A Study of Carboplatin, Cetuximab and RAD001 in Advanced Head and Neck Cancer

NCT01283334 | Completed Phase 1 Results DMC

• 2 other identifiers: IRB00040298WCI1761-09
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the drug RAD001 in combination with other chemotherapy drugs, Carboplatin and Cetuximab. Because RAD001 has not been used in this combination before, it is not clear which dose will be best when used in combination. The investigators will test the safety of RAD001 in combination with Carboplatin and Cetuximab and see what effects (good and/or bad) it has on your cancer, and find the highest dose of RAD001 that can be given without causing bad side effects. The doses of Carboplatin and Cetuximab will not be varied as both these drugs are considered to be part of the current standard of care for patients with your condition.

Conditions

Head and Neck Neoplasms; Cancer of the Head and Neck

Keywords

Head and Neck Cancer; Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Outcome Measures

Primary Outcomes (1)

• To Measure the Safety and Clinical Effectiveness of the Combination of Carboplatin, Cetuximab and RAD001 in Patients With Advanced (Recurrent or Metastatic) Head and Neck Cancer

  This phase 1 clinical trial used a standard 3 + 3 design. Four dose levels of everolimus were planned to be evaluated, and the standard 3 + 3 design with dose de-escalation was used in the trial. Namely, 3 patients were assigned to starting dose level 1. If no dose-limiting toxicity (DLT) was observed, the trial proceeded to the next dose level, and another cohort of 3 patients was enrolled. If at least 2 of the 3 patients experienced at least 1 DLT, then the dose level decreased; otherwise, if only 1 patient experienced DLT, then 3 more patients were enrolled at the same dose level. If none of the 3 additional patients experienced DLT, the dose was escalated; otherwise, the dose level decreased. Dose reduction continued until a dose level was reached at which 6 patients had been treated and at most 1 DLT was observed.

  Within the first 21 days of therapy

Secondary Outcomes (1)

• Progression-free Survival (PFS)

  The time of PFS was calculated as the time from study enrollment to the disease progression date, death date, or last contact, whichever came first, up to 25 months

Study Arms (1)

A

EXPERIMENTAL

Treatment arm with carboplatin, cetuximab and RAD001

Drug: Carboplatin; Drug: Cetuximab; Drug: RAD001

Interventions

Carboplatin DRUG

Will be given as a 30 minutes intravenous (IV) infusion on days 1, 8, and 15 of each 28 day cycle. The starting dose of carboplatin will be area under the plasma-concentration time curve (AUC) = 2 mg/ml.min. Appropriate dose reductions will be done for toxicity for subsequent cycles.

Also known as: Paraplatin

A

Cetuximab DRUG

Will be given on days 1, 8, 15 and 22 of each 29 day cycle. On week 1, a loading dose of 400 mg/m² will be given. From week 2 onwards, the dose of cetuximab will be 250 mg/m².

Also known as: Erbitux

A

RAD001 DRUG

For phase I, dose escalation will be 2.5 mg, 5 mg, 7.5 mg or 10 mg given orally on a daily basis.

Also known as: Everolimus, Certican

A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have at least one measurable site of disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
• Histologically or cytologically proven squamous cell carcinoma of the head and neck (SCCHN).
• Patients with recurrent, refractory or metastatic squamous cell carcinoma of oral cavity, oropharynx and larynx, hypopharynx or paranasal sinus, and unknown primary SCCHN who failed to respond to, or relapsed from prior chemoradiotherapy for definitive treatment of disease.
• Evaluable locoregional and/or metastatic disease according to RECIST criteria (see Section 6) that is not appropriate for treatment by primary surgical resection or radiotherapy.
• Patients may not have had prior chemotherapy for recurrent or metastatic disease.
• Patients must not be candidates for curative therapy.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Life expectancy of ≥ 4 months.
• Adequate bone marrow, liver and renal function as assessed by the following:
• Hemoglobin ≥ 9.0/dl
• Absolute-neutrophil count (ANC ) ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement)

You may not qualify if:

• History of prior malignancy within the past 5 years except for curatively treated basal cell carcinoma and squamous cell carcinoma of the skin, cervical intraepithelial neoplasia (CIN) or localized prostate cancer with a current prostate-specific antigen (PSA) \< 1.0 mg/dL on 2 successive evaluations at least 3 months apart, with the most recent evaluation within 4 weeks of study entry.
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
• Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.).
• Prior treatment with any investigational drug within the preceding 4 weeks.
• Any unresolved toxicity (except alopecia) greater than NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 grade 2 from prior systemic anticancer therapy.
• Patients who have received prior treatment with a mammalian target of rapamycin (mTOR) inhibitor (sirolimus, temsirolimus, everolimus).
• Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients, or to cetuximab.
• Prior therapy with Cetuximab will be allowed provided it was part of definitive therapy and not part of treatment for recurrent or metastatic disease.
• Prior severe infusion reaction to a monoclonal antibody.
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
• Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period.
• Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study.
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Symptomatic congestive heart failure of New York heart Association Class III or IV
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease

Sponsors & Collaborators

• Emory University: lead
• Novartis: collaborator

Study Sites (1)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Saba NF, Hurwitz SJ, Magliocca K, Kim S, Owonikoko TK, Harvey D, Ramalingam SS, Chen Z, Rogerio J, Mendel J, Kono SA, Lewis C, Chen AY, Higgins K, El-Deiry M, Wadsworth T, Beitler JJ, Shin DM, Sun SY, Khuri FR. Phase 1 and pharmacokinetic study of everolimus in combination with cetuximab and carboplatin for recurrent/metastatic squamous cell carcinoma of the head and neck. Cancer. 2014 Dec 15;120(24):3940-51. doi: 10.1002/cncr.28965. Epub 2014 Aug 7.

  PMID: 25103371 RESULT

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Carboplatin; Cetuximab; Everolimus

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sirolimus; Macrolides; Lactones

Limitations and Caveats

Limitations of this analysis include the small sample size in this phase 1b study, a patient population with mixed primary sites of disease, and variable doses of everolimus.

Results Point of Contact

• Title: Nabil F. Saba, MD
• Organization: Emory University

nfsaba@emory.edu

404-778-1900

Study Officials

• Nabil F. Saba, MD

  Emory University Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: January 24, 2011
• First Posted: January 25, 2011
• Study Start: January 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2014
• Last Updated: December 4, 2014
• Results First Posted: December 4, 2014

Record last verified: 2014-11

Locations

US (1)