Trial of RAD001 and Erlotinib With Recurrent Head and Neck Squamous Cell Carcinoma

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00942734
• Collaborator: Novartis (Industry), OSI Pharmaceuticals (Industry)
• Enrollment: 49
• Location: 1
• Arm: 1
• Duration (Months): 64
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if RAD001 in combination with Tarceva (erlotinib hydrochloride) can help to control head and neck squamous cell cancer (HNSCC). The safety of this drug combination will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Head And Neck Cancer	Drug: Erlotinib; Drug: RAD001	Phase 2

Detailed Description

The Study Drugs:

RAD001 is designed to stop cancer cells from multiplying. It may also stop the growth of new blood vessels that help tumor growth, and this may cause the tumor cells to die.

Erlotinib hydrochloride is designed to block the activity of a protein found on the surface of many tumor cells that may control tumor growth and survival. This may stop tumors from growing.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take 1 RAD001 tablet and 1 erlotinib hydrochloride tablet every day of each 28 day study "cycle".

Both drugs should be taken at the same time, by mouth, with a cup (8 ounces) of water. You should take the drugs at least 1 hour before or 2 hours after eating. You should take the study drugs at around the same time each day. Your eating habits around the time you take the drugs should stay the same while you are on study. lf you vomit, you should not take another tablet until your next scheduled dose.

Tell your doctor if you have any side effects, as your dose(s) of study drug(s) may be lowered or stopped for a few days. You may be given drugs to help reduce the risk of side effects.

Study Visits:

On Day 1 (+/- 3 days) of each cycle, the following tests and procedures will be performed:

• You will have a complete physical exam, including measurement of your weight and vital signs.

• You will be asked about any drugs you may be taking and any side effects you may be having.

• Your performance status will be recorded.

• Blood (about 3 teaspoons) will be drawn for routine tests. If your doctor thinks it is needed, you may have to have these blood tests more often.

On Day 1 (+/- 3 days) of every evenly numbered cycle (Cycles 2, 4, 6, and so on), you will have a CT scan or MRI scan to check the status of the disease.

Length of Study:

You may continue to take the study drugs for as long as you are benefitting. You will be taken off study if the disease gets worse or if you have intolerable side effects.

End-of-Study Visit:

When you go off study for any reason, you will have an end-of-study visit. The following tests and procedures will be performed:

• Your medical history will be recorded.

• You will have a complete physical exam, including measurement of your weight and vital signs.

• You will be asked about any drugs you may be taking and any side effects you may be having.

• Your performance status will be recorded.

• Blood (about 3 teaspoons) will be drawn for routine tests.

• You will have a CT scan or MRI scan to check the status of the disease.

Follow-Up:

You will be called within 30 days after the end-of-study visit and asked how you are doing and about any possible side effects that you may have had. The call should take about 5 minutes.

This is an investigational study. RAD001 is FDA approved and commercially available for the treatment of certain types of breast cancer. Erlotinib hydrochloride is FDA approved and commercially available for the treatment of advanced non-small cell lung carcinoma (NSCLC) and advanced pancreatic cancer. The use of this drug combination for the treatment of HNSCC is investigational.

Up to 35 patients will take part in this study. All will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Clinical Trial of the Combination of RAD001 and Erlotinib in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RAD001 + Erlotinib RAD001 1 tablet (5 mg) by mouth every day of each 28 day study cycle. Erlotinib one tablet (150 mg) by mouth every day of each 28 day study cycle.	Drug: Erlotinib; One tablet (150 mg) by mouth every day of each 28 day study cycle.; Other Names: OSI-774 Tarceva ; Drug: RAD001; 1 tablet (5 mg) by mouth every day of each 28 day study cycle.; Other Names: Everolimus

Outcome Measures

Primary Outcome Measures

1. 12-Week Progression-Free Survival (PFS) [12 weeks]

   Tumor assessments performed by Computed Tomography (CT) scan or Magnetic Resonance Imaging (MRI) after 4 weeks, 12 weeks, then every 8 weeks thereafter. Participants who received at least one dose of RAD001+erlotinib and who die before 12 weeks, counted as having progressive disease. Response Evaluation Criteria in Solid Tumors (RECIST) defined as Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >30% decrease in sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Progression-free survival defined as stable disease or better. Progressive Disease (PD): >20% increase in sum of LD of target lesions, taking as reference smallest sum LD recorded since treatment started or appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum LD since treatment started.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Histologically or cytologically confirmed squamous cell carcinoma of the head and neck

2. Patients that have failed one platinum-containing chemotherapy regimen with or without EGFR inhibitor and/or epidermal growth factor receptor (EGFR) inhibitor as systemic therapy for recurrent/metastatic disease. Prior investigational therapy (with the exclusion of mammilian target of rapamycin (mTOR) inhibitor) allowed but at least 4 weeks must have elapsed with recovery from all toxicities

3. Patients who had prior induction or concurrent chemotherapy delivered as part of their primary treatment are eligible as long as they have completed primary therapy at least 6 months prior to study entry.

