IMPROVE Intervention Trial Implementing Non-invasive Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer (IMPROVE-IT)
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| ClinicalTrials.gov Identifier: NCT03748680 |
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Recruitment Status :
Recruiting
First Posted : November 21, 2018
Last Update Posted : February 25, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Colorectal Cancer Circulating Tumor DNA Adjuvant Chemotherapy Progression Free Survival | Drug: Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapy Other: Intensified Follow-up Schedule | Phase 2 |
The main clinical hypothesis is that patients having undergone radical resection from CRC do not present with detectable tumor DNA in the plasma, whereas patients with detectable tumor DNA two weeks' post surgery have residual microscopic disease, and consequently a high risk of diseases recurrence which can be prevented with adjuvant chemotherapy.
The primary aim of the present study is to investigate - in a randomized trial - if use of standard adjuvant chemotherapy therapy improves the disease free survival in patients with molecular biological residual disease where adjuvant chemotherapy is not standard treatment .
Secondary aims include investigating molecular biological response to adjuvant chemotherapy in patients with post-operative ctDNA.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 64 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | A open label 1:1 randomized phase II exploratory study |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Implementing Non-invasive Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer |
| Actual Study Start Date : | October 1, 2018 |
| Estimated Primary Completion Date : | October 1, 2023 |
| Estimated Study Completion Date : | October 1, 2025 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: A
Intensified follow-up schedule
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Other: Intensified Follow-up Schedule
Close monitoring with Imaging during follow-up Patients included in this trial will undergo intensified follow-up with CT-chest and abdomen every four months after surgery for the first 2 years, then every 6 months for 1 years and finally once yearly for the last 2 years up to 5 years follow-up is completed. |
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Experimental: B
Adjuvant chemotherapy + intensified follow-up schedule
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Drug: Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapy
Six months of adjuvant combination chemotherapy with Capox (or FOLFOX) Patients will receive adjuvant chemotherapy with eight cycles of CAPOX (oxaliplatin 130 mg/m2 day 1 and capecitabine 1000 mg/m2 b.i.d. days 1-14, repeated every 3 weeks. (Patients with an ileostomy are only eligible for FOLFOX and will be treated with 12 cycles of FOLFOX (oxaliplatin 85 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5FU 400 mg/m2 bolus day 1 and 5FU 2400 mg/ m2 over 46-48 hours day 1-3, repeated every second weeks) |
- DFS [ Time Frame: 3 years ]Disease free survival
- Molecular biological response [ Time Frame: 6 months ]Molecular biological response at 6 months
- MB-DFS [ Time Frame: 1 year ]Molecular biological disease free survival at 1 year
- TT-MBR [ Time Frame: 3 years ]Time to molecular biological recurrence
- TTR [ Time Frame: 3 years ]Time to radiological recurrence
- LRR [ Time Frame: 3 years ]Local recurrence rate
- DRR [ Time Frame: 3 years ]Distant recurrence rate
- OS [ Time Frame: 5 years ]Overall survival
- TR [ Time Frame: 3 years ]Translational research exploratory
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Surgically removed Adenocarcinoma of the colon or rectum
- Pathologically stage I or II disease, and radical resection
- Detectable ctDNA in two weeks postoperative plasma sample
- No indication for adjuvant chemotherapy according to DCCG guidelines (website)
- Age at least 18 years
- ECOG performance status 0-2
- Clinically eligible for adjuvant chemotherapy at investigators decision.
- Adequate bone marrow, liver and renal function allowing systemic chemotherapy (Absolute neutrophil count ≥1.5x109/l and thrombocytes ≥ 100x109/l. Bilirubin ≤ 1.5 x upper normal value and alanine aminotransferase ≤ 3 x upper normal value, and Calculated or measured renal glomerular filtration rate at least 30 mL/min)
- Anticonception for fertile women and for male patients with a fertile partner. Intrauterine device, vasectomy of a female subject's male partner or hormonal contraceptive are acceptable •
- Written and verbally informed consent
Exclusion Criteria:
- Radiological evidence of distant metastasis, by CT- chest and abdomen
- Incapacity, frailty, disability and comorbidity to a degree that according to the investigator is not compatible with combination chemotherapy
- Previous treatment with 5FU or oxaliplatin
- Neuropathy NCI grade > 1
- Other malignant tumor within 5 years except non-melanoma skin cancer or carcinoma in situ cervicis uteri
- Pregnant (positive pregnancy test) or breast feeding women
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03748680
| Contact: Karen-Lise G Spindler, Professor | 0045 7846 2535 ext +4578462535 | k.g.spindler@rm.dk | |
| Contact: Karen-Lise G Spindler, Professor | +4578462535 ext +4578462535 | k.g.spindler@rm.dk |
| Denmark | |
| Aalborg University Hospital | Recruiting |
| Aalborg, Denmark | |
| Aarhus University Hospital | Recruiting |
| Aarhus, Denmark, 8000 | |
| Contact: Karen-Lise G Spindler, Prof. +457846 2535 k.g.spindler@rm.dk | |
| Contact: Line M Sparvath, CRN 457846 2610 linspa@rm.dk | |
| Sub-Investigator: Søren Lauerberg, Prof. | |
| Sub-Investigator: Claus L Andersen, Prof. | |
| Herlev Hospital | Recruiting |
| Herlev, Denmark | |
| Odense University Hospital | Recruiting |
| Odense, Denmark | |
| Responsible Party: | Karen-Lise Garm Spindler, Professor, Aarhus University Hospital |
| ClinicalTrials.gov Identifier: | NCT03748680 |
| Other Study ID Numbers: |
KFE-1803 |
| First Posted: | November 21, 2018 Key Record Dates |
| Last Update Posted: | February 25, 2022 |
| Last Verified: | February 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases |
Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Oxaliplatin Antineoplastic Agents |