Temozolomide and irinotecan combination chemotherapy in patients with a specific subgroup of colorectal cancer and with circulating tumor DNA positivity after standard post-operative treatment

Phase 1

• Conditions: Stage II (pT4)/III colorectal cancer with positive circulating tumor DNA (ctDNA) after oxaliplatin-based adjuvant chemotherapy; MedDRA version: 21.0Level: LLTClassification code 10001170Term: Adenocarcinoma of colon stage IISystem Organ Class: 100000004864; MedDRA version: 21.0Level: LLTClassification code 10001171Term: Adenocarcinoma of colon stage IIISystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-005437-32-IT
• Lead Sponsor: FONDAZIONE IRCCS ISTITUTO NAZIONALE DEI TUMORI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-05-20
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

General Inclusion Criteria:
- Have provided written informed consent prior to any study specific procedures.
- Age = 18 years.
- Histologically confirmed diagnosis of stage III or T4N0 stage II colon cancer (located 12 cm from the anal verge by endoscopy and above the peritoneal reflection at surgery) or histologically confirmed diagnosis of locally-advanced resectable rectal cancer (proximal margin located at < 12 cm from the anal verge).
- Completion of radical surgery for patients with colon cancer and preoperative chemo-radiotherapy and radical surgery for patients with rectal cancer.
- Completion of at least 3 months of oxaliplatin-based (CAPOX or FOLFOX) adjuvant chemotherapy (or candidate to oxaliplatin-based adjuvant chemotherapy if post-surgery pre-screening).

Molecular Pre-screening Inclusion Criteria
- Absent MGMT expression by IHC, MGMT promoter methylation by pyrosequencing (> 5%) and MSS by standard assessment.
- Presence of ctDNA in the liquid biopsies collected at 2-6 weeks after the last dose of standard adjuvant chemotherapy.

Screening Inclusion Criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Completion of adjuvant chemotherapy for a duration of at least three months.
- Adequate organ function.
- Carcinoembryonic antigen (CEA) level = 10 ng/ml.
- No evidence of metastatic disease by chest and abdomen computed tomography (CT) scan.
- Male subjects with female partners of childbearing potential must be willing to use adequate contraception as approved by the investigator (barrier contraceptive measure or oral contraception).
- Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

General Exclusion Criteria
- History of another neoplastic disease, unless in remission for = 5 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- Microscopic or macroscopic evidence of residual tumor (R1 or R2 resections). Patients should never have had any evidence of metastatic disease (including presence of tumor cells in the peritoneal lavage).

Screening Exclusion Criteria:
- Inability to swallow pills.
- Active infection requiring intravenous antibiotics at the start of study treatment.
- Evidence of any other disease, neurologic or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of any of the study medications, puts the patient at higher risk for treatment-related complications or may affect the interpretation of study results.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
- Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. 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 (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment.
- Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents = 6 months prior to start of study treatment, myocardial infarction = 6 months prior to study enrolment, unstable angina, New York Heart Association (NYHA) Functional Classification Grade II or greater congestive heart failure, or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment.
- Previous treatment with temozolomide or irinotecan for any indication.
- Known presence of one of the following UGT1A1 1(TA)6/UGT1A1 36(TA)5; UGT1A1 28(TA)7/UGT1A1 37(TA)8 (homozygous genotype).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified