NCT01898104

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
152

participants targeted

Target at P75+ for phase_1 colorectal-cancer

Timeline
Completed

Started May 2012

Longer than P75 for phase_1 colorectal-cancer

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2012

Completed
1.2 years until next milestone

First Submitted

Initial submission to the registry

July 2, 2013

Completed
10 days until next milestone

First Posted

Study publicly available on registry

July 12, 2013

Completed
10.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2023

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2024

Completed
Last Updated

March 24, 2023

Status Verified

March 1, 2023

Enrollment Period

11.5 years

First QC Date

July 2, 2013

Last Update Submit

March 23, 2023

Conditions

Colorectal Cancer

Keywords

rectallow riskmoderate risk

Outcome Measures

Primary Outcomes (2)

  • maximum tolerated dose of capecitabine, given alone or in combination with valproic acid

    Phase 1 primary objective

    up to 3 weeks

  • number of patients with complete pathological tumor regression

    evaluated at definitive surgery, planned 8 weeks after the end of radiotherapy, in all the study arms of Phase 2

    8 weeks

Secondary Outcomes (4)

  • overall survival

    1 year

  • number of patients alive with disease progression

    one year

  • number of patients with pathologic complete response

    2 months

  • changes in quality of life from baseline

    up to 3 months

Other Outcomes (2)

  • evaluation of predictive factors

    2 months

  • predictive and prognostic factors of tumor and circulating cells

    2 months

Study Arms (4)

SCRT

ACTIVE COMPARATOR

short course radiotherapy (SCRT) alone 25 Gy in 5 fractions over one week.

Radiation: preoperative radiation therapy

V-SCRT

ACTIVE COMPARATOR

Valproic acid (V) + short course radiotherapy

Radiation: preoperative radiation therapyDrug: Valproic Acid

C-SCRT

ACTIVE COMPARATOR

capecitabine (C) + short course radiotherapy

Radiation: preoperative radiation therapyDrug: Capecitabine

VC-SCRT

ACTIVE COMPARATOR

valproic acid + capecitabine + short course radiotherapy

Radiation: preoperative radiation therapyDrug: Valproic AcidDrug: Capecitabine

Interventions

preoperative radiation therapyRADIATION

25 Gy in 5 fractions over 1 week

C-SCRTSCRTV-SCRTVC-SCRT
Valproic AcidDRUG
V-SCRTVC-SCRT
CapecitabineDRUG
C-SCRTVC-SCRT

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, Italy

RECRUITING

Related Publications (1)

  • Avallone A, Piccirillo MC, Delrio P, Pecori B, Di Gennaro E, Aloj L, Tatangelo F, D'Angelo V, Granata C, Cavalcanti E, Maurea N, Maiolino P, Bianco F, Montano M, Silvestro L, Terranova Barberio M, Roca MS, Di Maio M, Marone P, Botti G, Petrillo A, Daniele G, Lastoria S, Iaffaioli VR, Romano G, Caraco C, Muto P, Gallo C, Perrone F, Budillon A. Phase 1/2 study of valproic acid and short-course radiotherapy plus capecitabine as preoperative treatment in low-moderate risk rectal cancer-V-shoRT-R3 (Valproic acid--short Radiotherapy--rectum 3rd trial). BMC Cancer. 2014 Nov 24;14:875. doi: 10.1186/1471-2407-14-875.

    PMID: 25421252DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Valproic AcidCapecitabine

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

Pentanoic AcidsValeratesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsFatty Acids, VolatileFatty AcidsLipidsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFluorouracilUracilPyrimidinonesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and Nucleosides

Study Officials

  • Antonio Avallone, M.D.

    National Cancer Institute, Naples

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Antonio Avallone, M.D.

CONTACT

+39 081 5903629avalloneantonio@libero.it

Maria Carmela Piccirillo, M.D.

CONTACT

+39 081 5903571marilina.piccirllo@usc-intnapoli.net

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 2, 2013

First Posted

July 12, 2013

Study Start

May 1, 2012

Primary Completion

November 1, 2023

Study Completion

April 1, 2024

Last Updated

March 24, 2023

Record last verified: 2023-03

Locations

IT(1)