Ridaforolimus With Cetuximab: Adv Non-Small Cell Lung, Colorectal, Head & Neck Cancer

• Sponsor: Angela Taber MD (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01212627
• Collaborator: Rhode Island Hospital (Other), The Miriam Hospital (Other), Memorial Hospital of Rhode Island (Other), Roger Williams Medical Center (Other)
• Enrollment: 12
• Locations: 2
• Arm: 1
• Duration (Months): 31
• Patients Per Site: 6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The main purpose of this study is to evaluate the best dose, safety and side effects of ridaforolimus when given with cetuximab for patients with head and neck, lung and colon cancer that has progressed after initial therapy. A second purpose of this study is to gain preliminary information on whether the combination of ridaforolimus and cetuximab is helpful in treating patients with advanced head and neck cancer

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: Ridaforolimus	Phase 1

Detailed Description

Patients with advanced NSCLC, colorectal cancer, and head and neck cancer that progressed after at least 1 prior regimen for metastatic disease were eligible. Wild-type K-ras was required in colon cancer. All patients received cetuximab 400 mg/m2 week 1 followed by 250 mg/m2/week. Four dose levels of ridaforolimus were planned: 10mg, 20mg, 30mg, and 40mg daily, 5 days each week, on a 28-day cycle.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: BrUOG- Phase 1-233: A Phase I Study of Ridaforolimus With Cetuximab for Patients With Advanced Head and Neck Cancer, Non-Small Cell Lung Cancer and Colon Cancer
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ridaforolimus Ridaforolimus: 20mg Daily, 5 days each week, on a 28 day cycle until progression	Drug: Ridaforolimus; Ridaforolimus 20 Daily, 5 days each week, (Mon-Fri) on a 28 day cycle; Other Names: deforolimus

Outcome Measures

Primary Outcome Measures

1. Determine Maximum Tolerated Dose (MTD) of Ridaforolimus With Given With Cetuximab [1 year]

   the first testing will occur once the first 3 patients are enrolled and have received 1 cycle DLT's will be evaluated- if everything is ok then the next level of medication will begin Weekly Ridaforolimus Dose Level 1 20 mg/day Dose Level 2 30 mg/day Dose Level 3 40 mg/day

Secondary Outcome Measures

1. Check the Tolerability, and Maximum Tolerated Dose (MTD) of Several Dosing Schedules of Oral Ridaforolimus. [1 year]

   the first testing will occur once the first 3 patients are enrolled and have received 1 cycle DLT's will be evaluated- if everything is ok then the next level of medication will begin

Eligibility Criteria

Criteria

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

Inclusion Criteria

• Histologically or cytologically advanced head and neck cancer, NSCLC or colorectal cancer (wild-type KRAS) in whom there is no curable option and have progressed after at least one regimen for advanced disease. Once the final dose level has been determined, only patients with advanced lung cancer who fail at least one line of chemotherapy will be eligible to be accrued to the 13 patient expanded cohort. *** As of July 7, 2011 the final dosing level has been determined and the next cohort of patients with advanced lung cancer will be enrolled**

• Patient has measurable disease by protocol-specific RECIST criteria.

• A minimum of 4 weeks has elapsed between prior chemotherapy and day 1 of study treatment.

• A minimum of 14 days has elapsed since prior kinase inhibitor therapy or radiotherapy, and a minimum of 4 weeks has elapsed since prior bevacizumab.

• No prior exposure to an mTOR inhibitor. Prior cetuximab exposure is allowed.

• ECOG performance status 0-1

• Required initial lab values: Hemoglobin ≥9.0 g/dL, absolute neutrophil count ≥1,500/mm3, platelet count ≥100,000/mm3, total bilirubin ≤1.5 times the upper limit of normal, AST or ALT <3 times the upper limit of normal, serum albumin ≥2.5 g/dL, serum cholesterol ≤350 mg/dL, triglycerides ≤400 mg/dL, creatinine <1.5 times the upper limit of normal, or a calculated creatinine clearance ≥50 ml/min.

