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Preoperative Valproic Acid and Radiation Therapy for Rectal Cancer (V-shoRT-R3)

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: NCT01898104
Recruitment Status : Recruiting
First Posted : July 12, 2013
Last Update Posted : March 24, 2023
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute, Naples

Study Description
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Brief Summary:
The purpose of this study is to first determine the maximum tolerated dose of capecitabine given alone or in combination with valproic acid during preoperative short-course radiotherapy (Phase 1). The next part of the study (Phase 2)will explore whether the addition of valproic acid or the addition of capecitabine to short-course radiotherapy, before optimal radical surgery might increase the pathologic complete tumor regression rate in patients with low-moderate risk rectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Radiation: preoperative radiation therapy Drug: Valproic Acid Drug: Capecitabine Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 152 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2 Study of Valproic Acid and Short-course Radiotherapy Plus Capecitabine as preoperatIve Treatment in Low-moderate Risk Rectal Cancer
Study Start Date : May 2012
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : April 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: SCRT
short course radiotherapy (SCRT) alone 25 Gy in 5 fractions over one week.
 Radiation: preoperative radiation therapy
25 Gy in 5 fractions over 1 week
Active Comparator: V-SCRT
Valproic acid (V) + short course radiotherapy
 Radiation: preoperative radiation therapy
25 Gy in 5 fractions over 1 week

Drug: Valproic Acid
Active Comparator: C-SCRT
capecitabine (C) + short course radiotherapy
 Radiation: preoperative radiation therapy
25 Gy in 5 fractions over 1 week

Drug: Capecitabine
Active Comparator: VC-SCRT
valproic acid + capecitabine + short course radiotherapy
 Radiation: preoperative radiation therapy
25 Gy in 5 fractions over 1 week

Drug: Valproic Acid
Drug: Capecitabine


Outcome Measures
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Primary Outcome Measures :
  1. maximum tolerated dose of capecitabine, given alone or in combination with valproic acid [ Time Frame: up to 3 weeks ]
    Phase 1 primary objective

  2. number of patients with complete pathological tumor regression [ Time Frame: 8 weeks ]
    evaluated at definitive surgery, planned 8 weeks after the end of radiotherapy, in all the study arms of Phase 2


Secondary Outcome Measures :
  1. overall survival [ Time Frame: 1 year ]
  2. number of patients alive with disease progression [ Time Frame: one year ]
  3. number of patients with pathologic complete response [ Time Frame: 2 months ]
  4. changes in quality of life from baseline [ Time Frame: up to 3 months ]

Other Outcome Measures:
  1. evaluation of predictive factors [ Time Frame: 2 months ]
    description of predictive role of early tumor metabolic changes measured by PET scan

  2. predictive and prognostic factors of tumor and circulating cells [ Time Frame: 2 months ]
    descriptive exploratory analyses


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

• Patients with histologically confirmed diagnosis of adenocarcinoma of rectum falling into one of the following categories: T2N0 located at <2 cm from anal verge T2N1 or T3N0-N1, located at >5 cm and <12 cm from anal verge and infiltration of perirectal fat up to a distance of 1 mm from mesorectal fascia (MRF) evaluated by MRI.

  • Age ≥18 and ≤ 70
  • ECOG Performance Status ≤1
  • Effective contraception for both male and female patients if the risk of conception exist
  • Signed written informed consent

Exclusion Criteria:

  • Any previous treatment for rectal cancer
  • Previous pelvic radiotherapy
  • Presence of metastatic disease
  • Recurrent rectal tumor
  • Patient with Familial Adenomatosis Polyposis (FAP) or Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
  • History of inflammatory bowel disease or active disease
  • Any concurrent malignancy except for adequately treated basocellular carcinoma of the skin or in situ carcinoma of cervix uteri. Patients with a previous malignancy but without evidence of disease for 5 years will be allowed to enter the trial.
  • Neutrophils < 2000/mm3 or platelets < 100.000/ mm3 or haemoglobin <9 gr/dl.
  • Creatinine levels indicating renal clearance of <50 ml/min
  • GOT and/or GPT > 2.5 time the UNL and/or bilirubin >1.5 time the upper-normal limits (UNL)
  • Significant cardiovascular comorbidity (e.g. myocardial infarction, superior vena cava [SVC] syndrome, patients with an ejection fraction of <50%) or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia.
  • History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia.
  • Patients with long QT-syndrome or QTc interval duration > 480 msec or concomitant medication with drugs prolonging QTc (see list in the appendix)
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency
  • HIV positive patients
  • Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease.
  • Known or suspected hypersensitivity to any of the study drugs.
  • Patient who have had prior treatment with an HDAC inhibitor and patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid.
  • Concurrent uncontrolled medical conditions that might contraindicate study drugs.
  • Major surgical procedure, within 28 days prior to study treatment start.
  • Pregnant or lactating women.
  • Women of childbearing potential with either a positive or no pregnancy test at baseline (NB. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.
  • Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.
Contacts and Locations
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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): NCT01898104


Contacts
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Contact: Antonio Avallone, M.D. +39 081 5903629 avalloneantonio@libero.it
Contact: Maria Carmela Piccirillo, M.D. +39 081 5903571 marilina.piccirllo@usc-intnapoli.net

Locations
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Italy
Istituto Nazionale Tumori Fondazione G. Pascale Recruiting
Napoli, Italy
Sponsors and Collaborators
National Cancer Institute, Naples
Investigators
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Principal Investigator: Antonio Avallone, M.D. National Cancer Institute, Naples
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: National Cancer Institute, Naples
ClinicalTrials.gov Identifier: NCT01898104    
Other Study ID Numbers: V-shoRT-R3
2012-002831-28 ( EudraCT Number )
First Posted: July 12, 2013    Key Record Dates
Last Update Posted: March 24, 2023
Last Verified: March 2023
Keywords provided by National Cancer Institute, Naples:
rectal
low risk
moderate risk
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Valproic Acid
 Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Anticonvulsants
Enzyme Inhibitors
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs