Rectal CancerPhase 2NCT02569645
Rosuvastatin in the Treatment of Rectal Cancer
A Phase 2 study testing Rosuvastatin in people with Rectal Cancer, run by AHS Cancer Control Alberta at 1 site in Canada.
Trial summary
This study will evaluate whether the addition of Rosuvastatin to standard chemoradiation therapy for the treatment of locally advanced rectal cancer may improve the pathological response rate and survival compared to standard chemoradiation therapy alone. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Rosuvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2015to 24 Sep 2021
- Phase
- Phase 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical stage 2-3 rectal adenocarcinoma, cT3/4N0/M0 or Tx N1-2/M0, within 5 cm of anal verge or less than 12cm from anal verge and threatened circumferential resection margin (≤3mm). Patients must have histological confirmation of rectal adenocarcinoma prior to registration.
- Patients must be 18 years or older.
- Able to swallow oral medication.
- Previous surgery, not for primary treatment of current rectal cancer, is permitted provided that wound healing has occurred and at least 14 days have elapsed prior to registration if surgery was major.
- ECOG 2 or less.
- Laboratory Requirements (must be done within 7 days prior to registration):
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- Hematology: i. Hemoglobin ≥90 g/L ii. Granulocytes (AGC) ≥ 1.5 x 109/L iii. Platelets ≥ 100 x 109/L b. Chemistry: i. Bilirubin ≤1.5 x UNL ii. ALT or AST ≤ 1.5 x UNL iii. Proteinuria ≤ grade 1 iv. Thyroid function within normal limits (TSH or free T4 within normal limits after correction) v. CPKs ≤ ULN, vi. Urinary myoglobin within normal limits Note: If serum creatinine is abnormal, a creatinine clearance should be calculated and be ≥ 60 ml/min.
- Women must be post-menopausal, surgically sterile or use two reliable forms of contraception if of child-bearing potential. Women of childbearing potential must have a urine pregnancy test taken and proven negative within 7 days prior to registration. Men must be surgically sterile or use an effective barrier method of contraception if sexually active with a woman of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose.
- Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements. It will be the responsibility of the local participating investigators to obtain the necessary local clearance. The patient must sign the consent form prior to registration. The consent form for this study must contain a statement, which gives permission for the sponsor and monitoring agencies to review patient records.
- Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 1⁄2 hours driving distance) placed on patients being considered for this trial. Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
Who cannot join
- Patients of Asian ethnicity (having Filipino, Chinese, Japanese, Korean, Vietnamese, or South Asian origin) will be excluded due to increased risk of toxicity.
- Previous and concurrent, experimental, chemotherapy, or radiotherapy treatment for primary rectal carcinoma.
- Statin exposure in the last 5 years.
- Known evidence of distant metastatic disease on staging investigation, including a CT of the chest, abdomen, and pelvis performed within 6 weeks prior to registration.
- Known history of previous malignancy, except adequately treated non-melanoma skin cancer or other solid tumour treated curatively with no evidence of disease for >5 years.
- Patients with malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease significantly affecting gastrointestinal (GI) function.
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- Patients with a known history of documented upper GI bleeding or upper GI ulcerative disease.
- Patients with hyperlipidemia with clinical indication for statin therapy or other prescribed medication (determination of acceptable fasting lipid values should be in accordance with current dyslipidemia management guidelines).
- Patients with inadequately treated hypothyroidism, as determined by the investigator.
- Patients with a known history of myopathy or rhabdomyolysis.
- Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction.
- Deemed by the physician to be at low risk for recurrence.
- No other non-malignant systemic disease that would preclude rosuvastatin administration or prolonged follow-up.
- Concurrent chronic use of NSAIDs.
- Concurrent chronic drug therapy with cyclosporine, colchicine, coumarin anticoagulants, amiodarone, gemfibrozil, other lipid-lowering therapies (e.g., fibrates or niacin), lopinavir/ritonavir, azole antifungals, and macrolide antibiotics.
- Known personal or family history of hereditary neuromuscular disorders.
- Known previous history of muscular toxicity with another HMG-CoA reductase inhibitor.
