Weekly Doses of Cilengitide and Paclitaxel in Treating Patients With Advanced Solid Tumors That Cannot Be Removed by Surgery

NCT01276496 | Completed Phase 1

• 5 other identifiers: NCI-2013-00619U01CA069912MC09158335P30CA015083
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial studies the side effects and the best dose of cilengitide when given together with paclitaxel weekly in treating patients with solid tumors that have spread nearby or to other areas of the body and cannot be removed by surgery. Cilengitide may stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel, work in different ways to the stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cilengitide together with paclitaxel may kill more tumor cells.

Conditions

Adult Solid Neoplasm; Estrogen Receptor Negative; HER2/Neu Negative; Male Breast Carcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (19)

• Best response, defined to be complete response (CR) or partial response (PR) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).

  From start of the treatment until disease progression/recurrence, assessed up to 3 months

• Change in Cyr61 expression levels (Cohort II)

  At the end of each cycle, the percent change in serum Cyr61 expression from pre-treatment levels will be determined for each patient. For each patient, a times series plot of the percent change in serum Cyr61 expression from pre-treatment levels will be constructed and visually inspected for trends across time as well as for differences between those who respond to treatment (CR or PR by RECIST criteria) and those who do not.

  Baseline to up to 3 months

• Change in Cyr61 expression levels (Cohort II)

  A Wilcoxon rank sum test will be used to assess the percent change in Cyr61expression level after one cycle of treatment from pretreatment levels differs between those who progress within 120 days (within the first 6 cycles of treatment) and those who remain progression-free at least 120 days.

  Baseline to 21 days

• Incidence of grade 3+ adverse events, as graded using NCI CTCAE v 4.0

  The number and severity of grade 3+ adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population.

  Up to 3 months

• Incidence of hematologic toxicity, including thrombocytopenia, neutropenia, and leukopenia, evaluated via the ordinal CTC

  Assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  Up to 3 months

• Incidence of non-hematologic toxicity, evaluated via the ordinal Common Toxicity Criteria (CTC)

  Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  Up to 3 months

• MTD of cilengitide and paclitaxel, defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least 1/3 of patients as graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0

  3 weeks

• Number of all adverse events, graded according to the NCI CTCAE v4.0

  The number of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population.

  Up to 3 months

• Overall survival (OS) (Cohort II)

  Kaplan-Meier method will be used to estimate the distribution of OS time.

  The time of registration to death due to any cause, assessed up to 3 months

• Progression-free survival (PFS) (Cohort II)

  Kaplan-Meier method will be used to estimate the distribution of PFS time.

  The time of registration to documentation of disease event where a disease event is local/regional/distant progression, contralateral breast disease, second primary disease or death due to any cause, assessed up to 3 months

• Response rate, defined as the proportion of patients whose tumor responds to treatment (Cohort II)

  Calculated as the number of eligible patients whose tumor meets the criteria for a CR or PR on two consecutive evaluations at least 6 weeks apart divided by the number of eligible patients with metastatic breast cancer refractory to taxanes who begin treatment. A 95% binomial confidence interval will be constructed for the true response rate.

  Up to 3 months

• Severity of all adverse events, graded according to NCI CTCAE v4.0

  The severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population.

  Up to 3 months

• Time to progression

  Up to 3 months

• Time to treatment failure

  Time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months

• Time until any treatment related toxicity

  Up to 3 months

• Time until hematologic nadir for ANC

  Up to 3 months

• Time until hematologic nadir for platelets

  Up to 3 months

• Time until hematologic nadir for WBC

  Up to 3 months

• Time until treatment related grade 3+ toxicity

  Up to 3 months

Secondary Outcomes (1)

• Incidence of toxicity, as assessed using PRO-CTCAE

  Up to 3 months

Other Outcomes (2)

• Pharmacokinetic (PK) parameters of cilengitide, including area under curve (AUC), maximum concentration Cmax and trough plasma concentrations

