Phase II Trial of Nab-Paclitaxel as First Line Cytotoxic Chemotherapy in Patients With Unresectable and Metastatic Cutaneous Squamous Cell Carcinoma
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Response Rate
Study Overview
Brief Summary
This is an investigator initiated phase II study to assess the efficacy of a chemotherapy called nab-paclitaxel as first line cytotoxic chemotherapy in subjects with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (SCC). All subjects receive the treatment by vein weekly and receive the same dose of the treatment.
The risk of developing cutaneous SCC is approximately 10% in a lifetime. The vast majority are treated surgically and do not recur. However a small percentage become unresectable over time or metastasize distantly in the body. Unresectable and metastatic cutaneous SCC has a poor prognosis and oncologists often choose a whole body therapy without the benefit of prospective efficacy data. Very little prospective investigation into the efficacy of specific chemotherapy regimens as a function of line of therapy has been performed in this patient population. Nab-paclitaxel is type of chemotherapy that has demonstrated activity in other types of cancer such as lung and head and neck cancers. The primary objective of this study is to determine the response rate (percentage of subjects with tumor shrinkage) to nab-paclitaxel treatment in subjects with cutaneous SCC who have not received cytotoxic chemotherapy in the unresectable or the metastatic settings.. Secondary objectives are the progression free survival (time until tumor starts to grow), safety, assessment of the percentage of subjects whose tumor expresses a protein called SPARC, and correlating the expression of SPARC with response to treatment. To determine if the tumor expresses SPARC part of a prior standard biopsy such as that performed to establish the diagnosis of SCC will be used. SPARC is a protein that is overexpressed in a range of different cancer types and may alter the environment around the tumor possibly in a way that may make the SCC more responsive to treatment with nab-paclitaxel.
Detailed Description
Non-melanoma skin cancers represent the most common type of cancer in the United States with cutaneous SCC comprising 20% of these malignancies. The risk of developing cutaneous SCC is approximately 10% in a lifetime. This risk increases with age and varies according to the latitude in which one lives. The incidence rate in the United States is increasing as a result of multiple factors including altered sun exposure patterns and population aging. Early detection is critical as the vast majority are cured by definitive localized therapy with an overall 5-year cure rate of greater than 90%.
Although the vast majority of cutaneous SCCs are treated surgically with curative intent the estimated case fatality rate ranges from 1-5% depending on reported study. If regional lymph nodes are involved a standard treatment approach is lymphadenectomy followed by the consideration of adjuvant therapy (radiation +/- chemotherapy). However a subset of these patients ultimately will develop unresectable or distantly metastatic recurrences.
Unresectable SCC is treated using systemic approaches usually encompassing cytotoxic chemotherapy. However clinical investigation to determine efficacy of specific agents has been very limited and not studied in a rigorous fashion. Efficacy data stems largely from case reports and limited case series and from a very small number of phase II trials. As for targeted therapies, treatment with cetuximab demonstrated limited activity (RR 11%) in a 36 patient phase II trial. Many oncologists tend to treat with platinum agents, taxanes and 5-FU based regimens. However no standard exists. As such there is a need to explore more systematically the efficacy of specific chemotherapeutic agents with the goal of developing a standard treatment approach.
Nab-paclitaxel is an intriguing option to use for treatment given demonstrated efficacy in other malignancies with SCC histology. In clinical practice many oncologists use paclitaxel despite the lack of rigorous clinical investigation. The use of paclitaxel is limited by toxicities associated with the solvent Cermaphor EL.
Nab-paclitaxel is an albumin bound form of paclitaxel. In other malignancies such as breast cancer nab-paclitaxel is associated with improved response rates and time to progression relative to paclitaxel. Nab-paclitaxel based chemotherapy has demonstrated efficacy in other malignancies with SCC histology including head and neck carcinoma and NSCLC.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically confirmed unresectable locoregional or distantly metastatic squamous cell carcinoma arising from a cutaneous surface, lip, or ear. Basosquamous histology is eligible.
- •ECOG PS 0 or 1
- •Life expectancy of more than 4 months
- •Adequate renal, hepatic, and bone marrow function:
- •Patients must have adequate liver function: AST and ALT < 2.5 X upper limit of normal, alkaline phosphatase < 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis, Bilirubin < 1.5 mg/dL
- •Patients must have adequate bone marrow function: Platelets >100,000 cells/mm3, Hemoglobin > 9.0g/dL, WBC > 3,000 cells/mm3, and ANC > 1,500 cells/mm3
- •Patients must have adequate renal function: creatinine <1.5 mg/dL
- •Age > 18 years old
- •Women of childbearing potential and sexually active males must agree to use effective contraception during treatment and for three months after completing treatment
- •Negative serum or urine B-hCG pregnancy test at screening for patients of childbearing potential
- •No previous or concurrent malignancy except inactive nonmelanoma skin cancer, in situ carcinoma of the cervix, treated grade 1 papillary bladder cancer, localized prostate cancer detected via biopsy only and being treated with "watchful waiting", or other cancers where the patient has no evidence of recurrence for more than 5 years
- •Must be at least 28 days since surgical procedure and/or radiation therapy and at least 4 weeks since last treatment with targeted therapies such as cetuximab or immunotherapy.
- •No significant inter-current illness such as serious infection requiring intravenous antibiotics.
- •Patients must have < Grade 2 pre-existing peripheral neuropathy (per CTCAE v4.0)
- •Ability to provide informed consent
Exclusion Criteria
- •Prior systemic cytotoxic chemotherapy for unresectable SCC. Prior adjuvant or neoadjuvant cytotoxic chemotherapy provided not within prior 28 days is allowed. Prior systemic therapies with a targeted agent (cetuximab) or immunotherapy in the setting of unresectable SCC (is allowed).
- •Prior taxane based chemotherapy
- •The presence of any CNS tumor that has not been stable for at least 3 months off of corticosteroids and confirmed by imaging.
- •Prior major organ transplant or autoimmune disease requiring chronic immunosuppression
- •Psychiatric illness or social situation that would preclude compliance.
- •Active or chronic infection with HIV, hepatitis B or hepatitis C. Formal testing should be performed if clinical suspicion.
- •Patients with New York Heart Association class II, III, or IV disease or arrhythmia requiring treatment (rate controlled Atrial fibrillation is allowed)
- •Lack of measurable disease on imaging studies as defined by RECIST
- •Any condition that in the opinion of the treating physician is likely to prevent the patient from complying with any aspect of the protocol or that may put the patient at unacceptable risk
- •Known allergy to treatment medication
Arms & Interventions
nab-paclitaxel
weekly dosed nab-paclitaxel chemotherapy (days 1, 8 , 15 of a 28 day cycle) administered as an I.V. infusion over approximately 30 minutes. Dosage is determined by weight and height of participant.
Intervention: nab-paclitaxel (Drug)
Outcomes
Primary Outcomes
Response Rate
Time Frame: at week 8 post treatment
the percentage of subjects who develop Complete Response (CR) or Partial Response (PR)
Secondary Outcomes
- Prevalence of SPARC Expression(at baseline)
- Median Progression Free Survival(average 5 years)
- Treatment Response(at week 8 post treatment)
- Safety and Tolerability(up to 5 years)
Investigators
Philip Friedlander
Assistant Professor of Medicine
Icahn School of Medicine at Mount Sinai