapy: Patients undergo radiotherapy

Patients undergo accelerated fractionation radiotherapy (IMRT or 3D CRT) once or twice daily, 5 days a week, for 6 weeks. Patients receive panitumumab IV over 30-90 minutes 1 week prior to and on days 15 and 36 of radiotherapy.

panitumumab: Given IV

3-dimensional conformal radiation therapy: Patients undergo radiotherapy

accelerated radiation therapy: Patients undergo accelerated fractionation radiotherapy

intensity-modulated radiation therapy: Patients undergo radiotherapy

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Performance Status:

0: Fully active, able to carry on all pre-disease performance without restriction

1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work

ECOG Performance Status

Anatomic Location

Smoking

Wendy Parulekar

The log rank test stratified by the stratification factors at randomization was used to compare the difference in PFS between two treatment arms.

Progression-free Survival (PFS) Rate

Overall Survival Rate

Overall Study

Digestive System Diseases

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Micronutrients

Hematinics

Vitamins

Capecitabine

Leucovorin

Fluorouracil

Levoleucovorin

Oxaliplatin

Folic Acid

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

Participants will initiate therapy with neoadjuvant chemotherapy of either six (6) 14-day cycles of 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX) or four (4) 21-day cycles of capecitabine+oxaliplatin (CAPOX). Participants will then receive chemo-radiation therapy according to Plan I as follows:

Plan I (5 weeks):

* MRI-guided pelvic IMRT to the Planning Tumor Volume (PTV) at a dose of 50 Grays (gy) delivered in 25 fractions (fx) over 5 weeks.
* Concurrent chemotherapy beginning on Day 1 of RT either:

  * 5-FU delivered 5 or 7 days per week.
  * Capecitabine (Xeloda) delivered 5 days per week.

After completing Plan I, participants achieving complete Clinical Response (cCR) after completing Plan I chemo-radiation will forgo the Plan II boost and continue to follow-up. Participants not achieving cCR will begin Plan II, one week after completing Plan I.

Plan II boost RT (1 week): For participants not achieving cCR after chemo-radiation. Participants will receive MRI-guided accelerated radiation therapy (ART) boost to the primary tumor.

Participants achieving a cCR will continue to follow-up. Participants still showing residual tumor will undergo standard of care treatment including surgery and adjuvant chemotherapy per institutional guidelines during follow-up.

MRI-guided pelvic IMRT to the Planning Tumor Volume (PTV) at a dose of 50 Grays (gy) delivered in 25 fractions (fx) over 5 weeks.

Intensity-modulated radiation therapy

5-FU dose of 400 mg/m2 will be administered intravenously (IV) over 5-15 minutes beginning on Day 1; then a dose of 2400 mg/m2 via continual infusion (CI) over 4446-478 hours total dose during Days 1 and 2 of every 14-day cycle, for 4 to 6 cycles.

During SMART TNT Plan I, 5-FU dose of 225 mg/m2 per day will be administered via CI on Day 1 radiation therapy, delivered either 5 or 7 days per week.

5-fluorouracil

Leucovorin dose of 400 mg/m2 bolus will be administered intravenously (IV) on Day 1 of each 14-day cycle for 4 to 6 cycles, prior to SMART TNT Plan I radiation therapy.

Oxaliplatin dose of 85 mg/m2 will be administered intravenously (IV) on Day 1 of each 14-day cycle for 4 - 6 cycles.

Capecitabine will be administered orally at a dose of 825 mg/m2 via tablet twice per day (BID) on Day 1, 5 days per week.

MRI-guided Pelvic accelerated radiation therapy (ART) given over one week at one of the following dose levels :

* Dose level -1: 10 Gy delivered in 4 fractions
* Dose level 0: 12 Gy delivered in 4 fractions
* Dose level 1: 14 Gy delivered in 4 fractions
* Dose level 2: 16 Gy in delivered 4 fractions

Accelerated Radiation Therapy

Zuzel Rodriguez

Lorraine Portelance, MD

The purpose of this research study is to find out how safe and effective is treating patients with locally advanced rectal cancer (LARC) with chemotherapy first and then follow with radiation therapy to a higher dose than what is usually delivered and see if patients could have complete response and be spared from surgery.

SMART TNT for the Conservative Management of Locally Advanced Rectal Cancer

Selective Treatment With Magnetic Resonance Image Guided Pelvic Adaptive Radiation Therapy Combined With Total Neoadjuvant ChemoTherapy for the Conservative Management of Locally Advanced Rectal Cancer

Reported as the incidence of toxicity (adverse events and serious adverse events) in study participants after start of MRI-g Pelvic ART. Toxicity in study participants will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.

Reported as the incidence of grade 3 or higher acute and long-term toxicity by organ in study participants after start of study therapy. These toxicities will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.

Local control is defined as the stopping of cancer growth at the original primary site. The percentage of participants with documented local control after study therapy will be reported.

Distant metastasis is defined as cancer that has spread form the original (primary) tumor to distant organs and distant lymph nodes. The percentage of participants with documented distant metastasis after study therapy will be reported.

Disease-free survival is defined as the elapsed time after treatment that a person with disease lives without known disease recurrence. DFS rate will be reported as the percentage of participants without disease recurrence after start of treatment.

OS will be reported as the number of participants still alive after start of treatment.

The sensitivity and specificity of multiparametric magnetic resonance imaging (mpMRI) to measure tumor response will be reported as the percentage of real negatives during the course of treatment of study participants.

Patient-Reported Outcomes (PRO) will be measured using the 29-item NIH PROMIS questionnaire, a validated HRQOL measure that provides global levels of health-related quality of life. PROMIS has subscales of emotional distress, fatigue, pain, physical function, sleep disturbance, and satisfaction with social participation.

Health-related quality of life will be reported using Pittsburgh Sleep Quality Index (PSQI) which assesses patient-reported sleep quality over a 1-month time interval. The PSQI consists of 19 items including 7 sleep components (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction) that produce one global score. Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Radiation + Cisplatin or Panitumumab in Locally Advanced Stage III or Stage IV Head and Neck Cancer	NCT00820248	Head and Neck C...	panitumumab cisplatin 3-dimensional c... accelerated rad... intensity-modul...	18 Years -	Canadian Cancer Trials Group
SMART TNT for the Conservative Management of Locally Advanced Rectal Cancer	NCT05412082	Locally Advance...	Intensity-modul... 5-fluorouracil Leucovorin Oxaliplatin Capecitabine Accelerated Rad...	18 Years -	University of Miami

Spots Global Cancer Trial Database for accelerated radiation therapy