This research study is evaluating a drug called buparlisib (BKM120) as a possible treatment for locally advanced head and neck squamous cell cancer.
* This phase Ib study is combining standard chemoradiotherapy with weekly cisplatin and BKM120 to assess tolerability of this combination in high risk patients with locally advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN). The investigators will also obtain preliminary information about the efficacy of this treatment. * The participant will receive the study drug buparlisib once daily, by mouth, for 45 days. The participant will be given a study drug-dosing diary for each cycle. It will include special instructions for taking the study drug at home. * The investigators are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects, not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study before and how well they have tolerated their doses. * All participants will receive weekly cisplatin injection. Cisplatin will be given intra-venously (IV) on days: (1, 8, 15, 22, 29, 36 and 43) at DFCI. * All participants will receive daily radiotherapy with intensity-modulated radiotherapy (IMRT) for 7 weeks, delivered at DFCI. IMRT is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. * The investigators would like to keep track of the participant's medical condition. Follow-up will continue every 4 to 12 weeks after the end of treatment for the first year and at the investigator's discretion thereafter.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
23
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Maximum Tolerated Dose of Cisplatin
The trial uses 3+3 design to determine maximum tolerated dose (MTD).
Time frame: While on treatment, up to 66 days
Maximum Tolerated Dose of BKM120
The trial uses 3+3 design to determine maximum tolerated dose (MTD).
Time frame: While on treatment, up to 66 days
Best Overall Response
The best overall response for each patient is given per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1) criteria: Complete Response (CR) - Disappearance of all target and non-target lesions and lymph node short axis is \<10 mm and no new lesions Partial Response (PR) * Disappearance of target lesions and \>=1 persisting non-target lesion or tumor marker levels above normal limits and no new lesions or * \>=30% decrease in sum of target lesion diameter and no new lesions Stable Disease (SD) \- Less than 5 mm increase in target lesion diameter unless it results in a \>=20% increase in diameter and \>=1 persisting non-target lesion or tumor marker levels above normal limits and no new lesions Progressive Disease (PD) * \>20% increase in target lesion diameter, must be an absolute increase of 5mm or * Substantial worsening in non-target lesion or * New lesion present
Time frame: Measured at end of treatment, up to 66 days
Median Time to Progression
The median amount of time from baseline to progression and/or death. Patients known to be alive at last contact are censored at last contact. All patients alive at 24 months from baseline are censored at 24 months.
Time frame: Up to 24 months (Progression is defined using RECIST v1.0 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions)
24 Month Overall Survival
The probability of survival at 24 months using Kaplan-Meier estimates. Patients alive at 2 years are censored at 2 years.
Time frame: Up to 24 months
Median Anxiety Score Change
The median change in score on the Generalized Anxiety Disorder - 7 (GAD-7) questionnaire from baseline to cycle 9.GAD-7 has 7 questions and each question has score from 0 to 3. Sum score of all questions will be used as the final score. The final score ranges from 0 to 21. Higher score represents worse anxiety.
Time frame: From baseline to cycle 9, up to 66 days.
Median Depression Score Change
The median change in score on the Patient Health Questionnaire - 9 (PHQ-8) from baseline to cycle 9. PHQ-9 has 9 questions and each question has score from 0 to 3. Sum score of all questions will be used as the final score. The final score ranges from 0 to 27. Higher score represents worse depression.
Time frame: From baseline to cycle 9, up to 66 days.
P13K Status by Response
Phosphoinositide 3-kinase (PI3K) biomarker status, either positive or negative, analyzed using established methods from tumor biopsies. P13K status is reported by response, either responder (CR or PR) or non-responder (SD or PR).
Time frame: Biopsies drawn up to 10 days from registration. Response measured at from baseline to cycle 9, up to 66 days.
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