Tivantinib in Treating Patients With Previously Treated Malignant Mesothelioma

• ClinicalTrials.gov Identifier: NCT01861301
• Recruitment Status: Terminated
• First Posted: May 23, 2013
• Results First Posted: October 24, 2016
• Last Update Posted: October 24, 2016
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Epithelioid Mesothelioma; Recurrent Malignant Mesothelioma; Sarcomatoid Mesothelioma; Stage II Pleural Mesothelioma; Stage III Pleural Mesothelioma; Stage IV Pleural Mesothelioma
• Interventions: Other: Laboratory Biomarker Analysis; Drug: Tivantinib
• Enrollment: 18

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Treatment (Tivantinib)
Arm/Group Description	Patients receive tivantinib 360 mg PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
Started	18
Completed	18
Not Completed	0

Baseline Characteristics

Arm/Group Title		Treatment (Tivantinib)
Arm/Group Description		Patients receive tivantinib 360 mg PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.
Overall Number of Baseline Participants		18
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	18 participants
		66.5; (19 to 81)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	18 participants
	Female	7 38.9%
	Male	11 61.1%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	18 participants
		18

Outcome Measures

1. Primary Outcome

Title	Objective Radiologic Response Rate (Complete or Partial Response) Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or 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	Up to 1 year

Outcome Measure Data

Analysis Population Description

Note: Study terminated for futility due to insufficient number of objective responders in first stage.

Arm/Group Title	Treatment (Tivantinib)
Arm/Group Description:	Patients receive tivantinib 360 mg PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	18
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	0; (0 to 18.5)

2. Secondary Outcome

Title	Incidence of Adverse Events, Graded Per NCI CTCAE Version 4
Description	Grade 3 or higher AE of any type, regardless of attribution.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Tivantinib)
Arm/Group Description:	Patients receive tivantinib 360 PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	18
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	22.2; (6.4 to 47.6)

3. Secondary Outcome

Title	Overall Survival
Description	Analyzed using the Kaplan-Meier method.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Tivantinib)
Arm/Group Description:	Patients receive tivantinib 360 PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	18
Median (95% Confidence Interval); Unit of Measure: Months
	12.2; (7.1 to 22.2)

4. Secondary Outcome

Title	Progression-free Survival
Description	Time to disease progression or death from any cause. Analyzed using the Kaplan-Meier method.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Tivantinib)
Arm/Group Description:	Patients receive tivantinib 360 mg PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	18
Median (95% Confidence Interval); Unit of Measure: Months
	1.9; (1.8 to 5.4)

5. Other Pre-specified Outcome

Title	Change in Baseline Levels of Continuous or Ordinal Markers (e.g., Serum HGF/MET IHC) Between Responders and Non-responders
Description	Fisher's exact test will be performed for binary variables (e.g., presence/absence of MET gene amplification). Paired t-tests or Wilcoxon signed-ranks test, whichever is appropriate, will be used to examine the changes with treatment in the laboratory correlates that are continuous and McNemar's test will be used for binary markers.
Time Frame	Baseline to 1 year

Outcome Measure Data Not Reported

6. Other Pre-specified Outcome

Title	Change in Serum HGF or MET IHC and Tumor Size Change (Percent Reduction in Sum of Longest Diameters)
Description	Will be evaluated by Spearman's rank correlation coefficient.
Time Frame	Baseline to 1 year

Outcome Measure Data Not Reported

7. Other Pre-specified Outcome

Title	Association Between Baseline HGF, MET Gene Amplification, MET IHC and PFS
Description	Will be evaluated using the Cox regression model.
Time Frame	Baseline to 1 year

