GSK1120212+GSK2141795 for Cervical Cancer

NCT01958112 | Terminated Phase 2 Results DMC

• 1 other identifier: 13-334
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is evaluating the combination of two drugs called GSK1120212 (trametinib) and GSK2141795 as a possible treatment for recurrent or persistent cervical cancer. Trametinib and GSK2141795 are drugs that may stop cancer cells from growing. Trametinib is a MEK inhibitor - it blocks a protein called MEK that is commonly overactive in tumor cells. GSK2141795 is an AKT inhibitor which blocks a pathway in cancer cells that is commonly overactive in tumor cells called the PI3kinase pathway. In this research study, the investigator is looking to see whether the combination of Trametinib and GSK2141795 is useful in treating recurrent and persistent cervical cancer. Additionally, the investigator is looking to see if participants whose tumors contain a particular genetic make-up will have better response to combination trametinib and GSK2141795. Participants' tumors will be tested for mutations in genes which could make some cancers more susceptible to trametinib and GSK2141795.

Conditions

Cervical Cancer

Keywords

Cervical Cancer; Cervical; Cervix

Outcome Measures

Primary Outcomes (1)

• Response Rate for the Combination of GSK1120212 (Trametinib) and GSK2141795 in Patients With Recurrent or Persistent Cervical Cancer.

  Response rate will be assessed by RECIST version 1.1.

  2 Years

Secondary Outcomes (4)

• Duration of Progression-free (PFS)

  2 Years

• Toxicity of GSK1120212 (Trametinib) and GSK2141795 as Measured by the Number of Participants With Adverse Events

  2 Years

• Mutation and Co-mutation Rates of Genes in the PI3K and RAS ERK Signaling Pathways in Recurrent Cervical Cancer Using High Throughput Targeted Mutational Analysis on Participant Tumor Samples.

  2 Years

• Overall Survival

  2 years

Study Arms (1)

GSK1120212 (trametinib) and GSK2141795

EXPERIMENTAL

GSK1120212 (trametinib) 1.5 mg QD + GSK2141795 50 mg QD in 28 day cycles

Drug: GSK1120212 (trametinib); Drug: GSK2141795

Interventions

GSK1120212 (trametinib) DRUG

Trametinib dose is 1.5 mg orally once per day

Also known as: Trametinib

GSK1120212 (trametinib) and GSK2141795

GSK2141795 DRUG

The dose of GSK2141795 is 50 mg orally once per day

GSK1120212 (trametinib) and GSK2141795

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recurrent or metastatic cervical cancer of any histology
• Measurable disease by RECIST 1.1.
• Prior Therapy:
• At least one prior chemotherapy regimen for management of cervical cancer. Radiation-sensitizing chemotherapy will not be counted as a systemic chemotherapy regimen
• Patients can have received one additional regimen for treatment
• No prior receipt of PI3K or RAS-ERK pathway inhibitors
• Age ≥ 18 years
• Life expectancy \> 3 mos
• ECOG performance status ≤ 2
• Participants must have normal organ function as defined below:
• Absolute Neutrophil Count (ANC)≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Hemoglobin \> 9.0/dL
• AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional ULN
• Total Bilirubin within normal institutional limits

You may not qualify if:

• No previous chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C,) or radiation therapy within 2 weeks prior to entering the study
• No use of investigational agents nor have participated in an investigational trial within the past 4 weeks (or five half-lives whichever is shorter; with a minimum of 14 days from the last dose).
• Presence of active GI disease that could affect GI absorption or predispose a subject to GI ulceration.
• Evidence of mucosal of internal bleeding
• Major surgery within the last 4 weeks
• No Type 1 diabetes; however, patients with Type 2 diabetes are eligible if diagnosed ≥ 6 months prior to enrollment and if hemoglobin A1C (HbA1C) ≤ 8% at screening.
• Symptomatic or unstable brain metastases or asymptomatic and untreated but \> 1 cm in the longest dimension
• Symptomatic or untreated leptomeningeal or spinal cord compression.
• Individuals with a history of a different malignancy are ineligible except for the following circumstances: the following cancers are eligible if diagnosed and treated within the past 3 years: breast cancer in situ and basal cell or squamous cell carcinoma of the skin, stage I colon carcinoma confined to a polyp.
• Any serious and/or unstable pre-existing medical disorders
• Known infection with HIV, Hepatitis B Virus, or Hepatitis C Virus
• Chronic use of drugs that are strong inhibitors or inducers of p450 CYP3A4
• known immediate or delayed hypersensitivity reaction or idiosyncrasy to study drugs
• History of interstitial lung disease or pneumonitis.
• Presence of cardiac metastases

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Novartis: collaborator
• National Comprehensive Cancer Network: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

trametinib; GSK2141795

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Results Point of Contact

• Title: Dr. Ursula Matulonis
• Organization: Dana-Farber Cancer Institute

ursula_matulonis@dfci.harvard.edu

617-632-2334

Study Officials

• Ursula A. Matulonis, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 4, 2013
• First Posted: October 8, 2013
• Study Start: October 1, 2013
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: May 31, 2019
• Results First Posted: January 2, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)