Ponatinib for Squamous Cell Lung and Head and Neck Cancers

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01761747
• Collaborator: (none)
• Enrollment: 3
• Locations: 4
• Arm: 1
• Duration (Months): 17
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is being studied. It also means that the FDA has not yet approved ponatinib for use in patients, including people with your type of cancer.

In order to participate on this study, it must first be determined whether or not a patient's lung or head and neck squamous cell cancer (SCC) has an alteration in FGFR kinase is made from an experimental test on your squamous cell cancer tissue sample. This experimental test is a "genetic test" or "genotyping test", which is a method used to study a tumor's genes. The results are for research purposes only and are not considered "genetic testing" for the purpose of diagnosing medical conditions. Cancers develop as a result of changes that occur in human genetic material (DNA); these changes are called mutations or alterations. This experimental test gives no information about any of the genes in the normal cells of the patient's body, but it helps identify abnormal genes (like FGFR kinase mutations or alterations) usually found only in cancer cells. We will use this experimental test to determine whether or not a tumor contains a required alteration/mutation and thus may respond to ponatinib.

Ponatinib is an investigational, oral anti-cancer drug designed to inhibit abnormal proteins found in cancer cells and may cause those cancer cells to die. In laboratory testing, ponatinib has been shown to inhibit a family of proteins called FGFR kinases, and this genetic alteration/mutation has been found in some squamous cell lung cancers. There is laboratory evidence that alterations/mutations in FGFR kinases in squamous cell lung cancers may be driving the growth of these tumors and that inhibiting these FGFR kinases with ponatinib may decrease or stop the growth of lung SCC.

In this research study, we are looking to see if the study drug, ponatinib, can keep cancer from growing.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer, Head and Neck Cancer	Drug: ponatinib	Phase 2/Phase 3

Detailed Description

Patients will be asked to undergo some screening tests or procedures to find out if they can be in the research study. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that an individual does not take part in the research study. If a patient has had some of these tests or procedures recently, they may or may not have to be repeated. These screening tests include: medical history, physical examination, vital signs, performance status, assessment of tumor(s), CT scan or MRI scan of brain, routine blood tests, urine pregnancy test for women of childbearing potential and electrocardiogram. Additionally at the time of screening patients will undergo collection of an archival tumor tissue sample for tumor mutation testing.

If a patient takes part in this research study, he or she will be given a study drug-dosing calendar for each treatment cycle. Each treatment cycle lasts 4 weeks during which time the patient will be taking the study drug by mouth daily. The number of cycles the patient will receive will depend on how the patient is tolerating the ponatinib and if your cancer has worsened.

There is a possibility that the following tests or procedures may need to be done at times other than those listed below. These may be done if the research doctors determine they are medically necessary to monitor illness or any side effects a patient may be experiencing. It is important that patients call their research doctor if at any time they are experiencing side effects they cannot tolerate.

During all cycles patients will have a physical exam and be asked questions about their general health and specific questions about any problems that they might be having and any medications they might be taking.

If the patient's disease progresses while you are on this study, they will be given the option of consenting to a new biopsy for research purposes at no financial cost to the patient.

The investigators would like to keep track of your medical condition for the rest of each patient's life. The investigators would like to do this by calling every six months to see how the patients are doing. Keeping in touch with checking their condition helps the investigators look at the long-term effects of the research study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Ponatinib in Advanced Lung and Head and Neck Cancers With FGFR Kinase Alterations
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ponatinib Treatment Arm Ponatinib taken by mouth daily	Drug: ponatinib; Other Names: AP24534

Outcome Measures

Primary Outcome Measures

1. Response Rate of Patients With Lung or Head and Neck SCC Treated With Ponatinib [2 years]

   Investigate the response rate of patients with previously treated lung or head and neck SCC to ponatinib as defined by the proportion of subjects with investigator-assessed confirmed complete response (CR) or partial response (PR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR."

Secondary Outcome Measures

1. Prevalence of Specific FGFR Amplifications/Mutations in the Study Population [2 years]

   Test tumor DNA using molecular assays to measure the frequency of FGFR amplifications and mutations in study patients

2. Progression-free Survival [2 years]

   Establish the progression-free survival of patients with SCC treated with ponatinib as defined by time to development of progression by RECIST criteria.

3. Define Toxicities of Ponatinib [2 years]

   Number of Participants with Adverse Events as a Measure of Safety and Tolerability

4. Overall Survival [2 years]

   Measure the overall survival time of patients treated with ponatinib

5. Disease Control [2 years]

   Measure the disease control rate of patients treated with ponatinib

6. Determine the Correlation FGFR Amplifications/Mutations With Patient Age, Sex, Disease Stage, Prior Response to Treatment and Smoking History [2 years]

   For subjects with FGFR amplifications and for FGFR mutations we will ascertain the age, sex, disease stage, prior response to treatment and smoking history from past medical records and measure whether there are differences in these variables among subjects with amplification versus mutation.