• Age ≥18 years

• Those of child-bearing potential must agree to use of effective method of contraception

• Patients must have the ability to understand and give written informed consent

Exclusion criteria:

• Patient is known to have active brain metastases. Patients with previously treated brain metastases that are stable for >3months are eligible if a current brain MRI (within 28 days of day 1 of study treatment) shows no edema or evidence of progression compared to a prior study at least 3 months ago.

• Patient is currently participating or has participated in a study with an investigational anticancer treatment or device within 30 days or 5 half lives of the investigational compound (whichever is greater) of initial dosing with study drug.

• Patient has previously received rapamycin or rapamycin analogs, including ridaforolimus, everolimus, or temsirolimus.

• Patient is receiving corticosteroids administered at doses greater than those used for normal replacement therapy.

• Patient has a history of prior invasive malignancy except for basal cell carcinoma of the skin within the past two years or who is deemed at low risk for recurrence by his treating physician.

• Patient has known severe hypersensitivity to macrolide antibiotics (ie: clarithromycin, erythromycin, or azythromycin).

• Patient has NYHA Class III or IV congestive heart failure or any other significant history of cardiac disease including: myocardial infarction within the last 6 months; ventricular arrhythmia or acute congestive heart failure within the last 3 months; uncontrolled angina or uncontrolled hypertension.

• Patient is known to be HIV positive or has a known history of Hepatitis B or C.

• Patient has a psychiatric disorder that would interfere with cooperation with the requirements of the trial, is a regular user of illicit drugs (including "recreational use"), or has a recent history (within the last year) of drug or alcohol dependence.

• Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the study.

• Patient has an active infection requiring intravenous antibiotics.

• Patient has a requirement for concurrent treatment with medications that are strong inducers or inhibitors of cytochrome P450 (CYP3A) (see Appendix). Patients should discontinue these medications for at least 2 weeks prior to the first dose of ridaforolimus. Concomitant medications that are metabolized by CYP3A are allowed (e.g., simvastatin or atorvastatin)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	memorial Hospital of Rhode island	Pawtucket	Rhode Island	United States	02860
2	The Miriam Hospital	Providence	Rhode Island	United States	02906

Sponsors and Collaborators

• Angela Taber MD
• Rhode Island Hospital
• The Miriam Hospital
• Memorial Hospital of Rhode Island
• Roger Williams Medical Center

Investigators

• Principal Investigator: Angela Plette, MD, Lifespan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Angela Taber MD, Principle Investigator, Brown University
• ClinicalTrials.gov Identifier: NCT01212627
• Other Study ID Numbers: BrUOG-Phase 1-233
• First Posted: Sep 30, 2010
• Last Update Posted: Feb 16, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by Angela Taber MD, Principle Investigator, Brown University: Non-Small Cell Lung Cancer
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Study Results

Participant Flow

Arm/Group Title	Ridaforolimus,
Arm/Group Description	Ridaforolimus: 20mg Daily, 5 days each week, on a 28 day cycle until progression Ridaforolimus: Ridaforolimus 20 Daily, 5 days each week, (Mon-Fri) on a 28 day cycle Ridaforolimus
Period Title: Overall Study
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Ridaforolimus,
Arm/Group Description	Ridaforolimus: 20mg Daily, 5 days each week, on a 28 day cycle until progression Ridaforolimus: Ridaforolimus 20 Daily, 5 days each week, (Mon-Fri) on a 28 day cycle Ridaforolimus
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 75%
>=65 years	3 25%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	57.8
Sex: Female, Male (Count of Participants)
Female	4 33.3%
Male	8 66.7%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Determine Maximum Tolerated Dose (MTD) of Ridaforolimus With Given With Cetuximab
Description	the first testing will occur once the first 3 patients are enrolled and have received 1 cycle DLT's will be evaluated- if everything is ok then the next level of medication will begin Weekly Ridaforolimus Dose Level 1 20 mg/day Dose Level 2 30 mg/day Dose Level 3 40 mg/day
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ridaforolimus,
Arm/Group Description	Ridaforolimus: 20mg Daily, 5 days each week, on a 28 day cycle until progression Ridaforolimus: Ridaforolimus 20 Daily, 5 days each week, (Mon-Fri) on a 28 day cycle Ridaforolimus
Measure Participants	12
Number [mg/day]	20

