NCT02703571

Brief Summary

Phase Ib dose escalation in advanced solid tumors to identify dose for Phase II dose expansion in advanced or metastatic pancreatic cancer and KRAS-mutant colorectal cancer. Open-label, nonrandomized.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
95

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jun 2016

Typical duration for phase_1

Geographic Reach
7 countries

15 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 4, 2016

Completed
5 days until next milestone

First Posted

Study publicly available on registry

March 9, 2016

Completed
4 months until next milestone

Study Start

First participant enrolled

June 29, 2016

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 24, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 24, 2019

Completed
Last Updated

December 21, 2020

Status Verified

September 1, 2020

Enrollment Period

3.2 years

First QC Date

March 4, 2016

Last Update Submit

December 17, 2020

Conditions

Solid Tumors for Phase IbPancreatic Cancer for Phase IIColorectal Cancer for Phase II

Keywords

TrametinibRibociclibLEE011TMT212advanced solid tumorspancreatic cancerKRAS-mutant colorectal cancercolorectal canceradvanced pancreatic cancermetastatic pancreatic cancer

Outcome Measures

Primary Outcomes (2)

  • Incidence of dose limiting toxicities (DLTs)

    Phase Ib part: The primary variable is the incidence of DLTs during the first 21 days of therapy. Estimation of the MTD of the combination treatment will be based upon the estimation of the probability of DLT during the first 21 days of therapy for patients in the DDS.

    21-day cycle one of treatment

  • Objective Response Rate (ORR)

    Phase II part: The primary variable used to evaluate the efficacy of the ribociclib and trametinib combination is the ORR, defined as the proportion of patients with a best overall confirmed CR or PR, as assessed per RECIST 1.1 by investigator assessment.

    Until progression of disease up to 1 year

Secondary Outcomes (6)

  • Duration of response (DOR)

    Until progression of disease up to 1 year

  • Time to response

    Until progression of disease up to 1 year

  • Disease control rate

    Until progression of disease up to 1 year

  • Progression disease rate

    Until progression of disease up to 1 year

  • Progression free survival

    Until progression of disease up to 1 year

  • +1 more secondary outcomes

Study Arms (1)

Advanced or metastatic solid tumors

EXPERIMENTAL

Patients in the Phase I portion of the study who have advanced or metastatic solid tumors

Drug: ribociclibDrug: Trametinib

Interventions

ribociclibDRUG

Combination treatment with LEE and TMT

Also known as: LEE011
Advanced or metastatic solid tumors
TrametinibDRUG

Combination treatment with LEE and TMT

Also known as: TMT212
Advanced or metastatic solid tumors

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Written informed consent must
  • Patient has histologically and/or cytologically confirmed malignancies:
  • Phase I:
  • Patients with advanced or metastatic solid tumors who have failed at least one prior line of systemic antineoplastic therapy in the advanced setting without a standard of care treatment option available;
  • Phase II:
  • Advanced or metastatic pancreatic adenocarcinoma who have failed at least one prior systemic antineoplastic therapies in the advanced setting
  • Advanced or metastatic KRAS-mutant CRC who have failed at least two prior systemic antineoplastic therapies in the advanced setting without a standard of care treatment option available. Testing for KRAS mutation in patients with CRC using locally approved diagnostic kit will be used for eligibility.
  • Phase II only: patient must have measurable disease
  • Patient has an ECOG performance status 0 or 1.
  • Patient has adequate bone marrow and organ function
  • Patient must have specified laboratory values within normal limits or corrected to within normal limits with supplements before the first dose of study medication on Cycle 1 Day 1:
  • Standard 12-lead ECG values defined

You may not qualify if:

  • Phase II only:
  • Patient has received prior treatment with a MEK inhibitor or a CDK4/6 inhibitor.
  • Phase I and Phase II:
  • Patient with a known hypersensitivity to the study drugs or any of the excipients of ribociclib or trametinib.
  • Patient is concurrently using other anti-cancer therapy.
  • Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to Cycle 1 Day 1
  • Patient has received local therapy to liver ≤ 3 months of C1D1
  • History of liver disease as follow:
  • Cirrhosis
  • Autoimmune hepatitis
  • Active viral hepatitis
  • Portal hypertension
  • Drug induced liver steatosis
  • Prior systemic anti-cancer treatment within 28 days prior to Cycle 1 Day 1
  • Prior therapy with anthracyclines at cumulative doses of 450 mg/ m2 or more for doxorubicin or 900 mg/m2 or more for epirubicin.
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

University of Miami Sylvester Comp Cancer Ctr

Miami, Florida, 33136, United States

Location

Dana Farber Cancer Center

Boston, Massachusetts, 02215, United States

Location

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Melbourne, Victoria, 3000, Australia

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

Novartis Investigative Site

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Novartis Investigative Site

Cologne, 50937, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Utrecht, 3584 CX, Netherlands

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Related Links

MeSH Terms

Conditions

Pancreatic NeoplasmsColorectal Neoplasms

Interventions

ribociclibtrametinib

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsEndocrine Gland NeoplasmsDigestive System DiseasesPancreatic DiseasesEndocrine System DiseasesIntestinal NeoplasmsGastrointestinal NeoplasmsGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: single group for phase 1b parallel group for phase 2
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 4, 2016

First Posted

March 9, 2016

Study Start

June 29, 2016

Primary Completion

September 24, 2019

Study Completion

September 24, 2019

Last Updated

December 21, 2020

Record last verified: 2020-09

Locations

CA(2)NL(2)ES(1)AU(1)US(6)BE(1)DE(2)