Know Cancer

or
forgot password

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)


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Head and Neck Cancer

Thank you

Trial Information

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)


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Outcome Description:

to determine the maximum tolerated dose (MTD) and recommended dose of weekly RAD001 in combination with carboplatin and paclitaxel (phase I)

Outcome Time Frame:

weekly

Safety Issue:

Yes

Principal Investigator

Sandrine Faivre

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hopital Beaujon

Authority:

France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:

CDR0000698330

NCT ID:

NCT01333085

Start Date:

October 2009

Completion Date:

May 2013

Related Keywords:

  • Head and Neck Cancer
  • 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
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms

Name

Location