2. Secondary Outcome

Title	Check the Tolerability, and Maximum Tolerated Dose (MTD) of Several Dosing Schedules of Oral Ridaforolimus.
Description	the first testing will occur once the first 3 patients are enrolled and have received 1 cycle DLT's will be evaluated- if everything is ok then the next level of medication will begin
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Baseline, treatment, 30 days post last dose of drug
Arm/Group Title	Ridaforolimus,
Arm/Group Description	Ridaforolimus: 20mg Daily, 5 days each week, on a 28 day cycle until progression Ridaforolimus: Ridaforolimus 20 Daily, 5 days each week, (Mon-Fri) on a 28 day cycle Ridaforolimus
All Cause Mortality
	Ridaforolimus,
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ridaforolimus,
	Affected / at Risk (%)	# Events
Total	4/12 (33.3%)
Investigations
acute renal failure	1/12 (8.3%)	1
Anemia	1/12 (8.3%)	1
aspiration	1/12 (8.3%)	1
ejection fraction	1/12 (8.3%)	1
Hypokalemia	1/12 (8.3%)	1
pericardial effusion	1/12 (8.3%)	1
Pleural Effusion	1/12 (8.3%)	1
pneumonia	1/12 (8.3%)	1
Respiratory Failure	1/12 (8.3%)	1
Shortness of Breath/dyspnea	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	Ridaforolimus,
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Investigations
acne	2/12 (16.7%)	2
Alk phos	3/12 (25%)	3
Anemia	10/12 (83.3%)	10
Anorexia	3/12 (25%)	3
change in taste	2/12 (16.7%)	2
Constipation	3/12 (25%)	3
cough	4/12 (33.3%)	4
Dehydration	2/12 (16.7%)	2
despression	1/12 (8.3%)	1
Diarrhea	2/12 (16.7%)	2
Dry skin/pruritis/cracked skin	8/12 (66.7%)	8
dysphagia	1/12 (8.3%)	1
edema	2/12 (16.7%)	2
Epistaxis	2/12 (16.7%)	2
Fatigue	7/12 (58.3%)	7
Facial Hair growth	1/12 (8.3%)	1
headache	2/12 (16.7%)	2
hiccups	1/12 (8.3%)	1
Hyperbilirubinemia	1/12 (8.3%)	1
hypercholesterolemia	5/12 (41.7%)	5
hypersensitivity reaction	2/12 (16.7%)	2
hypoalbuminemia	8/12 (66.7%)	8
Hyponatremia	6/12 (50%)	6
hypocalcemia	6/12 (50%)	6
hypoglycemia	3/12 (25%)	3
Hypokalemia	4/12 (33.3%)	4
Hypomagnesemia	6/12 (50%)	6
Hypotension	2/12 (16.7%)	2
Increased phosp	2/12 (16.7%)	2
Increased PT/INR	4/12 (33.3%)	4
infection	5/12 (41.7%)	5
Ingrown nail- toe	1/12 (8.3%)	1
Lipase	1/12 (8.3%)	1
LFTs	3/12 (25%)	3
Lymphopenia	5/12 (41.7%)	5
Light headedness/dizzy	1/12 (8.3%)	1
Mucositis	7/12 (58.3%)	7
nail changes	1/12 (8.3%)	1
Nausea	7/12 (58.3%)	7
Neuropathy	5/12 (41.7%)	5
Pain-localized	6/12 (50%)	6
Pain-general	1/12 (8.3%)	1
Pain-chest	1/12 (8.3%)	1
Pink eyelid	1/12 (8.3%)	1
Pleural Effusion	1/12 (8.3%)	1
Post nasal drip	1/12 (8.3%)	1
Rash	8/12 (66.7%)	8
Shortness of Breath/dyspnea	3/12 (25%)	3
sore throat	1/12 (8.3%)	1
Thrombocytopenia	4/12 (33.3%)	4
TSH	1/12 (8.3%)	1
Thrush	1/12 (8.3%)	1
Triglycerides	5/12 (41.7%)	5
Vomitting	2/12 (16.7%)	2
WBC	4/12 (33.3%)	4
wt loss	2/12 (16.7%)	2
uric acid	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.