Clinical trial NCT01333085: Everolimus, Carboplatin, and Paclitaxel in Locally Advanced Head and Neck Cancer That Cannot Be Removed by Surgery
Official title: Phase I/II Study of Induction Chemotherapy With Weekly RAD001, Carboplatin and Paclitaxel in Unresectable or Inoperable Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Head and Neck Cancer
Keywords: stage IV squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the larynx
stage IV verrucous carcinoma of the larynx
stage IV squamous cell carcinoma of the lip and oral cavity
stage IV verrucous carcinoma of the oral cavity
stage IV squamous cell carcinoma of the oropharynx
tongue cancer
Lead sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
Sponsor class: OTHER
First posted: 2011-04-11
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I/II trial is studying the side effects and best dose of giving everolimus together with carboplatin and paclitaxel in treating patients with locally advanced head and neck cancer that cannot be removed by surgery.

Detailed description: OBJECTIVES:

Primary

* To determine the maximum-tolerated dose of everolimus when combined with carboplatin and paclitaxel in chemonaïve patients with unresectable or inoperable locally advanced head and neck squamous cell carcinoma. (Phase I)
* To determine the safety profile of weekly everolimus in combination with carboplatin and paclitaxel in chemonaïve patients with unresectable or inoperable locally advanced head and neck squamous cell carcinoma. (Phase I)
* To determine the anti-tumor activity of this regimen, in terms of objective response rate of the combination, according to the RECIST criteria in these patients. (Phase II)

Secondary

* To identify molecular markers of resistance to this regimen in these patients.
* To assess objective response rate before and after completion of radiation therapy in these patients. (Phase II)

OUTLINE: This is a multicenter, phase I dose-escalation study of everolimus followed by a phase II study.

* Phase I: Patients receive paclitaxel IV over 1 hour, carboplatin IV over 1 hour, and escalating doses of oral everolimus on days 1, 8, and 15. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
* Phase II: Patients receive paclitaxel and carboplatin as in phase I and oral everolimus (at a dose determined in the phase I portion of the study) on days 1, 8, and 15. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

After the completion of combination therapy, patients may receive radiotherapy or surgery, at the investigator's discretion.

Blood samples are collected for translational research and molecular markers analysis at baseline and weeks 1, 4, and 9. Tissue samples are collected at baseline and periodically during the study for biomarker and other laboratory analysis.

After completion of study treatment, patients are followed up at 14 days and periodically thereafter.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx

  * Locally advanced disease (T4 N0-N3 disease)
  * Unresectable disease OR resectable disease with surgery contra-indication
  * No stage I, II, III, or IVc disease
* Measurable lesions defined as those accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
* No known brain metastases (cerebral CT scan is not required if no symptom is present)

PATIENT CHARACTERISTICS:

* WHO performance status 0-2
* Life expectancy \> 3 months
* Absolute neutrophil count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 9 g/dL
* Total bilirubin ≤ 1.25 times upper limit of normal (ULN)
* Transaminases ≤ 2.5 times ULN
* Alkaline phosphatase ≤ 5 times ULN
* Creatinine clearance ≥ 60 mL/min
* Glycemia ≤ 1.5 times ULN
* Cholesterol level ≤ 7.30 mmol/L
* Serum total protein normal
* Oxygen saturation \> 88%
* Able to swallow pills
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 3 months after completion of study treatment
* No preexisting neuropathy ≥ grade 2
* No uncontrolled disease including any of the following:

  * Diabetes
  * Hypertension
  * Symptomatic congestive heart or pulmonary failure
  * Renal or hepatic chronic disease
  * Severe infectious disease
* No active hemorrhagic syndrome
* No prior history of cancer within the past 5 years, except in situ cervical cancer and basal cell skin carcinoma
* No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
* Registration in a national health care system (CMU included)
* Not eligible for organ preservation program

PRIOR CONCURRENT THERAPY:

* No prior therapy for this cancer
* No prior chemotherapy unless received for treatment of another primary tumor considered in remission
* No prior investigational drug
* More than 30 days since prior participation in another therapeutic trial
* No prior or concurrent radiotherapy (except anterior radiotherapy) unless received for treatment of another primary tumor considered in remission
* No concurrent CYP3A4 strong inhibitors (e.g., azole antimycotics \[itraconazole, ketoconazole\], HIV protease inhibitor \[ritonavir\], erythromycin, anti-epileptic drugs \[phenytoin, carbamazepine\])
* No concurrent anti-coagulant therapy

Primary outcomes:
measure: Maximum tolerated dose
timeFrame: weekly
measure: objective response rate
timeFrame: 9 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Clichy
country: France
facility: Hopital Beaujon
city: Lyon
country: France
facility: Centre Léon Berard
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Hôpital Privé Saint Joseph
city: Toulouse
country: France
facility: Institut Claudius Regaud
Study officials:
affiliation: Hopital Beaujon
name: Sandrine Faivre
role: PRINCIPAL_INVESTIGATOR
References: