Neo-adjuvant Chemoradiotherapy Using Infusional Gemcitabine Followed by Surgery for Locally Advanced Rectal Cancer

NCT ID: NCT02919878

Last Updated: 2018-08-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2019-12-31

Brief Summary

Phase II Study of Neo-adjuvant Chemoradiotherapy using infusional Gemcitabine followed by Surgery for Locally Advanced (T3 and T4 or Node positive) Rectal Adenocarcinoma.

Detailed Description

Results of neo-adjuvant chemo-radiation for advanced rectal cancer have plateaued with pathological complete response rates of 10-20% in spite of the addition of new cytotoxic agents and/ or molecular targeted therapies. The combination of 5-fluorouracil and radiation produces effective sensitization but further improvements require assessment of other sensitizers to increase the pathological complete response rates. Gemcitabine has been used in combination with radiation for several GI cancers but few studies have examined its role in rectal cancer. This study will examine a combination of Gemcitabine and radiation as neo-adjuvant therapy in advanced rectal cancer to increase the pathological complete response (pCR) rate from the investigators traditional 6% to > 40 %.

Conditions

Rectal Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

pre-op Gemcitabine & XRT

Pre-op chemo: Gemcitabine will be administered as continuous infusion IV over 24 hrs (100 mg/m2) weekly for 6 wks starting on day 1 of Radiotherapy (XRT).

XRT/ Intensity modulated radiotherapy(IMRT): 1.8 Gy/fx, 5 fractions/wk will be delivered. Pelvis will receive 45 Gy/25 fractions/5 wks with a boost dose of 5.4 Gy for T3 and 9 Gy for T4 to a cone down volume. The total tumor dose= 50.4 -54 Gy.

Post-op chemo: Standard 6 cycles of adjuvant Capecitabine (1250 mg/m2) PO twice per day on days 1-14 each cycle, (every 21 days) in patients who have a complete resection of rectal cancer and negative surgical margins.

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

Nucleoside analog- Chemotherapy

XRT

Intervention Type: RADIATION

pre-operative radiotherapy given concurrently with Gemcitabine chemotherapy

capecitabine

Intervention Type: DRUG

Capecitabine is given post operatively as adjuvant chemotherapy for 6 cycles. Each cycle consist of 2500 mg/m2 per day given orally from D1-14

Interventions

Gemcitabine

Nucleoside analog- Chemotherapy

Intervention Type: DRUG

XRT

pre-operative radiotherapy given concurrently with Gemcitabine chemotherapy

Intervention Type: RADIATION

capecitabine

Capecitabine is given post operatively as adjuvant chemotherapy for 6 cycles. Each cycle consist of 2500 mg/m2 per day given orally from D1-14

Intervention Type: DRUG

Other Intervention Names

Gemzar; External beam radiotherapy (XRT); Xeloda

Eligibility Criteria

Inclusion Criteria

1. Adenocarcinoma of the rectum without evidence of distant metastases

2. Patient must be 18 years of age or greater

3. Potentially resectable disease based upon surgeons evaluation

4. Clinical stages T3 or T4a, and/ or positive nodes based upon endorectal ultrasound and/ or MRI.

5. Absolute neutrophil count of > 1500 per microliter and platelet count > 100,000 per microliter; Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and alkaline phosphatase < 2.5 X upper limit of normal (ULN), bilirubin < = 1.5 ULN, calculated creatinine clearance > 50 ml/min using Cockcroft-Gault formula:

Male: Creatinine Clearance = (140 - age) x weight/(72 X serum creatinine) Female: Creatinine Clearance = (140 - age) x weight/(72 X serum creatinine x 0.85)

6. Eastern cooperative oncology group (ECOG) performance status 0-2

7. No history of other malignancies within 5 years, except non-melanoma skin cancer, in situ carcinoma of the cervix, or ductal carcinoma in situ of the breast. Previous invasive cancer permitted if disease free at least 5 years.

8. Signed study-specific informed consent prior to enrolment

Exclusion Criteria

1. Any evidence of distant metastasis

2. Synchronous primary colon carcinomas, except T1 lesions (full colonoscopy not required for enrollment)

3. Extension of malignant disease to the anal canal

4. Prior radiation therapy to the pelvis

5. Prior chemotherapy for malignancies

6. Pregnancy or lactation, (exclusion due to potential adverse effects of therapy). Women of childbearing potential with either a positive or no pregnancy test (serum or urine) at baseline. Women/men of childbearing potential not using a reliable and appropriate contraceptive method. (Postmenopausal women must have been amenorrheic for at least 12 months to be considered to be of non-childbearing potential.) Patients will agree to continue contraception for 30 days from the date of the last study drug administration.

7. Serious, uncontrolled, concurrent infection(s).

8. Participation in any investigational drug study within 4 weeks preceding the start of study treatment

9. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months.

10. Evidence of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake

11. Other serious uncontrolled medical conditions that the investigator feels might compromise study participation.

12. Major surgery within 4 weeks of the study treatment

13. Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome

14. Known, existing uncontrolled coagulopathy

15. No concurrent cimetidine allowed

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

King Faisal Specialist Hospital & Research Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shouki Bazarbashi, MD

Role: PRINCIPAL_INVESTIGATOR

KFSH&RC

Locations

Oncology Centre, King Faisal Specialist Hospital and Research Centre

Riyadh, , Saudi Arabia

Site Status: RECRUITING

Countries

Saudi Arabia

Central Contacts

Shouki Bazarbashi, MD

Role: CONTACT

bazarbashi@kfshrc.edu.sa

00966 11 442 3935

Fazal Hussain, MD

Role: CONTACT

fhussain@kfshrc.edu.sa

966-11-4423949

Facility Contacts

Shouk1 Bazarbashi, MD

Role: primary

bazarbashi@kfshrc.edu.sa

00966 11 442 3935

Fazal Hussain, MD

Role: backup

fhussain@kfshrc.edu.sa

966-11-4423949

References

Bazarbashi S, Elshenawy MA, Badran A, Aljubran A, Alzahrani A, Almanea H, Alsuhaibani A, Alashwah A, Neimatallah M, Abduljabbar A, Ashari L, Alhomoud S, Ghebeh H, Elhassan T, Alsanea N, Mohiuddin M. Neoadjuvant concurrent chemoradiotherapy using infusional gemcitabine in locally advanced rectal cancer: A phase II trial. Cancer Med. 2022 May;11(10):2056-2066. doi: 10.1002/cam4.4590. Epub 2022 Feb 10.

Reference Type: DERIVED

PMID: 35146939 (View on PubMed)

Other Identifiers

2141-124

Identifier Type: -

Identifier Source: org_study_id