Clinical trial NCT00006036: Liposomal Lurtotecan Plus Cisplatin in Treating Patients With Advanced or Metastatic Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Head and Neck Cancer
Lung Cancer
Ovarian Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: 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
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2004-03-25
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of liposomal lurtotecan plus cisplatin in treating patients who have advanced or metastatic solid tumors.

Detailed description: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Hamilton
country: Canada
facility: Cancer Care Ontario-Hamilton Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: Margaret and Charles Juravinski Cancer Centre
name: Hal W. Hirte, MD, FRCP(C)
role: STUDY_CHAIR
References:
citation: MacKenzie MJ, Hirte HW, Siu LL, Gelmon K, Ptaszynski M, Fisher B, Eisenhauer E. A phase I study of OSI-211 and cisplatin as intravenous infusions given on days 1, 2 and 3 every 3 weeks in patients with solid cancers. Ann Oncol. 2004 Apr;15(4):665-70. doi: 10.1093/annonc/mdh133.