- Known history of alcohol abuse.
- Any known condition that could affect absorption of study oral drugs (capecitabine and rosuvastatin).
- Known contraindication to statin.
- Pregnant or nursing.
- Patients with symptomatic inflammatory bowel disease.
- Patients with uncontrolled hypothyroidism.
- Patients with chronic liver or disease.
- Patients with unexplained elevated serum transaminases exceeding 3x ULN.
- Patients known to be suffering from infection with HIV, Tuberculosis, Hepatitis C or Hepatitis B.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 2 Trial of Rosuvastatin (Crestor®) Combined With Standard Chemoradiation Therapy in the Treatment of High-Risk Locally Advanced Rectal Cancer
This study will evaluate whether the addition of Rosuvastatin to standard chemoradiation therapy for the treatment of locally advanced rectal cancer may improve the pathological response rate and survival compared to standard chemoradiation therapy alone.
Read the detailed description
The standard treatment of locally advanced rectal cancer involves neoadjuvant chemoradiation therapy (CRT) followed by surgery and further adjuvant chemotherapy. The pathologic complete responses associated with neoadjuvant CRT are 10-20%. The prognosis of patients undergoing neoadjuvant CRT is associated to the extent of post-treatment tumour regression, the final primary tumour stage and presence of involved lymph nodes in the surgical specimen. This data suggests that treatments that enhance the pathological response may result in improvements in survival.
Overwhelming preclinical and clinical evidence suggests that statins demonstrate anticancer properties and sensitize cancer tissues and protects normal tissues to the effects of radiation. Hence, the investigators hypothesize that the addition of rosuvastatin to standard CRT for the treatment of locally advanced rectal cancer may improve the pathological response rate. This protocol describes an open-label single-arm phase 2 study designed to test this hypothesis. Moreover, this study will also identify genetic, serological, and pathological biomarkers that may be both prognostic and predictive of response and toxicity to treatment.
- Conditions
- Rectal Cancer
- Being tested
- Rosuvastatin
- Keywords
- Rectal cancer, Rosuvastatin
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RosuvastatinDrug
Also called Crestor
40 mg rosuvastatin orally once per day with or without food, swallowed whole (not chewed, crushed or divided) starting 2 weeks prior to the initiation of radiation therapy and stopped at 4 weeks after the completion of radiation. Total duration of Rosuvastatin is 11 weeks if 25 fractions of radiotherapy are given, or 12 weeks if 30 fractions of radiotherapy are given.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm - Rosuvastatin | Experimental | This is a single arm, of Rosuvastatin (Crestor®) 40 mg orally daily starting 2 weeks prior to the initiation of radiation at week 1 and stopped 4 weeks after the completion of radiation at the start of week 12 or 13, depending on whether 25 or 30 fractions of radiotherapy are given. Receives: Drug: Rosuvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the pathological complete response rate in patients with high-risk locally advanced rectal cancer treated with standard neo-adjuvant chemotherapy and radiation in combination with rosuvastatin.
The rate of post-surgical specimens that demonstrate absence of any residual invasive disease or Grade 4 (complete) histological regression using the Dworak classification.
Measured: Up to 3 years
Secondary outcomes (17)
To determine the Ro resection rate
The rate that the surgical margins are negative of any invasive disease.
Measured: Up to 3 years
To determine the pathological near-complete or complete tumour response rate
Grade 3 (near-complete) or 4 (complete) histological regression using the Dworak classification.
Measured: Up to 3 years
To determine the sphincter preservation rate
The proportion of patients that undergo a sphincter preservation surgery versus abdominoperineal resection.
Measured: Up to 3 years
To determine the down staging rate
Proportion of patients that have a down staging of the primary tumour and/or lymph nodes; i.e. comparison between cT/N and ypT/N
Measured: Up to 3 years
To determine 3-year disease free survival
The proportion of patients alive with no clinical, radiological, or pathological evidence of rectal cancer recurrence at 3 years, starting at the time treatment was initiated. This definition includes, recurrence or relapse of rectal cancers, second primary cancer or death as events
Measured: Up to 3 years
To determine 3-year overall survival
The proportion of patients alive at 3 years, starting at the time treatment was initiated.
