RAD001 in Combination With Cetuximab and Cisplatin in Recurrent and Metastatic SCCHN

NCT01009346 | Terminated Phase 1 Results DMC

• 2 other identifiers: J0916NA_00023951
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

1.Phase I: To estimate the Maximum Tolerated Dose (MTD) of RAD001 in combination with cetuximab and cisplatin for treatment of metastatic squamous cell cancer of the head and neck (SCCHN). Secondary Objectives 1.To assess the toxicity of RAD001 in combination with weekly cetuximab and cisplatin on days 1 and 8 of each 28 day cycle in patients with recurrent or metastatic SCCHN,

Conditions

Head and Neck Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of RAD001 in Combination With Cetuximab and Cisplatin.

  MTD will be defined as a) the dose of RAD001 producing DLT in 0-1 out of 6 patients, or b) the dose level below the dose which produced DLT in \<2 out of 6 patients, or c) the dose of 10mg po qd with less than 33% rate of DLT

  6 months

Secondary Outcomes (1)

• Progression Free Survival (PFS) of RAD001 in Combination With Weekly Cetuximab and Cisplatin.

  2 years

Study Arms (1)

RAD001

EXPERIMENTAL

Daily RAD001 in combination with weekly cetuximab and cisplatin/ carboplatin on Day 1, 8 of each 28 day cycle.

Drug: RAD001; Drug: Cetuximab; Drug: Cisplatin; Drug: Carboplatin

Interventions

RAD001 DRUG

Dose Level -1 2.5mg/day Dose Level 1 5mg/day\* Dose Level 2 10mg/day MTD RAD001

Also known as: Everolimus

RAD001

Cetuximab DRUG

250mg/m2/week

Also known as: Erbitux

RAD001

Cisplatin DRUG

40mg/m2 Day 1, 8 every 28 days

Also known as: cisplatinum, CDDP, cis-diamminedichloroplatinum(II)

RAD001

Carboplatin DRUG

Carboplatin will be administered on Day1 and Day 8 of each 28 day cycle to a target AUC of 3 over 30 minutes. Carboplatin will be dosed using the Calvert formula: Total dose (mg) = (target AUC) x (glomerular filtration rate + 25) Creatinine clearance will be used to estimate the GFR. The Cockgroft-Gault formula will be used to estimate the creatinine clearance.

Also known as: cis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II)

RAD001

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 histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the head and neck, with recurrent or metastatic disease.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan. See Section 11 for the evaluation of measurable disease.
• Patients must have had no prior monoclonal antibodies or small molecule tyrosine-kinase inhibitors for the treatment of recurrent or metastatic SCCHN. In addition, no prior chemotherapy for the treatment of recurrent or metastatic SCCHN is allowed.
• If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation. Patients must be greater than or equal to 12 weeks from completion of prior curative intent therapy including surgery, radiation, or systemic anticancer therapy. If palliative radiation therapy is given for recurrent or metastatic disease, patients must be greater than or equal to four weeks from treatment.
• No concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. Patients with prior history of malignancies must be disease free for greater than or equal to two years.
• Age \>18 years.
• Life expectancy of greater than 4.5 months.
• ECOG performance status \<2 (Karnofsky \>60%; see Appendix A).
• Patients must have normal organ and marrow function as defined below:
• leukocytes \>3,000/mcL
• absolute neutrophil count \>1,500/mcL
• platelets \>100,000/mcL
• total bilirubin less than or equal to 1.5 X institutional upper limit of normal or within normal institutional limits. or
• AST(SGOT)/ALT(SGPT) \<3.0 X institutional upper limit of normal - creatinine within normal institutional limits OR
• creatinine clearance \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal 3.1.8

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients may not be receiving any other investigational agents.
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to RAD001 or other agents used in the study.
• Patients receiving any medications or substances that are inhibitors or inducers of the isoenzyme CYP3A are ineligible. Lists including medications and substances known or with the potential to interact with the CYP3A isoenzymes are provided in the appendix.
• Patients receiving chronic treatment with systemic steroids or other immunosuppressive agents are ineligible.
• Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycin (sirolimus, temsirolimus) or its excipients.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g. ulcerative disease; uncontrolled nausea, vomiting, or diarrhea; malabsorption syndrome or small bowel resection).
• Patients with active bleeding diathesis or patients on oral anti-vitamin K agent (excluding low dose warfarin).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, severely impaired lung function or psychiatric illness/social situations that would limit compliance with study requirements Severely impaired lung function is defined as spirometry and DLCO that is 50% of the normal predicted value and /or O2 saturation that is 88% or less on room air.
• Pregnant women are excluded from this study because RAD001 is a mTOR inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with RAD001, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with RAD001. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Everolimus; Cetuximab; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed

Results Point of Contact

• Title: Ranee Mehra, MD
• Organization: Johns Hopkins

rmehra1@jhmi.edu

Study Officials

• Shanthi Marur, MD

  Johns Hopkins SKCCC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2009
• First Posted: November 6, 2009
• Study Start: October 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: July 17, 2018
• Results First Posted: June 9, 2014

Record last verified: 2018-06

Locations

US (1)