Colorectal CancerPhase 1/2V-shoRT-R3NCT01898104
Preoperative Valproic Acid and Radiation Therapy for Rectal Cancer
A Phase 1/2 study testing preoperative radiation therapy, Valproic Acid and Capecitabine in people with Colorectal Cancer, run by National Cancer Institute, Naples at 1 site in Italy.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- preoperative radiation therapy, Valproic Acid and Capecitabine
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 152 participants
- Where
- 1 siteItaly
- Study dates
- May 2012to Apr 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Istituto Nazionale Tumori Fondazione G. Pascale
Naples
About this study
Official title: Phase 1/2 Study of Valproic Acid and Short-course Radiotherapy Plus Capecitabine as preoperatIve Treatment in Low-moderate Risk Rectal Cancer
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.
- Conditions
- Colorectal Cancer
- Being tested
- preoperative radiation therapy, Valproic Acid, Capecitabine
- Keywords
- rectal, low risk, moderate risk
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
preoperative radiation therapyRadiation
25 Gy in 5 fractions over 1 week
Valproic AcidDrug
CapecitabineDrug
| Study group | Role | What they receive |
|---|---|---|
| SCRT | Active comparator | short course radiotherapy (SCRT) alone 25 Gy in 5 fractions over one week. Receives: Radiation: preoperative radiation therapy |
| V-SCRT | Active comparator | Valproic acid (V) + short course radiotherapy Receives: Radiation: preoperative radiation therapy; Drug: Valproic Acid |
| C-SCRT | Active comparator | capecitabine (C) + short course radiotherapy Receives: Radiation: preoperative radiation therapy; Drug: Capecitabine |
| VC-SCRT | Active comparator | valproic acid + capecitabine + short course radiotherapy Receives: Radiation: preoperative radiation therapy; Drug: Valproic Acid; Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
maximum tolerated dose of capecitabine, given alone or in combination with valproic acid
Phase 1 primary objective
Measured: 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
Measured: 8 weeks
Secondary outcomes (4)
overall survival
Measured: 1 year
number of patients alive with disease progression
Measured: one year
number of patients with pathologic complete response
Measured: 2 months
changes in quality of life from baseline
Measured: up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2013 (estimated)
- Study startMay 2012
- Primary completionNov 2023 (estimated)
- Study completionApr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 152 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute, Naples
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Antonio Avallone, M.D., Principal investigator, National Cancer Institute, Naples
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01898104
- Sponsor's protocol ID
- V-shoRT-R3
- Other IDs
- 2012-002831-28
- Acronym
- V-shoRT-R3
- Status last verified
- Mar 2023
- First submitted
- 2 Jul 2013
- Last updated
- 24 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 25421252
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Study of Valproic Acid and Short-course Radiotherapy Plus Capecitabine as preoperatIve Treatment in Low-moderate Risk Rectal Cancer
- ClinicalTrials.gov ID
- NCT01898104
- Acronym / sponsor ID
- V-shoRT-R3 / V-shoRT-R3
- Conditions
- Colorectal Cancer
- Keywords
- rectal, low risk, moderate risk
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 152 participants (estimated)
- Lead sponsor
- National Cancer Institute, NaplesUniversity, hospital or other
- Study start
- May 2012
- Primary completion
- Nov 2023 (estimated)
- Study completion
- Apr 2024 (estimated)
- First posted
- 12 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| SCRT | Active comparator | Radiation: preoperative radiation therapyshort course radiotherapy (SCRT) alone 25 Gy in 5 fractions over one week. |
| V-SCRT | Active comparator | Radiation: preoperative radiation therapy, Drug: Valproic AcidValproic acid (V) + short course radiotherapy |
| C-SCRT | Active comparator | Radiation: preoperative radiation therapy, Drug: Capecitabinecapecitabine (C) + short course radiotherapy |
| VC-SCRT | Active comparator | Radiation: preoperative radiation therapy, Drug: Valproic Acid, Drug: Capecitabinevalproic acid + capecitabine + short course radiotherapy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (23 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| preoperative radiation therapy25 Gy in 5 fractions over 1 week | Radiation | C-SCRT, SCRT, V-SCRT, VC-SCRT |
| Valproic Acid | Drug | V-SCRT, VC-SCRT |
| Capecitabine | Drug | C-SCRT, VC-SCRT |
Primary outcome
maximum tolerated dose of capecitabine, given alone or in combination with valproic acid
Time frame: up to 3 weeks
Phase 1 primary objective
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
4 secondary outcomes
overall survival
Time frame: 1 year
number of patients alive with disease progression
Time frame: one year
number of patients with pathologic complete response
Time frame: 2 months
changes in quality of life from baseline
Time frame: up to 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2023.
- Derived from this study: PubMed 25421252Avallone 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Avallone, M.D. principal investigator
National Cancer Institute, Naples
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing preoperative radiation therapy, Valproic Acid and Capecitabine in people with Colorectal Cancer, run by National Cancer Institute, Naples at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Antonio Avallone, M.D. (+39 081 5903629, avalloneantonio@libero.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
maximum tolerated dose of capecitabine, given alone or in combination with valproic acid (time frame: up to 3 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01898104, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2023; AzTrials last refreshed its copy on 7 Nov 2026.