Neoadjuvant Chemotherapy Followed by Radiation Therapy and Gemcitabine/Sorafenib/Vorinostat in Pancreatic Cancer

NCT02349867 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: MCC-12-07328NCI-2015-00017P30CA016059
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Determine the doses and schedule appropriate for phase 2 study of sorafenib and vorinostat with concurrent gemcitabine and radiation therapy (RT) as neoadjuvant treatment of pancreatic cancer following chemotherapy. Recommended phase II dose RP2Ds and schedule of sorafenib and vorinostat defined as the doses and schedule that are the same as or less than the maximum tolerated dose (MTD) and schedule.

Conditions

Pancreatic Adenocarcinoma; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Recurrent Pancreatic Carcinoma

Outcome Measures

Primary Outcomes (1)

• Recommended phase 2 dose and schedule

  Determine the doses and schedule appropriate for phase 2 study of sorafenib and vorinostat with concurrent gemcitabine and radiation therapy (RT) as neoadjuvant treatment of pancreatic cancer following chemotherapy.

  18-36 months

Secondary Outcomes (6)

• Number of participants with adverse events using National Cancer Institute CTCAE v4.0

  Up to 30 days following last administration of the chemoradiation treatment

• Tumor response (complete response or partial response) measured using RECIST version 1.1

  Up to 2 years

• Surgery

  Up to 2 years

• R0 Resection rate

  Up to 2 years

• Progression-free survival (PFS)

  Up to 2 Years

Study Arms (1)

Treatment (chemotherapy, chemoradiation)

EXPERIMENTAL

Participants receive gemcitabine IV infusion over 30 minutes (200 mg/m2 weekly) x 6, concurrent administration of oral sorafenib and oral vorinostat (both per dose-escalation schema), and concurrent RT( 3-Dimensional Conformal Radiation Therapy or Intensity-Modulated Radiation Therapy) administered at 1.8-Gy fractions to a total dose of 50.4 Gy over 5 ½ weeks (28 daily fractions).

Drug: Gemcitabine; Drug: Sorafenib; Drug: Vorinostat; Radiation: 3-Dimensional Conformal Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Other: RosetteSep; Other: DEPfff

Interventions

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd

Treatment (chemotherapy, chemoradiation)

Sorafenib DRUG

Given PO

Also known as: BAY 54-9085, Nexavar, SFN

Treatment (chemotherapy, chemoradiation)

Vorinostat DRUG

Given PO

Also known as: L-001079038, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid

Treatment (chemotherapy, chemoradiation)

3-Dimensional Conformal Radiation Therapy RADIATION

Undergo 3D CRT

Also known as: 3D-CRT, Conformal Therapy, Radiation Conformal Therapy

Treatment (chemotherapy, chemoradiation)

Intensity-Modulated Radiation Therapy RADIATION

Undergo IMRT

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Treatment (chemotherapy, chemoradiation)

RosetteSep OTHER

Circulating tumor cells (CTCs) will be captured and analyzed, when detected. Pancreatic cancer has been a difficult tumor in which to detect CTCs (41). Utilization of techniques that do not require cell surface marker expression will be explored. Samples will either be analyzed by negative-selection techniques (RosetteSep). Peripheral blood samples will be collected at several time-points for CTC enumeration and to evaluate CD95 density.

Also known as: negative-selection techniques

Treatment (chemotherapy, chemoradiation)

DEPfff OTHER

Circulating tumor cells (CTCs) will be captured and analyzed, when detected. Pancreatic cancer has been a difficult tumor in which to detect CTCs (41). Utilization of techniques that do not require cell surface marker expression will be explored. Samples will either be analyzed by with the ApoStream dielectrophoretic field-flow fractionation (DEPfff) enrichment device. Peripheral blood samples will be collected at several time-points for CTC enumeration and to evaluate CD95 density.