Measured: Up to 3 years
To determine the neoadjuvant rectal cancer (NAR) score
A surrogate endpoint of overall survival following neoadjuvant rectal cancer therapy.
Measured: Up to 3 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
Measured: Up to 3 years
To identify the genetic biomarkers that may be both prognostic and predictive of response and toxicity to treatment.
BRAF and KRAS genetic testing. Direct exon sequencing.
Measured: up to 3 years
To identify serological biomarkers that may be both prognostic and predictive of response and toxicity to treatment.
Changes in the levels of HMG CoA reductase pathway metabolites (Mevalonate, Ubiquinone) will also be performed using pre- and post-treatment serological markers.
Measured: up to 3 years
To identify pathological biomarkers that may be both prognostic and predictive of response and toxicity to treatment.
IHC using pre- and post FFPE tumour tissue samples. (Ki67, phopsorylated AKT, HMG CoA reductase, GGPS1 and ApopTag, p21, p27 and rhoA)
Measured: up to 3 years
Tmax will be collected as pharmacokinetic data
Measured: up to 3 years
Cmax will be collected as pharmacokinetic data
Measured: up to 3 years
T1/2 will be collected as pharmacokinetic data
Measured: up to 3 years
Dose normalized Cmax will be collected as pharmacokinetic data
Measured: up to 3 years
Area under the curve (AUC) will be collected as pharmacokinetic data
Measured: up to 3 years
Dose normalized AUC will be collected as pharmacokinetic data
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2015 (estimated)
- Study startNov 2015
- Primary completion24 Sep 2021
- Study completion24 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- AHS Cancer Control Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- Ozmosis Research Inc.
- Responsible party
- Sponsor
- Investigators
- Jose Monzon, PhD MD FRCPC, Principal investigator, Tom Baker Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02569645
- Sponsor's protocol ID
- OZM-064
- Status last verified
- Jul 2022
- First submitted
- 24 Sep 2015
- Last updated
- 20 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Trial of Rosuvastatin (Crestor®) Combined With Standard Chemoradiation Therapy in the Treatment of High-Risk Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT02569645
- Acronym / sponsor ID
- OZM-064
- Conditions
- Rectal Cancer
- Keywords
- Rectal cancer, Rosuvastatin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- AHS Cancer Control AlbertaUniversity, hospital or other
- Collaborators
- Ozmosis Research Inc.
- Study start
- Nov 2015
- Primary completion
- 24 Sep 2021 (actual)
- Study completion
- 24 Sep 2021 (actual)
- First posted
- 7 Oct 2015 (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.
This study will evaluate whether the addition of Rosuvastatin to standard chemoradiation therapy for the treatment of locally advanced rectal cancer may improve the pathological response rate and survival compared to standard chemoradiation therapy alone.
Detailed description
The standard treatment of locally advanced rectal cancer involves neoadjuvant chemoradiation therapy (CRT) followed by surgery and further adjuvant chemotherapy. The pathologic complete responses associated with neoadjuvant CRT are 10-20%. The prognosis of patients undergoing neoadjuvant CRT is associated to the extent of post-treatment tumour regression, the final primary tumour stage and presence of involved lymph nodes in the surgical specimen. This data suggests that treatments that enhance the pathological response may result in improvements in survival.
Overwhelming preclinical and clinical evidence suggests that statins demonstrate anticancer properties and sensitize cancer tissues and protects normal tissues to the effects of radiation. Hence, the investigators hypothesize that the addition of rosuvastatin to standard CRT for the treatment of locally advanced rectal cancer may improve the pathological response rate. This protocol describes an open-label single-arm phase 2 study designed to test this hypothesis. Moreover, this study will also identify genetic, serological, and pathological biomarkers that may be both prognostic and predictive of response and toxicity to treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm - Rosuvastatin | Experimental | Drug: RosuvastatinThis is a single arm, of Rosuvastatin (Crestor®) 40 mg orally daily starting 2 weeks prior to the initiation of radiation at week 1 and stopped 4 weeks after the completion of radiation at the start of week 12 or 13, depending on whether 25 or 30 fractions of radiotherapy are given. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Clinical stage 2-3 rectal adenocarcinoma, cT3/4N0/M0 or Tx N1-2/M0, within 5 cm of anal verge or less than 12cm from anal verge and threatened circumferential resection margin (≤3mm). Patients must have histological confirmation of rectal adenocarcinoma prior to registration.
