A DDI Study to Assess the Effect of INC280 on the PK of Midazolam and Caffeine in Patients With cMET-dysregulated Advanced Solid Tumors

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02520752
• Collaborator: (none)
• Enrollment: 37
• Locations: 12
• Arm: 1
• Actual Duration (Months): 21.1
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Drg-drug Interaction (DDI) study to assess the effect of INC280 on the pharmacokinetics of midazolam and caffeine in patients with cMET-dysregulated advanced solid tumors

Condition or Disease	Intervention/Treatment	Phase
cMET-dysregulated Advanced Solid Tumors	Drug: INC280; Drug: Midazolam; Drug: Caffeine	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I, Multicenter, Open-label, Single-sequence Drug-drug Interaction Study to Assess the Effect of INC280 on the Pharmacokinetics of Midazolam and Caffeine in Patients With cMET-dysregulated Advanced Solid Tumors
• Actual Study Start Date: Dec 10, 2015
• Actual Primary Completion Date: Jan 30, 2017
• Actual Study Completion Date: Sep 12, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INC280	Drug: INC280; Drug: Midazolam; Drug: Caffeine

Outcome Measures

Primary Outcome Measures

1. AUClast of midazolam and caffeine [Up to 72 hours post midazolam and caffeine dose]

   midazolam and caffeine pharmacokinetic parameters

2. AUCinf of midazolam and caffeine [Up to 72 hours post midazolam and caffeine dose]

   midazolam and caffeine pharmacokinetic parameter

3. Lambda_z of midazolam and caffeine [Up to 72 hours post midazolam and caffeine dose]

   midazolam and caffeine pharmacokinetic parameter

4. Cmax of midazolam and caffeine [Up to 72 hours post midazolam and caffeine dose]

   midazolam and caffeine pharmacokinetic parameter

5. Tmax of midazolam and caffeine [Up to 72 hours post midazolam and caffeine dose]

   midazolam and caffeine pharmacokinetic parameter

6. T1/2 of midazolam and caffeine [Up to 72 hours post midazolam and caffeine dose]

   midazolam and caffeine pharmacokinetic parameter

7. CL/F of midazolam and caffeine [Up to 72 hours post midazolam and caffeine dose]

   midazolam and caffeine pharmacokinetic parameter

8. Vz/F of midazolam and caffeine [Up to 72 hours post midazolam and caffeine dose]

   midazolam and caffeine pharmacokinetic parameter

Secondary Outcome Measures

1. Adverse events based on the CTCAE v4.03 grade (severity) and other safety data (e.g.,ECG, vital signs, laboratory results) [From consent to 30 days post last dose]

   To assess safety and tolerability of INC280 in patients with cMET-dysregulated advanced solid tumors

2. Overall response rate of patients treated with INC280 [Baseline, every 6 weeks]

   Overall response rate is defined as Complete Response and Partial Response calculated per RECIST 1.1, per investigator assessment

3. Disease control rate of patients treated with INC280 [Baseline, every 6 weeks]

   Disease control rate is defined as calculated as the proportion of patients with best overall response of Complete Response, Partial Response, or Stable Disease calculated per RECIST 1.1, per investigator assessment

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Patients must have:

• advanced solid tumors and have confirmed cMET dysregulation

• at least one measurable lesion as defined by RECIST 1.1.

• recovered from all toxicities related to prior anti-cancer therapies

• adequate organ function

• ECOG performance status (PS) of 0 or 1

Exclusion Criteria:

Patients must not have:

• known hypersensitivity to any of the excipients of INC280 or to benzodiazepines or known intolerance and hypersensitivity to caffeine

• symptomatic central nervous system (CNS) metastases who are neurologically unstable

• presence or history of carcinomatous meningitis

• history of another primary malignancy that is currently clinically significant or currently requires active intervention

• Clinically significant, uncontrolled heart diseases, including QTcF ≥ 450 ms (male patients), ≥ 460 ms (female patients) on the screening ECG

• Thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting INC280

• Major surgery within 4 weeks prior to starting INC280

• Patients receiving unstable or increasing doses of corticosteroids.

• Impairment of GI function or GI disease that may significantly alter the absorption of INC280

• Patients who have received or consumed, or are expected to receive or consume midazolam or caffeine-containing products (e.g., tea, coffee, cola), within 2 days prior to Day 1 and during the whole duration of the DDI phase (i.e., from Day -2 to Day 12)

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University School of Medicine/Winship Cancer Institute SC-2	Atlanta	Georgia	United States	30322
2	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
3	Novartis Investigative Site	Sofia		Bulgaria	1756
4	Novartis Investigative Site	Copenhagen		Denmark	DK-2100
5	Novartis Investigative Site	Dijon Cedex	Cote D Or	France	21034
6	Novartis Investigative Site	Pierre Benite		France	69310
7	Novartis Investigative Site	Rozzano	MI	Italy	20089
8	Novartis Investigative Site	Barcelona	Catalunya	Spain	08003
9	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
10	Novartis Investigative Site	Santiago de Compostela	Galicia	Spain	15706
11	Novartis Investigative Site	London		United Kingdom	W12 0HS
12	Novartis Investigative Site	Manchester		United Kingdom	M20 9BX

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Results for CINC280A2103 can be found on the Novartis Clinical trial results website

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02520752
• Other Study ID Numbers: CINC280A2103
• First Posted: Aug 13, 2015
• Last Update Posted: Dec 10, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: cMET, INC280, caffeine, midazolam
• Additional relevant MeSH terms: Neoplasms; Midazolam; Caffeine

Study Results

No Results Posted as of Dec 10, 2020