Also known as: ApoStream dielectrophoretic field-flow fractionation

Treatment (chemotherapy, chemoradiation)

Eligibility Criteria

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

You may qualify if:

• Adenocarcinoma of the pancreas
• Prior therapy with ≥ 1 prior systemic therapy over a period of at least 2 months (eg, at least two 4-week cycles of a regimen such as gemcitabine and nab-paclitaxel; or at least four 2-week cycles of a regimen such as FOLFOX, FOLFIRINOX, or FOLFIRI) -Candidate for additional therapy consisting of radiation with gemcitabine- radiosensitization.
• Able to initiate study treatment no later than 9 weeks from last dose of any antineoplastic component of prior therapy regimen.
• Recovery from ≥ grade 2 toxicities of prior therapy regimen to grade 1 or baseline, with the exception of anemia and lymphopenia and chronic residual toxicities that in the opinion of the investigator are not clinically relevant given the known safety/toxicity profiles of gemicitabine, sorafenib, and vorinostat (eg, alopecia, changes in pigmentation, stable endocrinopathies). Patients with ≤ grade 2 peripheral sensory or motor neuropathy are eligible..
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<= 3 x upper limit of normal (ULN) for the laboratory
• Total bilirubin \<= 1.5 x ULN for the laboratory at the time of enrollment, all forms of biliary stents allowed
• Creatinine clearance \>= 45 mL/min as calculated by the standard Cockcroft-Gault equation using age, actual weight, creatinine and gender
• International normalized ratio (INR) \<= 1.5
• Absolute neutrophil count (ANC) \>= 1,500/mm\^3
• Platelets \>= 100,000/mm\^3 (may not be transfused to meet this level for enrollment)
• Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) (version \[v\]1.1
• Ability to understand and the willingness to sign a written informed consent document
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
• Women of childbearing potential and men must agree to use a medically accepted form of birth control during the treatment and for 2 months following completion of study treatment

You may not qualify if:

• Prior radiotherapy for pancreatic cancer
• Prior surgical resection of pancreatic cancer
• Evidence of metastatic disease
• Any investigational agent within 4 weeks of study treatment initiation
• Diagnosis or treatment for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, any in situ malignancy, or low-risk prostate cancer after curative therapy
• Intolerance of protocol agents as follows:
• Known or presumed intolerance of gemcitabine, vorinostat or sorafenib
• Experienced any of the following toxicities with prior gemcitabine adminstration (if given): capillary leak syndrome, posterior reversible encephalopathy, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, unexplained dyspnea or other evidence of severe pulmonary toxicity, or severe hepatic toxicity
• Unable to swallow medication
• Suspected malabsorption or obstruction; note: use of pancreatic enzyme supplements is allowed to control malabsorption
• Contraindication to antiangiogenic agents, including:
• Bronchopulmonary hemorrhage/bleeding event \>= grade 2 (Common Terminology Criteria for Adverse Events \[CTCAE\] v4.0) within 12 weeks prior to of treatment
• Any other hemorrhage/bleeding event \>= grade 3 (CTCAE v4.0) within 12 weeks prior to initiation of treatment
• Serious non-healing wound, ulcer, or bone fracture
• Clinically significant cardiac disease, including major cardiac dysfunction, such as uncontrolled angina, clinical congestive heart failure with New York Heart Association (NYHA) class III or IV, ventricular arrhythmias requiring anti-arrhythmic therapy, recent (within 6 months) myocardial infarction or unstable coronary artery disease

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Related Publications (1)

• Booth L, Poklepovic A, Dent P. Neratinib decreases pro-survival responses of [sorafenib + vorinostat] in pancreatic cancer. Biochem Pharmacol. 2020 Aug;178:114067. doi: 10.1016/j.bcp.2020.114067. Epub 2020 Jun 3.

  PMID: 32504550 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Sorafenib; Vorinostat; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Anilides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Andrew Poklepovic, MD

  Massey Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2015
• First Posted: January 29, 2015
• Study Start: January 29, 2015
• Primary Completion: May 13, 2020
• Study Completion: May 13, 2022
• Last Updated: September 19, 2022

Record last verified: 2022-09

Locations

US (1)