7. Define the Response Rate to Ponatinib is Patients With FGFR Amplifications Versus Mutations [2 years]

   Identify the response rate to ponatinib for FGFR specific FGFR amplifications/mutations.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Measurable disease

• Documented evidence of disease progression following most recent therapy

• Estimated life expectancy greater than 12 weeks

Exclusion Criteria:

• Pregnant or breastfeeding

• Prior chemotherapy or brain radiotherapy within 4 weeks of entering study

• Receiving other investigational agents

• Untreated or progressive brain metastases

• Prior treatment with or allergic reactions attributed to compounds of similar chemical or biologic composition to ponatinib

• Known HIV positive on combination antiretroviral therapy

• Clinically uncontrolled hypertension

• Previous or concurrent malignancy except adequately treated basal or squamous cell skin cancer, in situ carcinoma of the cervix, or other solid tumor treated curatively and without evidence of recurrence for at least 5 years

• Active or uncontrolled clinically significant infection

• Chronic GI disease that may affect bioavailability of ponatinib

• History of significant bleeding disorder unrelated to cancer

• Uncontrolled intercurrent illness

• Clinically significant ventricular arrythmia

• History of chronic pancreatitis, alcohol abuse or uncontrolled hypertriglyceridemia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02214
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
3	Brigham and Women's Hospital	Boston	Massachusetts	United States	02215
4	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Dana-Farber Cancer Institute

Investigators

• Principal Investigator: Peter Hammerman, MD, PhD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Peter S. Hammerman, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT01761747
• Other Study ID Numbers: 12-327
• First Posted: Jan 7, 2013
• Last Update Posted: Dec 23, 2014
• Last Verified: Dec 1, 2014

• Keywords provided by Peter S. Hammerman, Principal Investigator, Dana-Farber Cancer Institute: Squamous Cell Carcinoma
• Additional relevant MeSH terms: Head and Neck Neoplasms; Ponatinib

Study Results

Participant Flow

Arm/Group Title	Ponatinib Treatment Arm
Arm/Group Description	Ponatinib taken by mouth daily ponatinib
Period Title: Overall Study
STARTED	3
COMPLETED	2
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Ponatinib Treatment Arm
Arm/Group Description	Ponatinib taken by mouth daily ponatinib
Overall Participants	3
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	3 100%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	3 100%
Region of Enrollment (participants) [Number]
United States	3 100%
Disease (participants) [Number]
Number [participants]	3 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate of Patients With Lung or Head and Neck SCC Treated With Ponatinib
Description	Investigate the response rate of patients with previously treated lung or head and neck SCC to ponatinib as defined by the proportion of subjects with investigator-assessed confirmed complete response (CR) or partial response (PR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR."
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ponatinib Treatment Arm
Arm/Group Description	Ponatinib taken by mouth daily ponatinib
Measure Participants	3
Number [percentage of subjects with response]	0

2. Secondary Outcome

Title	Prevalence of Specific FGFR Amplifications/Mutations in the Study Population
Description	Test tumor DNA using molecular assays to measure the frequency of FGFR amplifications and mutations in study patients
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

2 participants had FGFR amplification, one with FGFR mutation

Arm/Group Title	Ponatinib Treatment Arm
Arm/Group Description	Ponatinib taken by mouth daily ponatinib
Measure Participants	3
Number [participants]	3 100%

3. Secondary Outcome

Title	Progression-free Survival
Description	Establish the progression-free survival of patients with SCC treated with ponatinib as defined by time to development of progression by RECIST criteria.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ponatinib Treatment Arm
Arm/Group Description	Ponatinib taken by mouth daily ponatinib
Measure Participants	2
Mean (Full Range) [days]	44

4. Secondary Outcome

Title	Define Toxicities of Ponatinib
Description	Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ponatinib Treatment Arm
Arm/Group Description	Ponatinib taken by mouth daily ponatinib
Measure Participants	3
Number [participants]	2 66.7%

5. Secondary Outcome

Title	Overall Survival
Description	Measure the overall survival time of patients treated with ponatinib
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ponatinib Treatment Arm
Arm/Group Description	Ponatinib taken by mouth daily ponatinib
Measure Participants	3
Mean (Full Range) [days]	276

6. Secondary Outcome

Title	Disease Control
Description	Measure the disease control rate of patients treated with ponatinib
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ponatinib Treatment Arm
Arm/Group Description	Ponatinib taken by mouth daily ponatinib
Measure Participants	2
Number [percentage of subjects]	0

7. Secondary Outcome

Title	Determine the Correlation FGFR Amplifications/Mutations With Patient Age, Sex, Disease Stage, Prior Response to Treatment and Smoking History
Description	For subjects with FGFR amplifications and for FGFR mutations we will ascertain the age, sex, disease stage, prior response to treatment and smoking history from past medical records and measure whether there are differences in these variables among subjects with amplification versus mutation.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Too few subjects were enrolled on study to permit this outcome measure analysis.

Arm/Group Title	Ponatinib Treatment Arm
Arm/Group Description	Ponatinib taken by mouth daily ponatinib
Measure Participants	0

8. Secondary Outcome

Title	Define the Response Rate to Ponatinib is Patients With FGFR Amplifications Versus Mutations
Description	Identify the response rate to ponatinib for FGFR specific FGFR amplifications/mutations.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

There were no observed responses on study so this outcome could not be determined.

Arm/Group Title	Ponatinib Treatment Arm
Arm/Group Description	Ponatinib taken by mouth daily ponatinib
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	One individual withdrew consent the day after enrolling on study and was not dosed. Therefore only two individuals were evaluable for treatment-related toxicities.
Arm/Group Title	Ponatinib Treatment Arm
Arm/Group Description	Ponatinib taken by mouth daily ponatinib
All Cause Mortality
	Ponatinib Treatment Arm
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ponatinib Treatment Arm
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Gastrointestinal disorders
Pancreatits	1/2 (50%)
Other (Not Including Serious) Adverse Events
	Ponatinib Treatment Arm
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Gastrointestinal disorders
Diarrhea	1/2 (50%)
Mucositis	1/2 (50%)
Hepatitis	2/2 (100%)
General disorders
Fatigue	2/2 (100%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/2 (50%)
Myalgia	1/2 (50%)
Nervous system disorders
Neuropathy	1/2 (50%)
Skin and subcutaneous tissue disorders
Rash	1/2 (50%)

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.