Phase Ib/II Study of the Tumour-targeting Human F16IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Paclitaxel in Patients With Advanced Solid Tumours
Overview
- Phase
- Phase 1
- Intervention
- F16IL2 in combination with paclitaxel
- Conditions
- Solid Tumor
- Sponsor
- Philogen S.p.A.
- Enrollment
- 48
- Locations
- 5
- Primary Endpoint
- To establish the maximum tolerated dose (MTD) and the recommended dose (RD) of F16IL2 when administered in combination with paclitaxel (Phase I).
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This Phase Ib/II study is an open label, multicenter study.
The study is divided in two parts:
Phase I: an open-label, dose escalation study of F16IL2 in combination with paclitaxel for patients with solid tumours, bladder cancer, breast cancer, metastatic melanoma, mesothelioma, NSCLC, prostate cancer and sarcoma amenable to taxane therapy.
Phase II: a prospective, single-arm, multicentre study of a fixed dose of F16IL2 in combination with paclitaxel, equivalent to stage 1 of the Simon two-stage phase II design, for patients with metastatic melanoma, breast cancer and NSCLC amenable to taxane therapy.
Detailed Description
Breast cancer is a major cause of cancer mortality, second only to lung cancer as a cause of cancer death in women. The five-year survival rate for localized breast cancer has increased from 80 percent in the 1950s to 98 percent today. However, the mortality rate in the most advanced forms remains unsatisfactory. Indeed, the extensive use of mammography within screening programs has led to cancers being detected earlier, when early treatments may be more effective. A greater understanding of the molecular biology and genetic expression of breast cancer has therefore led to new pre-surgical and post-surgical treatments, including hormone modulators and monoclonal antibodies. Many of these agents have led to decreased mortality and disease recurrence. F16 is a human recombinant antibody fragment in the scFv (single chain Fragment variable) format that is directed against tenascin C, an angiogenesis marker common to most solid tumors independent of the tumor type. ScFv(F16) selectively localizes in tumor tissues in animal models as demonstrated both histologically and during mechanistic studies involving mice transfected with orthotopic human tumours. IL2, the human cytokine interleukin-2, is a potent stimulator of the immune response. It has a central role in the regulation of T cell responses and effects on other immune cells such as natural killer cells, B cells, monocyte/macrophages and neutrophils (Smith, 1988). IL2 can induce tumor regression through its ability to stimulate a potent cell-mediated immune response in vivo (Rosenberg, 2000).
Investigators
Eligibility Criteria
Inclusion Criteria
- •For Phase I, cohorts 1 to 8, of the study:
- •For patient of Phase I cohort 1, i.e. those patients receiving F16IL2 alone, patients must not be amenable to therapy with paclitaxel/taxanes but must be considered by the Principal Investigator to be suitable candidates for F16IL2 therapy alone.
- •Histologically or cytologically confirmed solid cancer with/without evidence of locally advanced or metastatic disease.
- •For advanced solid cancer patients, patients may have received previous chemotherapy or radiation therapy, but they must be amenable for paclitaxel treatment according to the discretion of the principal investigator.
- •For Phase I, cohorts 9 onwards:
- •Histologically or cytologically confirmed bladder cancer, breast cancer, unresectable metastatic (stage IV) non-uveal melanoma, mesothelioma, NSCLC, prostate cancer or sarcoma.
- •Prior therapies for metastatic disease are allowed, but patients must be amenable for paclitaxel treatment according to the discretion of the principal investigator.
- •For breast cancer patients only: patients not suitable for trastuzumab therapy (i.e., no evidence of HER2-overexpressing disease, or trastuzumab therapy exhausted in HER2-overexpressing disease).
- •For Phase II of the study:
- •Histologically or cytologically confirmed breast cancer, unresectable metastatic (stage IV) non-uveal melanoma, or NSCLC.
Exclusion Criteria
- Not provided
Arms & Interventions
F16IL2 in combination with paclitaxel
Intervention: F16IL2 in combination with paclitaxel
Outcomes
Primary Outcomes
To establish the maximum tolerated dose (MTD) and the recommended dose (RD) of F16IL2 when administered in combination with paclitaxel (Phase I).
Time Frame: 28 days
Safety evaluations performed days 1 through 28, including AEs, SAEs and standard laboratory assessments graded according to the NCI-CTCAE, v3, will be used for determination of dose limiting toxicity (DLT).
To investigate the efficacy of F16IL2, in terms of objective response rate in combination with paclitaxel in metastatic melanoma, breast cancer and NSCLC patients amenable to taxane therapy (Phase II)
Time Frame: 8 weeks
The primary efficacy endpoint is the proportion of patients achieving a Tumour Response at week 8.
Secondary Outcomes
- Human anti-fusion protein antibodies(18 months)
- Antitumor activity(12 months)
- Investigate pharmacokinetics of F16IL2 and paclitaxel when given as a combination.(2 weeks)
- Assessment of median progression-free survival and median overall survival.(12 months)
- To investigate the safety and tolerability of F16IL2 and paclitaxel when given as a combination (Phase I/II).(8 weeks)