A Phase I Study of NX 211 in Combination With Cisplatin Given as an IV Infusion Days 1, 2, and 3 Every 3 Weeks in Patients With Solid Tumors
18 Years
N/A
Both
Head and Neck Cancer, Lung Cancer, Ovarian Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Study of NX 211 in Combination With Cisplatin Given as an IV Infusion Days 1, 2, and 3 Every 3 Weeks in Patients With Solid Tumors
OBJECTIVES: I. Determine the maximum tolerated dose and recommended phase II dose of
lurtotecan liposome and cisplatin in patients with advanced solid tumors. II. Determine the
toxicity profile, dose-limiting toxic effects, and the pharmacokinetics of this treatment
regimen in this patient population. III. Determine any correlation between toxicity profile
and pharmacokinetics of this treatment regimen in these patients. IV. Determine the
objective tumor response to this treatment regimen in patients with measurable disease
(previously untreated solid tumors) entered at the recommended phase II dose.
OUTLINE: This is an open-label, multicenter, dose-escalation study of lurtotecan liposome.
Patients receive cisplatin IV over 1 hour followed by lurtotecan liposome IV over 30 minutes
on days 1-3. Treatment repeats every 3 weeks in the absence of disease progression or
unacceptable toxicity. Once the total dose of cisplatin is reached, patients receive
lurtotecan liposome alone. Patients achieving complete response (CR) continue therapy for 2
courses after documentation of confirmed CR. Patients achieving partial response (PR)
continue therapy until progression or for 2 courses after documentation of stable PR.
Patients with stable disease continue therapy for a maximum of 6 courses. Cohorts of 3-6
patients receive escalating doses of lurtotecan liposome until the maximum tolerated dose
(MTD) is reached. The MTD is defined as the dose at which at least 2 of 6 patients
experience dose-limiting toxicity. Once the MTD is determined, up to 10 patients with
previously untreated solid tumors are treated at the recommended phase II dose (1 dose below
the MTD). Patients are followed at 4 weeks and then every 3 months for 1 year.
PROJECTED ACCRUAL: A total of 20-25 patients will be accrued for this study within 12-15
months.
Inclusion Criteria
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed advanced and/or
metastatic solid tumor refractory to standard curative therapy or for which no curative
therapy exists Clinically or radiographically documented disease No tumor marker elevation
as only evidence of disease No untreated brain or meningeal metastases Previously treated
and stable CNS metastases allowed (i.e., no evidence of increasing disease by CT scan for
at least 4 weeks) Recommended phase II dose portion of study: Previously untreated
advanced and/or metastatic disease for which a cisplatin-based regimen is indicated (e.g.,
non-small cell lung cancer, small cell lung cancer, ovarian, or head and neck cancer) At
least one measurable lesion at least 20 mm by physical exam or x-ray or at least 10 mm by
spiral CT scan
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy:
Not specified Hematopoietic: Absolute granulocyte count at least 1,500/mm3 Platelet count
at least 100,000/mm3 Hepatic: Bilirubin no greater than upper limit of normal (ULN)
AST/ALT no greater than 2.5 times ULN (5 times ULN if documented liver metastases) Renal:
Creatinine no greater than ULN OR Creatinine clearance at least 60 mL/min Other: No
greater than grade 1 neuropathy or ototoxicity No other prior or concurrent malignancy
within the past 5 years except curatively treated basal or squamous cell skin cancer or
cervical cancer (for recommended phase II dose) No active or uncontrolled infections No
other serious illnesses or medical conditions that would preclude study No known
hypersensitivity to systemic liposomal formulation or any drug chemically related to study
drug Not pregnant or nursing Negative pregnancy test Fertile patients must use effective
contraception
PRIOR CONCURRENT THERAPY: Biologic therapy: See Chemotherapy Recovered from prior
immunotherapy Chemotherapy: See Disease Characteristics No more than 1 prior chemotherapy
regimen (adjuvant and/or metastatic) except for nonmyelosuppressive agents (e.g., signal
transduction inhibitors or immunotherapy) At least 3 weeks since prior chemotherapy (6
weeks for nitrosoureas and mitomycin and 4 weeks for carboplatin) and recovered At least 1
year since prior high-dose chemotherapy with marrow or stem cell support No prior total
