Everolimus, Carboplatin, and Paclitaxel in Locally Advanced Head and Neck Cancer That Cannot Be Removed by Surgery (CAPRA)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
ClinicalTrials.gov Identifier:
NCT01333085
First received: April 8, 2011
Last updated: March 12, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Drug: carboplatin
Drug: RAD001
Drug: paclitaxel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR):

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: weekly ] [ Designated as safety issue: Yes ]
    to determine the maximum tolerated dose (MTD) and recommended dose of weekly RAD001 in combination with carboplatin and paclitaxel (phase I)

  • objective response rate [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    To access the objective response rate of the combination RAD001-carboplatin-Paclitaxel according the the RECIST criteria, after 9 weekly cycles (phase II)


Enrollment: 49
Study Start Date: October 2009
Estimated Study Completion Date: May 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RAD001-paclitaxel-carboplatin
RAD001: 20,30 or 50 mg PO 9 weekly cycles Paclitaxel: 60 mg/m²IV, in 1 hour, 9 weekly cycles Carboplatin AUC2 IV in 1 hour,9 weekly cycles
Drug: carboplatin Drug: RAD001
Other Name: everolimus
Drug: paclitaxel

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01333085

Locations
France
Hopital Beaujon
Clichy, France, 92110
Centre Léon Berard
Lyon, France, 69000
Hôpital Privé Saint Joseph
Paris, France, 75014
Institut Curie
Paris, France, 75005
Institut Claudius Regaud
Toulouse, France, 31052
Sponsors and Collaborators
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
Investigators
Principal Investigator: Sandrine Faivre Hopital Beaujon
  More Information

Additional Information:
No publications provided

Responsible Party: Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
ClinicalTrials.gov Identifier: NCT01333085     History of Changes
Other Study ID Numbers: CDR0000698330, FRE-GERCOR-CAPRA, FRE-GERCOR-O08-1, EU-21109, EUDRACT-2008-005702-39
Study First Received: April 8, 2011
Last Updated: March 12, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
FRANCE: Committee of Protection of the Persons

Keywords provided by Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR):
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

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Paclitaxel
Carboplatin
Sirolimus
Everolimus
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2014