Carboplatin-cyclophosphamide Combined With Atezolizumab

NCT02914470 | Completed Phase 1 DMC

• 1 other identifier: N16LOG
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single centre, 3+3, dose finding, open label, phase 1b clinical study of carboplatin and cyclophosphamide, in combination with atezolizumab.

Conditions

Breast Cancer; Cervix Cancer; Ovarian Cancer; Endometrial Cancer

Keywords

advanced

Outcome Measures

Primary Outcomes (1)

• Toxicity; Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03

  Adverse events will be graded according to NCI Common Toxicity Criteria version 4.03

  up to 30 days after end of treatment

Secondary Outcomes (1)

• Overall Response Rate

  assessed up to 120 months

Study Arms (1)

carbo, cyclo, atezolizumab

EXPERIMENTAL

The starting dose is carboplatin AUC 5mg/ml\*min (d1), cyclophosphamide 600mg/m2(d1) and atezolizumab 840 mg (D1, 15), all administered intravenously

Drug: carbplatin, cyclophophamide, atezolizumab

Interventions

carbplatin, cyclophophamide, atezolizumab DRUG

carbo, cyclo, atezolizumab

Eligibility Criteria

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

You may qualify if:

• Histological or cytological proof of advanced breast cancer (M1) or advanced gynaecological cancer (cervix (M1, FIGO IVA/IVB), ovarian (only after recurrence on carboplatin and/or paclitaxel) stage 4 cervical or endometrial (T3-T4, FIGO IVA/IVB) cancer) pre-treated with maximally one line of systemic chemotherapy in the advanced setting and any line of hormonal therapy for advanced disease and potentially benefitting from carboplatin-cyclophosphamide and atezolizumab. (prior (neo-)adjuvant chemotherapy is accepted and does not count as one line, since administered in early stage disease);
• Men and women \>= 18 years;
• Able and willing to give written informed consent;
• WHO performance status of 0 or 1;
• Life expectancy \>= 3 months, allowing adequate follow up of toxicity evaluation and antitumor activity;
• Minimal acceptable safety laboratory values

You may not qualify if:

• Any treatment with investigational drugs within 28 days prior to receiving the first dose of investigational treatment; or 21 days for standard (neo-)adjuvant chemotherapy, hormonal and immunotherapy;
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease;
• Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies.
• Women who have a positive pregnancy test (urine or serum) and/or who ware breast feeding;
• Unreliable contraceptive methods. Women and men enrolled in this trial must agree to use a reliable contraceptive method throughout the study (adequate contraceptive methods are: oral, injected or implanted hormonal methods, intra-uterine devices or systems, condom or other barrier contraceptive measures, sterilization and true abstinence);
• Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients;
• Positive test for HIV
• Active hepatitis B (defined as having a positive hepatitis B surface antigen \[HbsAg\] test at screening) or active hepatitis C Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible.
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RN
• Active tuberculosis
• Receipt of a live, attenuated vaccine within 28 days prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4 (like Ipilimumab), anti-PD-1 (like pemprolizumab), or anti-PD-L1 therapeutic antibodies (like atezolizumab).
• Treatment with systemic immunostimulatory agents (including but not limited to interferons or IL-2) within 28 days or five half-lives of the drug (whichever is shorter) prior to enrolment;
• Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] agents) within 28 days prior to enrolment, or anticipated requirement for systemic immunosuppressive medications during the trial
• Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., one-time dose of dexamethasone for nausea) may be enrolled in the study. The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed;

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Roche Pharma AG: collaborator

Study Sites (1)

Antoni van Leeuwenhoek

Amsterdam, Netherlands

Location

MeSH Terms

Conditions

Breast Neoplasms; Uterine Cervical Neoplasms; Ovarian Neoplasms; Endometrial Neoplasms

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2016
• First Posted: September 26, 2016
• Study Start: January 1, 2017
• Primary Completion: August 1, 2017
• Study Completion: October 1, 2021
• Last Updated: October 19, 2021

Record last verified: 2021-10

Locations

NL (1)