Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Safety, Tolerability and PK Study of DCC-3116 in Patients With RAS or RAF Mutant Advanced or Metastatic Solid Tumors.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04892017
Recruitment Status : Recruiting
First Posted : May 19, 2021
Last Update Posted : August 2, 2021
Sponsor:
Information provided by (Responsible Party):
Deciphera Pharmaceuticals LLC

Brief Summary:
This is a Phase 1, multicenter, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, clinical activity, pharmacokinetics (PK), and pharmacodynamics (PD) of DCC-3116 as a single agent and in combination with trametinib in patients with advanced or metastatic solid tumors with RAS or RAF mutations. The study consists of 2 parts, a dose-escalation phase, and an expansion phase.

Condition or disease Intervention/treatment Phase
Pancreatic Ductal Adenocarcinoma Non-Small Cell Lung Cancer Colorectal Cancer Melanoma Advanced Solid Tumor Metastatic Solid Tumor Drug: DCC-3116 Drug: Trametinib Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, First-in-Human Study of DCC-3116 as a Single Agent and in Combination With Trametinib in Patients With Advanced or Metastatic Solid Tumors With RAS or RAF Mutations.
Actual Study Start Date : June 15, 2021
Estimated Primary Completion Date : April 2024
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
Drug Information available for: Trametinib

Arm Intervention/treatment
Experimental: Dose Escalation (Part 1-A Monotherapy)
DCC-3116 tablets in escalating dose cohorts given orally twice daily (BID) in 28-day cycles as monotherapy (single agent). If no DLT in 3 participants or 1 DLT/6 participants is observed, dose escalation will continue to the next planned dose cohort.
Drug: DCC-3116
Oral Tablet Formulation

Experimental: Dose Escalation (Part 1-B Combination)
Upon determination of the RP2D/MTD single agent, DCC-3116 will be dosed in combination with trametinib.
Drug: DCC-3116
Oral Tablet Formulation

Drug: Trametinib
Oral Tablet Formulation

Experimental: Expansion Cohort 1 (Part 2)
DCC-3116 tablets BID given in combination with trametinib in 28-day cycles to evaluate safety and preliminary efficacy of participants with pancreatic ductal adenocarcinoma (PDAC).
Drug: DCC-3116
Oral Tablet Formulation

Drug: Trametinib
Oral Tablet Formulation

Experimental: Expansion Cohort 2 (Part 2)
DCC-3116 tablets orally BID given in combination with trametinib in 28-day cycles to evaluate safety and preliminary efficacy of participants with non-small cell lung cancer (NSCLC).
Drug: DCC-3116
Oral Tablet Formulation

Drug: Trametinib
Oral Tablet Formulation

Experimental: Expansion Cohort 3 (Part 2)
DCC-3116 tablets orally BID given in combination with trametinib in 28-day cycles to evaluate safety and preliminary efficacy of participants with colorectal cancer (CRC).
Drug: DCC-3116
Oral Tablet Formulation

Drug: Trametinib
Oral Tablet Formulation

Experimental: Expansion Cohort 4 (Part 2)
DCC-3116 tablets orally BID given in combination with trametinib in 28-day cycles to evaluate safety and preliminary efficacy of participants with melanoma.
Drug: DCC-3116
Oral Tablet Formulation

Drug: Trametinib
Oral Tablet Formulation




Primary Outcome Measures :
  1. Incidence of Adverse Events [ Time Frame: Approximately 24 months ]
    Identify the observed adverse events, serious adverse events associated with DCC-3116

  2. Maximum tolerated dose (MTD) [ Time Frame: Approximately 18 months ]
    Identify the dose-limiting toxicities for each dose level tested and determine the maximum tolerated dose and recommended Phase 2 dose.

  3. Objective response rate (ORR) (Expansion Phase) [ Time Frame: Approximately 24 months ]
    Proportion of participants who achieve CR or PR per RECIST v1.1.


Secondary Outcome Measures :
  1. Duration of response (DoR) (Escalation Phase) [ Time Frame: Approximately 24 months ]
    DoR is defined as the time interval from the time that the measurement criteria are first met for CR or PR (whichever is first recorded) until the first date that the progressive disease is objectively documented.

  2. Clinical benefit rate (CBR) (Escalation Phase) [ Time Frame: Approximately 24 months ]
    The proportion of participants who achieve CR, PR, or SD per RECIST v1.1 at the corresponding assessment.

  3. Time to response (Escalation Phase) [ Time Frame: Approximately 24 months ]
    Time to response is defined as the time from initiation of treatment until the first assessment demonstrating CR or PR per RECIST v1.1.

  4. Progression-free survival (PFS) (Escalation Phase) [ Time Frame: Approximately 24 months ]
    PFS is defined as the time from initiation of treatment until documented disease progression per RECIST v1.1 or death.

