Rosuvastatin in the Treatment of Rectal Cancer

NCT02569645 | Completed Phase 2

• 1 other identifier: OZM-064
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Rectal Cancer

Keywords

Rectal cancer; Rosuvastatin

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 3 years

Secondary Outcomes (17)

• To determine the Ro resection rate

  Up to 3 years

• To determine the pathological near-complete or complete tumour response rate

  Up to 3 years

• To determine the sphincter preservation rate

  Up to 3 years

• To determine the down staging rate

  Up to 3 years

• To determine 3-year disease free survival

  Up to 3 years

Study Arms (1)

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.

Drug: Rosuvastatin

Interventions

Rosuvastatin DRUG

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.

Also known as: Crestor

Single Arm - Rosuvastatin

Eligibility Criteria

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

You may qualify if:

• 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):
• a. 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• AHS Cancer Control Alberta: lead
• Ozmosis Research Inc.: collaborator

Study Sites (1)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jose Monzon, PhD MD FRCPC

  Tom Baker Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2015
• First Posted: October 7, 2015
• Study Start: November 1, 2015
• Primary Completion: September 24, 2021
• Study Completion: September 24, 2021
• Last Updated: July 20, 2022

Record last verified: 2022-07

Locations

CA (1)