RAD001 With Weekly Cisplatin and Radiation Therapy in Patients With Locally Advanced Head and Neck Cancer

Sponsor

Dana-Farber Cancer Institute (Other)

Overall Status

Terminated

CT.gov ID

NCT01058408

Collaborator

Brigham and Women's Hospital (Other), Novartis (Industry)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

RAD001 is approved by the U.S Food and Drug Administration (FDA) to treat advanced kidney cancer. This drug has also been used in other research studies to evaluate its effectiveness in other cancers. Information from these research studies suggests that RAD001 may help to decrease the growth and development of tumor cells by reducing the blood supply that tumors need to grow. In this research study, we are trying to determine the safety of RAD001 when given to people with locally advanced head and neck cancer in combination with cisplatin and radiation. We are also looking for the highest dose of RAD001 that can be given to people safely.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Radiation: Intensity modulated radiotherapy Drug: RAD001 Drug: cisplatin	Phase 1

Detailed Description

Most patients receiving treatment for head and neck cancer will develop difficulty swallowing food and drinking liquids during the course of therapy. For this reason, it will be recommended that a PEG (percutaneous endoscopic gastrostomy) tube be placed in the participants stomach prior to undergoing the study regimen. This is to help maintain weight and nutritional health.
Since we are looking for highest dose of the study drug that can be administered safely without severe or unmanageable side effects, not everyone who participates will receive the same dose of RAD001 or cisplatin.
The study regimen will last for seven weeks. During each week of study participation the following will occur: Radiation will be administered each weekday (5 days per week). Cisplatin will be given intravenously at the start of each week. RAD001 will be given to the participant to take at home. Participants will take the study drug once a day in the morning starting on day 1.
A history and physical exam will be performed weekly while participant's are receiving radiation treatment. Blood tests for routine laboratory testing will be performed weekly.
Each month for the first two months after participants finish radiation therapy and stop taking RAD001 and cisplatin, they will have a physical ezam, a neurologic exam, and blood tests. X-rays, a CT, MRI and/or PET scans will also be performed a the two month visit. After the first two months, follow-up will continue every 1-2 months for the first year. Additionally, every 6 months for the first two years, follow-up visits will include an assessment of speech and swallowing functions along with X-rays, CT, MRI and/or PET scans.

Study Design

Study Type:

Interventional

Actual Enrollment :

3 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Trial Using RAD001 With Weekly Cisplatin and Radiation Therapy in Patients With Locally Advanced Head and Neck Cancer

Study Start Date :

Feb 1, 2010

Actual Primary Completion Date :

Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rad001 with cisplatin	Radiation: Intensity modulated radiotherapy Administered daily 5 days per week Other Names: IMRT Drug: RAD001 Taken orally once a day Drug: cisplatin Administered intravenously once a week

Arm

Intervention/Treatment

Experimental: Rad001 with cisplatin

Radiation: Intensity modulated radiotherapy

Administered daily 5 days per week

Other Names:

IMRT

Drug: RAD001

Taken orally once a day

Drug: cisplatin

Administered intravenously once a week

Outcome Measures

Primary Outcome Measures

To evaluate the maximum tolerated dose (MTD) and safety of the RAD001 in combination with weekly cisplatin and radiation in patients with locally advanced HNSCC. [2 years]

Secondary Outcome Measures

Obtain preliminary results on efficacy of the RAD001, cisplatin and radiation therapy combination in patients with locally advanced HNSCC. [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with stage III/IV, locally advanced, biopsy proven squamous cell cancer of the head and neck who are planned to undergo chemoradiation as their primary treatment with curative intent. Patients with oropharynx, hypopharynx, larynx primaries, nasopharynx as well as those with documented SCC of the cervical lymph nodes, with unknown primaries, are eligible.
Patients must have at least evaluable disease and one measurable site of disease according to RECIST criteria is desirable.
18 years of age or older
Minimum of two weeks since any major surgery
WHO performance status of 2 or less
Adequate bone marrow, liver, and renal function as outlined in the protocol

Exclusion Criteria:

Presence of distant metastatic disease
Prior chemotherapy
Prior radiation to the head and neck or adjacent anatomical site
Chronic treatment with systemic steroids or another immunosuppressive agent
Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
Other malignancies within the past 3 years except for adequately treated carcinoma of the thyroid, cervix or basal or squamous cell carcinomas of the skin
Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
Uncontrolled diabetes mellitus
A known history of HIV seropositivity
Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001
Patients with an active, bleeding diathesis or on oral anti-vitamin K medication
Women who are pregnant or breastfeeding, or women/men able to conceive and unwilling to practice an effective method of birth control
Patients who have received prior treatment with an mTOR inhibitor
Patients with a known hypersensitivity to RAD001 or other rapamycins or to its excipients