  5. Maximum observed concentration (Cmax) [ Time Frame: Predose and up to 12 hours postdose. ]
    Measure the maximum observed concentration of DCC-3116 (single-agent and combination)

  6. Time to maximum observed concentration (Tmax) [ Time Frame: Predose and up to 12 hours postdose. ]
    Measure the time to maximum plasma concentration of DCC-3116 (single-agent and combination)

  7. Minimum observed concentration (Cmin) [ Time Frame: Predose and up to 12 hours postdose. ]
    Measure the minimum observed concentration of DCC-3116 (single-agent and combination)

  8. Area under the concentration-time curve( AUC) [ Time Frame: Predose and up to 12 hours postdose. ]
    Measure the AUC of DCC-3116 (single-agent and combination)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female participants ≥18 years of age at the time of informed consent.
  2. Dose Escalation Phase:

    1. Participants must have a histologically confirmed diagnosis of an advanced or metastatic solid tumor with a documented RAS or RAF mutation.
    2. Progressed despite standard therapies, and received at least 1 prior line of anticancer therapy.

      • Participants with a documented mutation in BRAF V600E or V600K must have received approved treatments known to provide clinical benefit prior to study entry.
  3. Dose Expansion Phase:

    1. Cohort 1: Pancreatic Ductal Adenocarcinoma.

      • Histologically confirmed PDAC with a documented mutation in KRAS or BRAF.
      • Received at least 1 prior line but no more than 3 prior lines of systemic therapy in the advanced or metastatic setting.
    2. Cohort 2: Non-Small Cell Lung Cancer

      • Histologically confirmed NSCLC with a documented mutation in KRAS, NRAS, or BRAF.
      • Received at least 2 prior lines but no more than 4 prior lines of systemic therapy in the advanced or metastatic setting.
    3. Cohort 3: Colorectal Cancer

      • Histologically confirmed CRC with a documented mutation in KRAS, NRAS, or BRAF.
      • Received at least 2 prior lines of systemic therapy in the advanced or metastatic setting.
    4. Cohort 4: Melanoma

      • Histologically confirmed melanoma with a documented mutation in NRAS or BRAF.
      • Received at least 2 prior lines but no more than 4 prior lines of systemic therapy in the advanced or metastatic setting.
  4. Must be able to provide tumor tissue sample
  5. Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 at Screening
  6. Adequate organ function and bone marrow function.
  7. If a female of childbearing potential must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements.
  8. Male participants must agree to follow contraception requirements.
  9. Must provide signed consent to participate in the study and is willing to comply with study-specific procedures.

Exclusion Criteria:

  1. Received prior anticancer therapy, including investigational therapy within 2 weeks or 5 × the half-life (whichever is shorter) prior to the first dose of study drug.
  2. Have not recovered from all toxicities from prior therapy according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
  3. Symptomatic central nervous system (CNS) metastases or presence of leptomeningeal disease Note: A participant with previously treated brain metastases may participate provided that they are stable.
  4. New York Heart Association Class III or IV heart disease, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension, congestive heart failure, or myocardial infarction within 6 months prior to the first dose of study drug.
  5. Prolongation of the QT interval corrected by Fridericia's formula (QTcF) based on repeated demonstration of QTcF >450 ms in males or >470 ms in females at screening, or history of long QT syndrome.
  6. Left ventricular ejection fraction (LVEF) <50% at Screening
  7. Systemic arterial thrombotic or embolic events
  8. Systemic venous thrombotic events
  9. A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy including uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes.
  10. Concurrent neuromuscular disorder that is associated with the potential of elevated creatine kinase.
  11. Bone disease that requires treatment.
  12. Major surgery within 4 weeks of the first dose of study drug. All surgical wounds must be healed and free of infection or dehiscence before the first dose of the study drug.
  13. Any other clinically significant comorbidities.
  14. For participants receiving DCC-3116 and trametinib combination: previous treatment with trametinib that resulted in treatment discontinuation due to intolerability as a result of an adverse event (AE) that was considered related to trametinib.
  15. Known allergy or hypersensitivity to any component of the investigational drug product.
  16. Known human immunodeficiency virus or hepatitis C infection only if the participant is taking medications that are excluded per protocol, active hepatitis B, or active hepatitis C infection.
  17. If female, the participant is pregnant or lactating.
  18. Ongoing or prior participation in an investigational drug study within 30 days of screening.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04892017


Contacts
Layout table for location contacts
Contact: Clinical Team 833-432-2237 clinicaltrials@deciphera.com

Locations
Layout table for location information
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Colin Weekes, MD, PhD    617-726-4000    cdweekes@mgh.harvard.edu   
United States, Texas
NEXT Oncology Recruiting
Austin, Texas, United States, 78758
Contact: Cynthia Deleon    210-307-0140    cdeleon@nextoncology.com   
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Ly Nguyen    713-563-2169    LMNguyen1@mdanderson.org   
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78229
Contact: Cynthia Deleon    210-307-0140    cdeleon@nextoncology.com   
Sponsors and Collaborators
Deciphera Pharmaceuticals LLC
Investigators
Layout table for investigator information
Study Director: Clinical Team Deciphera Pharmaceuticals LLC
Layout table for additonal information
Responsible Party: Deciphera Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT04892017    
Other Study ID Numbers: DCC-3116-01-001
First Posted: May 19, 2021    Key Record Dates
Last Update Posted: August 2, 2021
Last Verified: July 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Deciphera Pharmaceuticals LLC:
RAF
RAS
KRAS
NRAS
BRAF
DCC-3116
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Trametinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action