4. 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

5. Age >/= 18 years

6. Minimum of two weeks since any major surgery or completion of radiation. Note: Patients may have received prior radiation therapy to tumor sites that will not be assessed for response, unless there is evidence of progression.

7. Completion of all prior systemic anticancer therapy for the treatment of recurrent/metastatic disease (adequately recovered from the acute toxicities of any prior therapy) at least 4 weeks prior to study entry

8. Eastern Cooperative Oncology Group (ECOG) performance status </= 2

9. Laboratory Values (within 14 days prior to administration of study drugs): Adequate bone marrow function as shown by: absolute neutrophil count (ANC) >/= 1.5 * 10^{9/L, Platelets >/= 100 * 10}9/L, Hgb > 10 g/dL; Adequate liver function as shown by: serum bilirubin </=1.5 * upper limit of normal (ULN), and serum transaminases activity </= 3

• ULN. With the exception of serum transaminases (< 5 * ULN) if the patient has liver metastases

1. Continued from Inclusion # 9: Fasting serum cholesterol </= 300 mg/dL OR </= 7.75 mmol/L AND fasting triglycerides </= 2.5 * ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication

2. Signed informed consent

Exclusion Criteria:

1. Prior treatment with any investigational drug within the preceding 4 weeks, concomitant chemotherapy, hormonal therapy, radiotherapy or immunotherapy, or therapy with agents otherwise used in treatment of cancer (for example, methotrexate for rheumatoid arthritis)

2. Chronic treatment with systemic steroids or another immunosuppressive agent. Steroids will not be allowed and should be discontinued 24 hours prior to initiation of treatment on protocol. An exception for replacement steroids prescribed for adrenal insufficiency will be allowed.

3. Patients should not receive immunization with attenuated live vaccines during study period or within one week of study entry

4. Patients with metastatic disease to the brain, unless treated and controlled and the patient is off steroids and/or antiepileptics for at least 3 weeks.

5. Other malignancies within the past 2 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.

6. Patients with active skin, mucosa, ocular or gastrointestinal disorders grade > 1

7. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction, </= 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia

8. Continued from Exclusion #7: severely impaired lung function; uncontrolled diabetes as defined by fasting serum glucose >1.5x ULN; any active (acute or chronic) or uncontrolled infection/ disorders.; nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy; liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis

9. A known history of HIV or AIDS-related illness or previous seropositivity for the virus

10. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study agents (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).

11. Patients with any condition which impairs the ability to swallow study agent intact

12. Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumarin)

13. Women who are pregnant or breast feeding, or women/men able to conceive and unwilling to practice an effective method of birth control. (Women of childbearing potential (WOCP) must have a negative urine or serum pregnancy test within 7 days prior to administration of study drugs). WOCP: A female of child bearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

14. (Continued from Exclusion # 13) Females must either commit to abstinence from heterosexual intercourse or use a barrier method of contraception. Oral, implantable, and injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Males must either commit to abstinence from heterosexual intercourse or use a barrier method of contraception.

15. Lack of resolution of all toxic manifestations of prior chemotherapy biologic therapy or radiation therapy.

16. Patients who have received prior treatment with an mTor inhibitor.

17. Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients

18. Patients with psychiatric illness or confusional status that may impair the patient's understanding of the informed consent

19. Patients unwilling to or unable to comply with the protocol

20. Patients with any condition which impairs the ability to swallow study agent intact

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Novartis
• OSI Pharmaceuticals

Investigators

• Principal Investigator: Vali Papadimitrakopoulou, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00942734
• Other Study ID Numbers: 2008-0567; NCI-2012-01643
• First Posted: Jul 21, 2009
• Last Update Posted: Feb 4, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by M.D. Anderson Cancer Center: Head and Neck; Squamous Cell Carcinoma; RAD001; Erlotinib; Everolimus; OSI-774; Tarceva
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Everolimus; Erlotinib Hydrochloride

Study Results

Participant Flow

Recruitment Details	Recruitment Period: July 17, 2009 to February 08, 2013. Recruitment was done in various medical clinics in the United States.
Pre-assignment Detail	Of the forty-nine participants registered, six participants were ineligible and not treated.