  Baseline; 1, 1.5, 2, 3, 4, and 5 hours post-cilengitide day 1 of courses 1 and 2; 27 hours post-paclitaxel day 2 of courses 1 and 2

• PK parameters of paclitaxel, including AUC, Cmax and trough plasma concentrations

  Baseline; 1, 1.5, 2, 3, 4, and 5 hours post-cilengitide day 1 of courses 1 and 2; 27 hours post-paclitaxel day 2 of courses 1 and 2

Study Arms (1)

Treatment (cilengitide, paclitaxel)

EXPERIMENTAL

Patients receive cilengitide IV over 1 hour on days\* 1, 8, and 15 and paclitaxel IV over 1 hour on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. NOTE: \*Some patients receive cilengitide IV over 1 hour on days 1, 2, 8, 9, 15, and 16.

Drug: Cilengitide; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Pharmacological Study

Interventions

Cilengitide DRUG

Given IV

Also known as: EMD 121974, EMD-121974

Treatment (cilengitide, paclitaxel)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cilengitide, paclitaxel)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (cilengitide, paclitaxel)

Pharmacological Study OTHER

Correlative studies

Treatment (cilengitide, paclitaxel)

Eligibility Criteria

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

You may qualify if:

• Histologic proof of cancer that is now unresectable (solid tumors, excluding lymphoma)
• For Cohort II only:
• Histologic adenocarcinoma of the breast with manifestations of metastatic cancer or locally advanced, unresectable cancer
• Estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) receptor negative disease per local standards
• Refractory to taxanes which is defined as one of the following:
• Having relapsed during or within 12 months of completing adjuvant paclitaxel or docetaxel
• Disease progression while on any taxane in the locally advanced, unresectable or metastatic breast cancer setting
• Ability and willingness to undergo biopsy for biomarker testing prior to start of treatment
• Disease must be measurable by imaging-based evaluation per Response Evaluation Criteria in Solid Tumors (RECIST) criteria (v1.1)
• Up to 5 prior regimens of chemotherapy for metastatic disease are allowed
• Absolute neutrophil count (ANC) \>= 1500/μL
• Hemoglobin (Hgb) \>= 9 g/dL
• Platelets (PLT) \>= 100,000/μL
• Total bilirubin =\< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) =\< 3 x ULN or AST =\< 5 x ULN if liver involvement

You may not qualify if:

• Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Any of the following prior therapies:
• Chemotherapy =\< 21 days prior to registration
• Mitomycin C/nitrosoureas =\< 42 days prior to registration
• Immunotherapy =\< 14 days prior to registration
• Biologic therapy =\< 14 days prior to registration
• Prior investigational therapy =\< 28 days prior to registration
• Full field radiation therapy =\< 28 days prior to registration or limited field radiation therapy \< 14 days prior to registration
• Full field radiation encompasses the entire area of known disease involvement and surrounding uninvolved but at-risk areas, e.g. subtotal nodal (mantle and upper abdomen) or total nodal irradiation
• Limited field radiation is restricted to treating only the known areas of clinical disease, e.g. involved-field therapy for lymphoma
• Major surgery (i.e., laparotomy) =\< 4 weeks prior to registration; minor surgery =\< 2 weeks prior to registration; Note: insertion of a vascular access device is not considered major or minor surgery in this regard
• Unresolved toxicities from prior therapy with the exception of alopecia that have not resolved to =\< grade 1, unless the patient has a chronic, stable =\< grade 2 toxicity that would not interfere with the evaluation of the study agents
• New York Heart Association classification III or IV
• Central nervous system (CNS) metastases or seizure disorder; Note: CNS metastases are allowed if previously treated and stable for at least 4 weeks

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Cilengitide; Paclitaxel; Taxes

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Julian Molina

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 12, 2011
• First Posted: January 13, 2011
• Study Start: December 1, 2010
• Primary Completion: March 1, 2015
• Last Updated: March 15, 2016

Record last verified: 2015-03

Locations

US (3)