- Patients must be 18 years or older.
- Able to swallow oral medication.
- Previous surgery, not for primary treatment of current rectal cancer, is permitted provided that wound healing has occurred and at least 14 days have elapsed prior to registration if surgery was major.
- ECOG 2 or less.
Key exclusion criteria (26 listed)
- Patients of Asian ethnicity (having Filipino, Chinese, Japanese, Korean, Vietnamese, or South Asian origin) will be excluded due to increased risk of toxicity.
- Previous and concurrent, experimental, chemotherapy, or radiotherapy treatment for primary rectal carcinoma.
- Statin exposure in the last 5 years.
- Known evidence of distant metastatic disease on staging investigation, including a CT of the chest, abdomen, and pelvis performed within 6 weeks prior to registration.
- Known history of previous malignancy, except adequately treated non-melanoma skin cancer or other solid tumour treated curatively with no evidence of disease for >5 years.
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 |
|---|---|---|
| RosuvastatinAlso: Crestor40 mg rosuvastatin orally once per day with or without food, swallowed whole (not chewed, crushed or divided) starting 2 weeks prior to the initiation of radiation therapy and stopped at 4 weeks after the completion of radiation. Total duration of Rosuvastatin is 11 weeks if 25 fractions of radiotherapy are given, or 12 weeks if 30 fractions of radiotherapy are given. | Drug | Single Arm - Rosuvastatin |
Primary outcome
To determine the pathological complete response rate in patients with high-risk locally advanced rectal cancer treated with standard neo-adjuvant chemotherapy and radiation in combination with rosuvastatin.
Time frame: Up to 3 years
The rate of post-surgical specimens that demonstrate absence of any residual invasive disease or Grade 4 (complete) histological regression using the Dworak classification.
17 secondary outcomes
To determine the Ro resection rate
Time frame: Up to 3 years
To determine the pathological near-complete or complete tumour response rate
Time frame: Up to 3 years
To determine the sphincter preservation rate
Time frame: Up to 3 years
To determine the down staging rate
Time frame: Up to 3 years
To determine 3-year disease free survival
Time frame: Up to 3 years
To determine 3-year overall survival
Time frame: Up to 3 years
To determine the neoadjuvant rectal cancer (NAR) score
Time frame: Up to 3 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
Time frame: Up to 3 years
To identify the genetic biomarkers that may be both prognostic and predictive of response and toxicity to treatment.
Time frame: up to 3 years
To identify serological biomarkers that may be both prognostic and predictive of response and toxicity to treatment.
Time frame: up to 3 years
To identify pathological biomarkers that may be both prognostic and predictive of response and toxicity to treatment.
Time frame: up to 3 years
Tmax will be collected as pharmacokinetic data
Time frame: up to 3 years
Cmax will be collected as pharmacokinetic data
Time frame: up to 3 years
T1/2 will be collected as pharmacokinetic data
Time frame: up to 3 years
Dose normalized Cmax will be collected as pharmacokinetic data
Time frame: up to 3 years
Area under the curve (AUC) will be collected as pharmacokinetic data
Time frame: up to 3 years
Dose normalized AUC will be collected as pharmacokinetic data
Time frame: up to 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2022.
- Individual participant dataSharing planned: Undecided
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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.
Jose Monzon, PhD MD FRCPC principal investigator
Tom Baker Cancer Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rosuvastatin in people with Rectal Cancer, run by AHS Cancer Control Alberta at 1 site in Canada.
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 10 inclusion and 26 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: finished, as of the sponsor's last update on 20 Jul 2022. 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 Canada. 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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the pathological complete response rate in patients with high-risk locally advanced rectal cancer treated with standard neo-adjuvant chemotherapy and radiation in combination with rosuvastatin. (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Jul 2022.