Arm/Group Title	RAD001 + Erlotinib
Arm/Group Description	RAD001 5 mg orally and Erlotinib 150 mg orally every day of each 28 day study cycle.
Period Title: Overall Study
STARTED	43
COMPLETED	35
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	RAD001 + Erlotinib
Arm/Group Description	RAD001 5 mg orally and Erlotinib 150 mg orally every day of each 28 day study cycle.
Overall Participants	43
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	8 18.6%
Male	35 81.4%
Region of Enrollment (participants) [Number]
United States	43 100%

Outcome Measures

1. Primary Outcome

Title	12-Week Progression-Free Survival (PFS)
Description	Tumor assessments performed by Computed Tomography (CT) scan or Magnetic Resonance Imaging (MRI) after 4 weeks, 12 weeks, then every 8 weeks thereafter. Participants who received at least one dose of RAD001+erlotinib and who die before 12 weeks, counted as having progressive disease. Response Evaluation Criteria in Solid Tumors (RECIST) defined as Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >30% decrease in sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Progression-free survival defined as stable disease or better. Progressive Disease (PD): >20% increase in sum of LD of target lesions, taking as reference smallest sum LD recorded since treatment started or appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum LD since treatment started.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Eight participants were not evaluable.

Arm/Group Title	RAD001 + Erlotinib
Arm/Group Description	RAD001 5 mg orally and Erlotinib 150 mg orally every day of each 28 day study cycle.
Measure Participants	35
Number [Percentage of Participants]	48.57 113%

Adverse Events

Time Frame	Adverse events collected through 12 weeks of treatment (± 3 days).
Arm/Group Title	RAD001 + Erlotinib
Arm/Group Description	RAD001 5 mg orally and Erlotinib 150 mg orally every day of each 28 day study cycle.
All Cause Mortality
	RAD001 + Erlotinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	RAD001 + Erlotinib
	Affected / at Risk (%)	# Events
Total	1/43 (2.3%)
Metabolism and nutrition disorders
hypercalcaemia	1/43 (2.3%)
Other (Not Including Serious) Adverse Events
	RAD001 + Erlotinib
	Affected / at Risk (%)	# Events
Total	43/43 (100%)
Blood and lymphatic system disorders
HEMOGLOBIN	5/43 (11.6%)	5
LEUKOCYTES	2/43 (4.7%)	2
PLATELETS LEVEL	5/43 (11.6%)	5
Gastrointestinal disorders
ANOREXIA	3/43 (7%)	3
DIARRHEA	18/43 (41.9%)	18
DYSPHAGIA	2/43 (4.7%)	2
MUCOSITIS	18/43 (41.9%)	18
NAUSEA	9/43 (20.9%)	9
PAIN (ORAL CAVITY)	2/43 (4.7%)	2
VOMITING	5/43 (11.6%)	5
General disorders
DIZZINESS	2/43 (4.7%)	2
EDEMA: HEAD AND NECK	9/43 (20.9%)	9
EDEMA: LIMB	2/43 (4.7%)	2
FATIGUE	18/43 (41.9%)	18
WEIGHT LOSS	11/43 (25.6%)	11
Investigations
FEVER WITHOUT NEUTROPINIA	2/43 (4.7%)	2
Metabolism and nutrition disorders
CHOLESTEROL	2/43 (4.7%)	2
HYPERGLYCEMIA	2/43 (4.7%)	2
HYPERTRIGLYCERIDEMIA	3/43 (7%)	3
HYPOKALEMIA	2/43 (4.7%)	2
Respiratory, thoracic and mediastinal disorders
DYSPNEA	2/43 (4.7%)	2
Skin and subcutaneous tissue disorders
ACNE	27/43 (62.8%)	27
DERMATOLOGY/SKIN	5/43 (11.6%)	5
HAND-FOOT SYNDROME	2/43 (4.7%)	2
NAIL CHANGES	4/43 (9.3%)	4
PRURITUS	4/43 (9.3%)	4
RASH/DESQUAMATION	5/43 (11.6%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.