Phase I study of S 95005 in combination with oxaliplatin in metastatic colorectal cancer

Phase 1

Completed

• Conditions: Metastatic colorectal cancer; Cancer; Colorectal cancer

• Registration Number: ISRCTN15566373
• Lead Sponsor: Servier (France)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-03-02
• Study Completion: 2020-04-09
• Last Update Posted: 5 July 2021

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

Inclusion criteria as of 24/11/2016:
1. Age 18 years or older
2. Histologically confirmed metastatic colorectal cancer pretreated by at least one line of standard chemotherapy
3. Restaging scan within 28 days before the first study drug intake
4. During the dose-escalation part, patient must have at least one evaluable or measurable metastatic lesion; and during the expansion part, patient must have at least one measurable metastatic lesion
5. Life expectancy of more than 3 months
6. Performance status Eastern Cooperative Oncology Group (ECOG): 0-1
7. Adequate bone marrow, liver, and kidney function
8. For patient who will receive bevacizumab: coagulation parameters in normal limit or in therapeutic limit for patients treated with anticoagulant
9. Women of childbearing potential must have a negative pregnancy test. Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use highly effective birth control method. Women and female partners using hormonal contraceptive must also use a barrier method.
10. Capacity to take oral tablet(s) without difficulty
11. Has provided written informed consent
12. Is willing and able to comply with scheduled visits and study procedures

Added 06/04/2017: For patients who will receive nivolumab: patients eligible for tumour biopsy and who agree to have two sequential biopsies during the study

Original inclusion criteria:
1. Age 18 years or older
2. Histologically confirmed metastatic colorectal cancer pretreated by at least one line of standard chemotherapy and naïve to oxaliplatin in the metastatic setting
3. Restaging scan within 28 days before the first study drug intake
4. During the dose-escalation part, patient must have at least one evaluable or measurable metastatic lesion; and during the expansion part, patient must have at least one measurable metastatic lesion
5. Life expectancy of more than 3 months
6. Performance status Eastern Cooperative Oncology Group (ECOG): 0-1
7. Adequate bone marrow, liver, and kidney function
8. For patient who will receive bevacizumab: coagulation parameters in normal limit and adequate proteinuria
9. Women of childbearing potential must have a negative pregnancy test
Both males and females must agree to use effective birth control method
10. Capacity to take oral tablet(s) without difficulty
11. Has provided written informed consent
12. Is willing and able to comply with scheduled visits and study procedures

Exclusion Criteria

Exclusion criteria as of 05/04/2017:
1. Grade 2 or higher peripheral neuropathy
2. During expansion part, patients who had recurrence during or within 6 months of completion of the adjuvant chemotherapy with oxaliplatin
3. Patients with brain metastases or leptomeningeal metastasis
4. Other active malignancy within the last 3 years (except for basal cell carcinoma or a non-invasive/in situ cervical cancer)
5. Has had certain other recent treatment e.g. major surgery, field radiation, participation in another interventional study within the specified time frames prior to study drug administration
6. For patient who will receive bevacizumab: history of allergic reactions/hypersensitivity to bevacizumab to any components used in the formulation, to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies.
7. Grade 3 or higher hypersensitivity reaction to oxaliplatin, or grade 1-2 hypersensitivity reaction to oxaliplatin not controlled with premedication
8. Patient previously treated by S 95005 or history of allergic reactions attributed to compounds of similar or biologic composition to S 95005 or any of its excipient, or has rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
9. Certain serious illnesses or serious medical conditions
10. Any condition that, in the judgment of the Investigator, may affect the patient's ability to understand and sign the informed consent and fully comply with all study procedure
11. Pregnancy or breast feeding
12. For patients planned to receive nivolumab:
12.1. Patients with active autoimmune disease or history of clinically severe autoimmune disease.
12.2. Patients with a condition requiring systemic treatment with either corticosteroids (> 20 mg daily prednisone equivalent) or other immunosuppressive medications within the specified time frames prior to first study drugs intake.
12.3. Prior treatment with anti-PD-1, anti-PD-L1, anti-programmed cell death ligand-2, anti-CD137, anti-OX-40, anti-CD40, anti-cytotoxic T lymphocyte-associated antigen-4 antibodies (CTLA-4), or any other immune checkpoint inhibitors.
12.4. Prior events of immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis and renal dysfunction, immune-mediated rash, immune-mediated encephalitis.
12.5. Allergic reactions/hypersensitivity to nivolumab or any components used in its formulation or previous severe hypersensitivity reaction to treatment with another monoclonal antibody.
12.6. Has a known history of active tuberculosis (Bacillus Tuberculosis).

Exclusion criteria as of 24/11/2016:
1. Grade 2 or higher peripheral neuropathy
2. During expansion part, patients who had recurrence during or within 6 months of completion of the adjuvant chemotherapy with oxaliplatin
3. Patients with brain metastases or leptomeningeal metastasis
4. Other active malignancy within the last 3 years (except for basal cell carcinoma or a non-invasive/in situ cervical cancer)
5. Has had

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> 1. Maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of S95005 when given in combination with oxaliplatin, during the first two cycles in the dose-escalation part<br> 2. Safety tolerance profile of S 95005 given in combination with oxaliplatin, at each visit, from the informed consent signature to the withdrawal visit, assessed by: adverse events, physical examinations and ECOG performance status, laboratory examinations (haematology, biochemistry and urinalysis), vital signs, ECG and body weight<br>