Outcome Measure Data Not Reported

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Treatment (Tivantinib)
Arm/Group Description	Patients receive tivantinib 360 PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
	Treatment (Tivantinib)
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Treatment (Tivantinib)
	Affected / at Risk (%)
Total	3/18 (16.67%)
Gastrointestinal disorders
Small intestinal obstruction	1/18 (5.56%)
Respiratory, thoracic and mediastinal disorders
Hypoxia *	1/18 (5.56%)
Lung infection *	1/18 (5.56%)
Pleuritic pain *	1/18 (5.56%)
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Treatment (Tivantinib)
	Affected / at Risk (%)
Total	17/18 (94.44%)
Blood and lymphatic system disorders
Anemia *	9/18 (50.00%)
Cardiac disorders
Palpitations *	1/18 (5.56%)
Sinus bradycardia *	3/18 (16.67%)
Ear and labyrinth disorders
Ear pain *	1/18 (5.56%)
Eye disorders
Blurred vision *	1/18 (5.56%)
Gastrointestinal disorders
Abdominal distension *	1/18 (5.56%)
Abdominal pain *	2/18 (11.11%)
Constipation *	2/18 (11.11%)
Diarrhea *	4/18 (22.22%)
Gastroesophageal reflux disease *	1/18 (5.56%)
Nausea/vomiting *	3/18 (16.67%)
General disorders
Fatigue *	14/18 (77.78%)
Fever *	3/18 (16.67%)
Flu like symptoms *	1/18 (5.56%)
Jitteriness *	1/18 (5.56%)
Non-cardiac chest pain *	1/18 (5.56%)
Pain *	4/18 (22.22%)
Infections and infestations
Urinary tract infection *	1/18 (5.56%)
Injury, poisoning and procedural complications
Bruising *	1/18 (5.56%)
Investigations
Alanine aminotransferase increased *	3/18 (16.67%)
Alkaline phosphaase increased *	2/18 (11.11%)
Aspartate aminotransferase increase *	5/18 (27.78%)
Creatinine increased *	4/18 (22.22%)
Lymphocyte count decreased *	1/18 (5.56%)
Platelet count decreased *	1/18 (5.56%)
White blood cell decreased *	4/18 (22.22%)
Metabolism and nutrition disorders
Anorexia *	3/18 (16.67%)
Dehydration *	1/18 (5.56%)
Hypercalcemia *	1/18 (5.56%)
Hyperglycemia *	1/18 (5.56%)
Hyperkalemia *	4/18 (22.22%)
Hypoalbuminemia *	5/18 (27.78%)
Hypocalcemia *	1/18 (5.56%)
Hypokalemia *	1/18 (5.56%)
Hyponatremia *	3/18 (16.67%)
Hypophosphatemia *	3/18 (16.67%)
Musculoskeletal and connective tissue disorders
Back pain *	1/18 (5.56%)
Chest wall pain *	2/18 (11.11%)
Nervous system disorders
Dizziness *	1/18 (5.56%)
Headache *	2/18 (11.11%)
Memory impairment *	1/18 (5.56%)
Neuropathy-sensory *	2/18 (11.11%)
Presyncope *	1/18 (5.56%)
Psychiatric disorders
Anxiety *	2/18 (11.11%)
Renal and urinary disorders
Chronic kidney disease *	1/18 (5.56%)
Reproductive system and breast disorders
Testicular pain *	1/18 (5.56%)
Respiratory, thoracic and mediastinal disorders
Cough *	3/18 (16.67%)
Dyspnea *	7/18 (38.89%)
Edema *	1/18 (5.56%)
Nasal congestion *	1/18 (5.56%)
Productive cough *	1/18 (5.56%)
Respiratory failure *	1/18 (5.56%)
Sore throat *	2/18 (11.11%)
Skin and subcutaneous tissue disorders
Rash maculo-papular *	1/18 (5.56%)
Vascular disorders
Hypertension *	1/18 (5.56%)
Hypotension *	1/18 (5.56%)
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS 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.

Results Point of Contact

• Name/Title: Hedy Kindler, MD
• Organization: University of Chicago
• Phone: 773-702-0360
• EMail: hkindler@medicine.bsd.uchicago.edu

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01861301
• Other Study ID Numbers: NCI-2013-00937; NCI-2013-00937 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 12-2158; 12-2158 ( Other Identifier: University of Chicago Comprehensive Cancer Center ); 9267 ( Other Identifier: CTEP ); N01CM00071 ( U.S. NIH Grant/Contract ); P30CA014599 ( U.S. NIH Grant/Contract )
• First Submitted: May 20, 2013
• First Posted: May 23, 2013
• Results First Submitted: August 26, 2016
• Results First Posted: October 24, 2016
• Last Update Posted: October 24, 2016