cisplatin dose of more than 300 mg/m2 No prior chemotherapy (for recommended phase II
dose) Endocrine therapy: Prior hormonal therapy allowed Radiotherapy: At least 4 weeks
since prior radiotherapy and recovered No prior radiotherapy to more than 25% of bone
marrow reserve, except for low-dose nonmyelosuppression Surgery: Not specified Other: At
least 4 weeks since other prior experimental drugs or anticancer therapy and recovered No
other concurrent investigational or anticancer therapy
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Hal W. Hirte, MD, FRCP(C)
Investigator Role:
Study Chair
Investigator Affiliation:
Margaret and Charles Juravinski Cancer Centre
Authority:
United States: Federal Government
Study ID:
I133
NCT ID:
NCT00006036
Start Date:
April 2000
Completion Date:
December 2009
Related Keywords:
- Head and Neck Cancer
- Lung Cancer
- Ovarian Cancer
- Unspecified Adult Solid Tumor, Protocol Specific
- recurrent non-small cell lung cancer
- stage III ovarian epithelial cancer
- stage IV ovarian epithelial cancer
- recurrent ovarian epithelial cancer
- extensive stage small cell lung cancer
- recurrent small cell lung cancer
- stage IV nasopharyngeal cancer
- stage IIIA non-small cell lung cancer
- stage IIIB non-small cell lung cancer
- stage IV non-small cell lung cancer
- unspecified adult solid tumor, protocol specific
- untreated metastatic squamous neck cancer with occult primary
- recurrent metastatic squamous neck cancer with occult primary
- ovarian stromal cancer
- stage III ovarian germ cell tumor
- stage IV ovarian germ cell tumor
- recurrent ovarian germ cell tumor
- stage III squamous cell carcinoma of the lip and oral cavity
- stage III basal cell carcinoma of the lip
- stage III verrucous carcinoma of the oral cavity
- stage III mucoepidermoid carcinoma of the oral cavity
- stage III adenoid cystic carcinoma of the oral cavity
- stage IV squamous cell carcinoma of the lip and oral cavity
- stage IV basal cell carcinoma of the lip
- stage IV verrucous carcinoma of the oral cavity
- stage IV mucoepidermoid carcinoma of the oral cavity
- stage IV adenoid cystic carcinoma of the oral cavity
- recurrent squamous cell carcinoma of the lip and oral cavity
- recurrent basal cell carcinoma of the lip
- recurrent verrucous carcinoma of the oral cavity
- recurrent mucoepidermoid carcinoma of the oral cavity
- recurrent adenoid cystic carcinoma of the oral cavity
- stage III squamous cell carcinoma of the oropharynx
- stage III lymphoepithelioma of the oropharynx
- stage IV squamous cell carcinoma of the oropharynx
- stage IV lymphoepithelioma of the oropharynx
- recurrent squamous cell carcinoma of the oropharynx
- recurrent lymphoepithelioma of the oropharynx
- stage III squamous cell carcinoma of the nasopharynx
- stage III lymphoepithelioma of the nasopharynx
- stage IV squamous cell carcinoma of the nasopharynx
- stage IV lymphoepithelioma of the nasopharynx
- recurrent squamous cell carcinoma of the nasopharynx
- recurrent lymphoepithelioma of the nasopharynx
- stage III squamous cell carcinoma of the hypopharynx
- stage IV squamous cell carcinoma of the hypopharynx
- recurrent squamous cell carcinoma of the hypopharynx
- stage III squamous cell carcinoma of the larynx
- stage III verrucous carcinoma of the larynx
- stage IV squamous cell carcinoma of the larynx
- stage IV verrucous carcinoma of the larynx
- recurrent squamous cell carcinoma of the larynx
- recurrent verrucous carcinoma of the larynx
- stage III squamous cell carcinoma of the paranasal sinus and nasal cavity
- stage III inverted papilloma of the paranasal sinus and nasal cavity
- stage III midline lethal granuloma of the paranasal sinus and nasal cavity
- stage III esthesioneuroblastoma of the paranasal sinus and nasal cavity
- stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
- stage IV inverted papilloma of the paranasal sinus and nasal cavity
- stage IV midline lethal granuloma of the paranasal sinus and nasal cavity
- stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity
- recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
- recurrent inverted papilloma of the paranasal sinus and nasal cavity
- recurrent midline lethal granuloma of the paranasal sinus and nasal cavity
- recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity
- borderline ovarian surface epithelial-stromal tumor
- ovarian sarcoma
- Head and Neck Neoplasms
- Lung Neoplasms
- Ovarian Neoplasms
- Neoplasms
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