Neoplasm, Gynecologic Clinical Trial
Official title:
Open, Non Controlled, Multicenter, First-in-Human Study for the Evaluation of the Safety, Pharmacokinetics and Preliminary Antitumor Activity of GM102 in Patients With Advanced Pretreated Gynecological Cancer
| NCT number | NCT02978755 |
| Other study ID # | C101 |
| Secondary ID | |
| Status | Completed |
| Phase | Phase 1 |
| First received | |
| Last updated | |
| Start date | June 2016 |
| Est. completion date | June 10, 2020 |
| Verified date | March 2022 |
| Source | GamaMabs Pharma |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
First in Human study, assessing the safety profile, the pharmacokinetics and preliminary antitumor activity of GM102, a new compound (a monoclonal antibody), in patients with previously treated gynecological cancers bearing the AMHRII (anti-mullerian Hormone Receptor II) receptor. The primary objective of the study is to determine the GM102 recommended dose.
| Status | Completed |
| Enrollment | 78 |
| Est. completion date | June 10, 2020 |
| Est. primary completion date | June 10, 2020 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Locally advanced, or metastatic recurrent gynecological cancer, for whom no standard alternative therapy is available, having received at least one line of therapy and expressing AMHRII on tumor cells. - If possible at least one lesion should be identified for 2 biopsies: a baseline biopsy and an under-treatment biopsy for AMHRII expression and GM102 pharmacodynamics evaluation. - Available tumor block or at least 10 slides from formalin-fixed paraffin-embedded (FFPE) archival tissue. - At least one measurable lesion by RECIST (Response Evaluation Criteria in Solid Tumors) on screening CT-scan. - Written Informed Consent forms. - Willing and able to comply with the trial requirements. - Covered by healthcare insurance in accordance with local requirements. For phase 1b, only patients with either Sex cord stromal tumors or epithelial ovarian cancer or cervix cancer will be eligible Exclusion Criteria: - Age < 18 years old. - Eastern Cooperative Oncology Group (ECOG) performance status > 1 - Life expectancy < 12 weeks. - Known or symptomatic brain metastasis (other than totally resected or previously irradiated and non-progressive/relapsing) or lepto-meningeal carcinomatosis. - Concurrent treatment with any other anticancer therapy. - Concurrent chronic corticosteroid treatment. - Known severe anaphylactic or other hypersensitivity reactions secondary to a prior exposure to human antibodies or to any protein product. - Washout period before treatment initiation: < 3 weeks or 5 times the half-life, whichever is shorter, for prior antitumor therapy (small molecules and/or antibody-drug conjugates, radiotherapy) or 6 weeks for monoclonal antibodies. - Any active concomitant malignancy. - Serious concomitant illness e.g. active infection requiring systemic antibiotic, antifungal or antiviral drug, or physical examination or laboratory abnormalities, that, in the opinion of the Investigator, would compromise protocol objectives. - Poor bone marrow reserve as defined by neutrophils < 1.0 x 10E9/L or haemoglobin < 9.0 g/dL or platelet count < 100 x 10E9/L. - Poor organ function as defined by any one of the following: left ventricular ejection fraction = 40%, serum creatinine > 1.5 x upper limit of normal (ULN), total bilirubin > 1.5 x ULN, AST and ALT> 2.5 x ULN in the absence of liver metastasis or > 5 x ULN in case of documented liver metastasis. - Non-resolution of any prior treatment related toxicity to < Grade 2, except for alopecia according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03. - Pregnancy or breastfeeding. - Patient with reproductive potential who do not agree to use an accepted effective method of contraception - investigator's judgment - during the study period and for at least 4 months following completion of study treatment. - Patient participating in another clinical trial investigating a treatment during the study and within 30 days prior to first study treatment administration. - Patient deprived of her liberty by a judicial or administrative decision, patient admitted to a hospital, social institution or who is under a measure of legal protection, patient hospitalized without consent or who is in an emergency situation. |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Institut Bordet | Brussels | |
| Belgium | UZ Leuven | Leuven | |
| France | CHU Besançon | Besançon | |
| France | Institut Bergonié | Bordeaux | |
| France | Centre Oscar Lambret | Lille | |
| France | Centre Leon Berard | Lyon | |
| France | Institut de cancerologie de Montpellier | Montpellier | |
| France | Institut de cancerologie de Lorraine | Nancy | |
| France | Institut Curie | Paris | |
| France | Institut Universitaire Cancer Toulouse - Oncopole | Toulouse | |
| France | Gustave Roussy | Villejuif | |
| United Kingdom | Royal Marsden Hospital | London |
| Lead Sponsor | Collaborator |
|---|---|
| GamaMabs Pharma |
Belgium, France, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Phase I part: incidence of Dose Limiting Toxicities (DLTs) | Number of patients in the DLT evaluable population experiencing at least one DLT | Four weeks | |
| Primary | Phase Ib part: incidence of Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events (TEAEs) at Recommended Phase 2 Dose (RP2D) | Number of patients with at least one AE | Through study completion, an average of 1 year | |
| Secondary | PK: Maximum Serum Concentration [Cmax] | Cycle 1 Day 1 pre-dose, Cycle 1 Day 1 End Of Infusion (EOI), Cycle 1 Day 1 EOI + 3 hours, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 8, Cycle 1 Day 15 pre-dose, Cycle 1 Day 15 EOI, Cycle 2 Day 1 pre-dose, Cycle 2 Day 1 EOI, Cycle 2 Day 15 pre-dose, Cycle 2 Day 15 EOI, Cycle 3 Day 1 pre-dose, Cycle 3 Day 1 EOI, Cycle 3 Day 15 pre-dose, Cycle 3 Day 15 EOI, Cycle 4 Day 1 pre-dose, Cycle 4 Day 1 EOI, Cycle 4 Day 15 pre-dose, Cycle 4 Day 15 EOI | up to 16 weeks | |
| Secondary | PK: Area Under the Curve [AUC] | Cycle 1 Day 1 pre-dose, Cycle 1 Day 1 End Of Infusion (EOI), Cycle 1 Day 1 EOI + 3 hours, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 8, Cycle 1 Day 15 pre-dose, Cycle 1 Day 15 EOI, Cycle 2 Day 1 pre-dose, Cycle 2 Day 1 EOI, Cycle 2 Day 15 pre-dose, Cycle 2 Day 15 EOI, Cycle 3 Day 1 pre-dose, Cycle 3 Day 1 EOI, Cycle 3 Day 15 pre-dose, Cycle 3 Day 15 EOI, Cycle 4 Day 1 pre-dose, Cycle 4 Day 1 EOI, Cycle 4 Day 15 pre-dose, Cycle 4 Day 15 EOI | up to 16 weeks | |
| Secondary | Response Rate using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 | Percentage of patients who achieved a Complete Response (CR) or a Partial Response (PR) based on RECIST version 1.1 | Through study completion | |
| Secondary | Clinical benefit rate | Percentage of patients achieving Complete Response (CR), Partial Response (PR) or Stable Disease (SD) superior to 3 months | up to 3 months | |
| Secondary | Duration of response | Duration of overall response in months for patients who achieved PR and/or CR | Through study completion | |
| Secondary | Time to progression (TTP) | Time from first dose received until objective tumor progression | Through study completion |