Phase II Trial Evaluating the Efficacy of Palbociclib in Combination With Carboplatin for the Treatment of Unresectable Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to test the effectiveness (how well the drug works), safety, and tolerability of the investigational drug combination of palbociclib (Ibrance) plus carboplatin in patients with metastatic head and neck squamous cell cancer.

Official Title
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A Multi-Center Open Label Single Arm Phase II Trial Evaluating the Efficacy of Palbociclib in Combination With Carboplatin for the Treatment of Unresectable Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Conditions
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Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
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* Drug: Palbociclib
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically documented progressive squamous cell head and neck cancer with or without metastases, not amenable to curative treatment; or the patient has documented refusal of curative treatment. ECOG performance status of 0-2. Eastern Cooperative Oncology Group Performance Status: an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death. Presence of measurable disease by CT scan per RECIST v1.1. Age ≥18 years. Life expectancy of ≥12 weeks. Women of childbearing potential must have a negative serum or urine pregnancy test at time of screening and confirmed within 3 days prior to treatment. Women not of child-bearing potential will be defined as all women older than age 50 and anovulatory for 12 months. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Adequate organ and marrow function Exclusion Criteria: Previous treatment with cytotoxic chemotherapy therapy in the recurrent/metastatic setting. Previous treatment with non-cytotoxic agents in the recurrent/metastatic setting is permitted. Gastrointestinal abnormalities causing impaired absorption precluding administration of oral medications. Evidence of untreated or progressive brain metastases, spinal cord compression, or carcinomatous meningitis. A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol. Patients (male and female) having procreative potential who are not willing or not able to use adequate contraception. Women who are pregnant or breast-feeding. Patients residing in prison. Prior experimental therapy within 30 days of enrollment. Availability of curative treatment option for the patient's cancer, whether surgery, chemotherapy, radiation, or combination thereof, unless the patient has documented refusal of curative treatment. Current use or anticipated inability to avoid use of drugs that are known strong CYP3A4/5 inhibitors (atazanavir, boceprevir, conivaptan, clarithromycin, grapefruit or grapefruit juice, indinavir, itraconazole, ketoconazole, nelfinavir, nefazodone, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole ). Current use or anticipated inability to avoid use of drugs that are known strong CYP3A4/5 inducers (carbamazepine, dexamethasone, fosphenytoin, phenytoin, phenobarbital, rifabutin, rifampin, rifapentine, St. John's wort). Patients with a history of severe allergic reaction to cisplatin or carboplatin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Palbociclib and Carboplatin<br>Treatment with Palbociclib and Carboplatin for up to 6 cycles: Palbociclib (Ibrance) (PO), dose= 125 mg PO daily, days=1-14, cycle length: 21 days Carboplatin (IV), dose= AUC 5, day= 1, cycle length: 21 days Maintenance Palbociclib after 6 cycles Palbociclib (Ibrance) 125 mg PO daily, days 1-21, cycle length: 28 days | Drug: Palbociclib<br>* Palbociclib (Ibrance) (PO), dose= 125 mg PO daily, days=1-14, cycle length: 21 days Maintenance Palbociclib: Palbociclib (Ibrance) 125 mg PO daily, days 1-21, cycle length: 28 days<br>Drug: Carboplatin<br>* Carboplatin (IV), dose= AUC 5, day= 1, cycle length: 21 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Disease Control Rate (DCR) | The primary clinical objective of this trial is to estimate disease control rate (DCR) at 12 weeks in patients with metastatic head and neck squamous cell cancer treated with carboplatin and palbociclib. DCR will be defined as either CR (Complete Response: Disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.), PR (Partial Response: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.) or SD (Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.) at 12 weeks. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression Free Survival Time | Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression. Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions. Estimated using a Kaplan-Meier analysis. | Up to 2 Years | 
| Median Overall Survival Time | Overall survival is defined as the time from study enrollment to death from any cause. Estimated using a Kaplan-Meier analysis. | Up to 2 Years | 
| Number of Treatment-related Toxicities | Number of adverse events believed to be related (i.e., possibly, probably, or definitely) to palbociclib in combination with carboplatin, reported by grade according to the Common Terminology for Adverse Events version 4.0 (CTCAE v4). | Up to 2 years |