A Drug-drug Interaction (DDI) Study to Assess the Effect of INC280 on the Pharmacokinetics of Digoxin and Rosuvastatin in Patients With cMET-dysregulated Advanced Solid Tumors

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02626234
• Collaborator: (none)
• Enrollment: 32
• Locations: 15
• Arm: 1
• Actual Duration (Months): 16.7
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

the study aim to assess the effect of INC280 on the pharmacokinetics of digoxin and rosuvastatin in patients with cMET-dysregulated advanced solid tumors

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 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 Digoxin and Rosuvastatin in Patients With cMET-dysregulated Advanced Solid Tumors
• Actual Study Start Date: Dec 8, 2015
• Actual Primary Completion Date: Feb 28, 2017
• Actual Study Completion Date: Apr 28, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INC280	Drug: INC280; Drug: digoxin; Drug: rosuvastatin

Outcome Measures

Primary Outcome Measures

1. AUClast of digoxin and rosuvastatin [Up to 240 hours post digoxin and rosuvastatin dose]

   digoxin and rosuvastatin pharmacokinetics parameters

2. AUCinf of digoxin and rosuvastatin [Up to 240 hours post digoxin and rosuvastatin dose]

   digoxin and rosuvastatin pharmacokinetics parameters

3. Lambda_z of digoxin and rosuvastatin [Up to 240 hours post digoxin and rosuvastatin dose]

   digoxin and rosuvastatin pharmacokinetics parameters

4. Cmax of digoxin and rosuvastatin [Up to 240 hours post digoxin and rosuvastatin dose]

   digoxin and rosuvastatin pharmacokinetics parameters

5. Tmax of digoxin and rosuvastatin [Up to 240 hours post digoxin and rosuvastatin dose]

   digoxin and rosuvastatin pharmacokinetics parameters

6. T1/2 of digoxin and rosuvastatin [Up to 240 hours post digoxin and rosuvastatin dose]

   digoxin and rosuvastatin pharmacokinetics parameters

7. CL/F of digoxin and rosuvastatin [Up to 240 hours post digoxin and rosuvastatin dose]

   digoxin and rosuvastatin pharmacokinetics parameters

8. Vz/F of digoxin and rosuvastatin [Up to 240 hours post digoxin and rosuvastatin dose]

   digoxin and rosuvastatin pharmacokinetics parameters

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 [Up to 12 months]

   Overall response rate is defined as Complete Response and Partial Response calculated per RECIST 1.1, per investigator assessment from Day 1 until date of progression or death whichever comes first

3. Disease control rate of patients treated with INC280 [Up to 12 months]

   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 from Day 1 until date of progression or death whichever comes first

4. Concentration of INC280 during DDI phase [Day 22, Cycle 2 Day 1]

   INC280 concentrations collected on Day 22 during DDI phase and Cycle 2 Day 1 during post DDI phase along with a listing of individual values.

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

• prior treatment with cMET or HGF-targeting inhibitor

• known hypersensitivity to digoxin or rosuvastatin or its excipients

• 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 msec (male patients), ≥ 460 msec (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 are expected to receive digoxin or rosuvastatin within 21 days prior to the beginning of the DDI phase (Day 1) and for the duration of the DDI phase.

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 Phase 1 Working Group	Atlanta	Georgia	United States	30322
2	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
3	Novartis Investigative Site	Vienna		Austria	A-1090
4	Novartis Investigative Site	Edegem	Antwerpen	Belgium	2650
5	Novartis Investigative Site	Brno		Czechia	65653
6	Novartis Investigative Site	Ioannina	GR	Greece	455 00
7	Novartis Investigative Site	Athens		Greece	18547
8	Novartis Investigative Site	Milano	MI	Italy	20141
9	Novartis Investigative Site	Candiolo	TO	Italy	10060
10	Novartis Investigative Site	Bologna		Italy	40138
11	Novartis Investigative Site	Napoli		Italy	80131
12	Novartis Investigative Site	Madrid		Spain	28034
13	Novartis Investigative Site	Madrid		Spain	28222
14	Novartis Investigative Site	London		United Kingdom	W1G 6AD
15	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 CINC280A2105 can be found Novartis Clinical trials results website

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02626234
• Other Study ID Numbers: CINC280A2105
• First Posted: Dec 10, 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, rosuvastatin, digoxin
• Additional relevant MeSH terms: Neoplasms; Digoxin; Rosuvastatin Calcium

Study Results

No Results Posted as of Dec 10, 2020