Phase II Trial of Vemurafenib and Sorafenib in Pancreatic Cancer

NCT05068752 | Completed Phase 2 Results FDA Drug

• 1 other identifier: HRI-Vemurafenib-Sorafenib-001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research is to determine the benefit of two oral chemotherapy drugs, Vemurafenib and Sorafenib, in individuals with KRAS mutated pancreatic cancer who have progressed on standard chemotherapy.

Conditions

Pancreas Cancer

Keywords

Pancreatic cancer; Pancreatic adenocarcinoma; Metastatic; KRAS; Phase 2

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate (DCR)

  Disease control rate (DCR) is defined as the combination of patients with complete response + partial response + stable disease at 16 weeks, divided by the total number of patients. Response is defined using RECIST v1.1 imaging criteria.

  Initiation of study treatment until 16 weeks.

Secondary Outcomes (5)

• Adverse Events Possibly or Definitely Related to Vemurafenib in Combination Wit Sorafenib

  Initiation of study treatment up to 30 days post treatment, an average of 90 days

• Progression-free Survival (PFS)

  Initiation of study treatment up to study completion, up to 2 years.

• Overall Survival (OS)

  Initiation of study treatment up to study completion, up to 2 years.

• Percent Change in Plasma Levels of Phospho-ERK From Baseline

  Initiation of study treatment to end of study treatment, up to 90 days.

• Percent Change in Plasma Levels of Phospho-AKT From Baseline

  Initiation of study treatment to end of study treatment, up to 90 days.

Study Arms (1)

Vemurafenib in Combination with Sorafenib

EXPERIMENTAL

Drug: Vemurafenib; Drug: Sorafenib

Interventions

Vemurafenib DRUG

Vemurafenib 480 mg PO BID daily given with Sorafenib 200 mg PO BID

Vemurafenib in Combination with Sorafenib

Sorafenib DRUG

Sorafenib 200 mg PO BID and Vemurafenib 480 mg PO BID daily

Vemurafenib in Combination with Sorafenib

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to understand and be willing to sign the written informed consent for the trial. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.
• Be ≥ 18 years of age on day of signing informed consent.
• Histologically confirmed cancer of the pancreas (KRAS mutated) with metastases and progression on at least ≥ 2 prior treatment regimens for their disease.
• Known mutation status of KRAS and BRAF kinases. For those patients in which this has not previously been determined, the patient must have an archival tumor specimen (primary or metastatic site) available to submit to confirm KRAS and BRAF status.
• Have a performance status of 0 or 1 on the ECOG performance scale.
• Demonstrate adequate organ function
• Female participants of childbearing potential must have a negative serum pregnancy test performed within 24 hours prior to receiving first dose of trial medication. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of trial treatment.
• Male participants must agree to use contraception during the treatment period and for at least 30 days after the last dose of trial treatment and refrain from donating sperm during this period.
• Patient must have QTC of ≤500ms.
• Subject must be able to swallow and retain oral medication
• Measurable disease per RECIST 1.1

You may not qualify if:

• Is currently participating and receiving trial therapy or has participated in a trial of an investigational agent and received trial therapy or used an investigational device within 2 weeks of the first dose of this trials' treatment.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Cycle 1/Day 1 or who has not recovered (i.e. NCI-CTC AE Version 5.0 ≤ Grade 1 at the time of signing informed consent) from adverse events due to a previously administered agent(s).
• Previous BRAF inhibitor use such as vemurafenib, GSK2118436 or sorafenib.
• If patient received major surgery, and has not yet recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Previously untreated or concurrent cancer that is distinct in primary site or histology from pancreatic cancer except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor. Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before study entry. All cancer treatments must be completed at least 3 years prior to study entry (i.e., signature date of the informed consent form).
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
• Uncontrolled hypertension (systolic pressure \>140 mm Hg or diastolic pressure \> 90 mm Hg \[NCI-CTCAE v5.0\] on repeated measurement) despite optimal medical management.
• Active of clinically significant cardiac disease
• Has history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has an active infection requiring systemic therapy.
• Evidence or history of bleeding diathesis or coagulopathy
• Patient with any pulmonary hemorrhage/bleeding event of NCI-CTCAE v5.0 ≥ Grade 2 within 4 weeks before initiating study treatment; any other hemorrhage/bleeding event of NCI-CTCAE v5.0 ≥ Grade 3 within 4 weeks before initiating study treatment.
• Patient with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) within 6 months of informed consent.
• Presence of a non-healing wound, non-healing ulcer, or bone fracture
• History of organ allograft (including corneal transplant).

Sponsors & Collaborators

• HonorHealth Research Institute: lead
• Bayer: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

Related Publications (1)

• Khawaja MR, Jameson G, Cridebring D, Shannon P, Han H, Moore J, Von Hoff D, Posner RG, Hlavacek WS, Kolch W, Kholodenko BN, Rukhlenko OS, Roe DJ, Wertheim BC, Borazanci E. Phase II Trial of Vemurafenib and Sorafenib Combination in Advanced KRAS-Mutated Metastatic Pancreatic Cancer. J Immunother Precis Oncol. 2026 Feb 10;9(1):17-24. doi: 10.36401/JIPO-25-20. eCollection 2026 Feb.

  PMID: 41766762 DERIVED

Related Links

• Phase II Trial of Vemurafenib and Sorafenib Combination in Advanced KRAS-Mutated Metastatic Pancreatic Cancer in: Journal of Immunotherapy and Precision Oncology Volume 9: Issue 1 \| Journal of Immunotherapy and Precision Oncology

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasm Metastasis

Interventions

Vemurafenib; Sorafenib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenylurea Compounds; Urea; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Limitations of this study include a single-arm, nonrandomized study design, a small sample size, and the lack of pharmacokinetic and pharmacodynamic (PK/PD) measurements.

Results Point of Contact

• Title: Erkut H. Borazanci, MD
• Organization: HonorHealth Research Institute

eborazanci@honorhealth.com

4805837120

Study Officials

• Erkut Borazanci, MD, MS

  HonorHealth Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2021
• First Posted: October 6, 2021
• Study Start: October 28, 2021
• Primary Completion: November 8, 2024
• Study Completion: December 13, 2024
• Last Updated: March 30, 2026
• Results First Posted: March 30, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)