Pemetrexed Disodium and Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer or Other Solid Tumors

NCT00387322 | Completed Phase 1 DMC

• 4 other identifiers: CDR0000505895P30CA093373UCDCC-159200412741
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Pemetrexed disodium and erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pemetrexed disodium together with erlotinib may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of two different schedules of pemetrexed disodium and erlotinib and to see how well they work in treating patients with advanced non-small cell lung cancer or other solid tumors.

Conditions

Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific; recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer

Outcome Measures

Primary Outcomes (2)

• Safety and feasibility (Phase I)

  October 2007

• Response rate (Phase II)

  Phase II not performed

Secondary Outcomes (6)

• Toxicity (Phase I)

  October 2007

• Maximum tolerated dose (Phase I)

  October 2007

• Preliminary efficacy (Phase I)

  October 2007

• Overall survival (Phase II)

  Phase II not performed

• Progression-free survival (Phase II)

  Phase II not performed

Study Arms (2)

Group 1

EXPERIMENTAL

Patients receive oral erlotinib hydrochloride once on days 2, 9, and 16 and pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of unacceptable toxicity or disease progression

Drug: erlotinib hydrochloride; Drug: pemetrexed disodium

Group 2

EXPERIMENTAL

Patients receive oral erlotinib hydrochloride once daily on days 2-16 and pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of unacceptable toxicity or disease progression.

Drug: erlotinib hydrochloride; Drug: pemetrexed disodium

Interventions

erlotinib hydrochloride DRUG

Given orally

Also known as: Tarceva

Group 1; Group 2

pemetrexed disodium DRUG

Given IV

Also known as: Alimta

Group 1; Group 2

Eligibility Criteria

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

You may qualify if:

• For the phase I portion of the study patients must have cytologically or histologically proven advanced solid tumors for which there is no standard effective therapy available. For the phase II portion patients must have cytologically or histologically proven selected stage IIIB (pleural effusion) or IV NSCLC. Patients with NSCLC that have progressed or recurred after first-line therapy for stage IIIA or IIIB may also be considered.
• For the phase II portion patients must have disease that has progressed or recurred after treatment with platinum-based therapy.
• Any number of prior chemotherapy regimens are allowed for the phase I portion and no more than 1 previous treatment for advanced NSCLC is allowed for the phase II portion.
• Patients must have measurable disease by RECIST criteria. Disease in previously irradiated sites is considered measurable if there is clear disease progression following radiation therapy. Patients with evaluable disease (bone metastases, pleural fluid, ascites, etc.) may be included in the phase I portion of the trial.
• Patients must be 18 years of age or older.
• Patients must have a performance status of 0-2 for phase I portion of study and a performance status of 0 -1 for the phase II portion of the trial.
• Patients must have an estimated survival of at least 3 months.
• Any prior chemotherapy that patients have received has to have been completed at least 4 weeks prior to start of treatment. For prior mitomycin chemotherapy a 6-week interval is required. Prior radiation must have been completed at least 2 weeks prior to start of therapy. Patients must have recovered from acute reversible side effects of prior chemotherapy regimens or radiotherapy to NCI-CTC \< grade 1 (excluding alopecia).
• Patients must have adequate renal function as documented by a serum creatinine \< 1.5 mg/dl or a calculated creatinine clearance of \> 45 ml/min (see appendix for formula for calculating creatinine clearance).
• Patients must have adequate liver function as documented by serum bilirubin \< 1.5 x ULN. AST must be \< 2.5 x institutional upper limit of normal.
• Patients must have a pretreatment granulocyte count of \>1500/mm3 and platelet count of \>100 000/mm3.
• Patients with asymptomatic treated brain metastasis (surgical resection or radiotherapy) may be included if they are neurologically stable and have been off steroids and anticonvulsants for at least 4 weeks. Because of the possibility of treatment related neurological toxicity it is difficult to evaluate for toxicity in the presence of symptomatic brain metastasis.
• All patients must give voluntary written informed consent.
• Patients must be able to take and retain oral medication.
• Patients of reproductive potential must agree to use effective contraceptive method while on treatment and for 3 months afterwards as the effects of these drugs on the unborn fetus are unknown.

You may not qualify if:

• Patients may not have previously received Pemetrexed or an EGFR-directed therapy.
• Females can not be pregnant or breastfeeding as the effects of these drugs on the unborn fetus are unknown. Documentation of a negative serum pregnancy test is required for all women of reproductive potential.
• Patients with symptomatic brain metastasis or still requiring steroids and anti-convulsants may not be included.
• No other prior malignancy is allowed for the phase II portion except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for over five years.
• Patients cannot take non-steroidal anti-inflammatory agents (NSAIDS) or salicylates 2 days prior and 2 days following (5 days pre and post for long-acting NSAIDS) administration of pemetrexed due to concerns of increased risk of renal toxicity.
• Patients with clinically significant ophthalmologic abnormalities will be excluded. This includes severe dry eye syndrome, keratoconjunctivitis sicca, Sjogren's syndrome, severe exposure keratopathy, or other disorders that might increase the risk of corneal epithelial injury.

Sponsors & Collaborators

• University of California, Davis: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California Davis Cancer Center

Sacramento, California, 95817, United States

Location

Related Publications (1)

• Davies AM, Ho C, Beckett L, Lau D, Scudder SA, Lara PN, Perkins N, Gandara DR. Intermittent erlotinib in combination with pemetrexed: phase I schedules designed to achieve pharmacodynamic separation. J Thorac Oncol. 2009 Jul;4(7):862-8. doi: 10.1097/JTO.0b013e3181a94b08.

  PMID: 19494788 RESULT

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride; Pemetrexed

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• David Gandara, MD

  University of California, Davis

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 12, 2006
• First Posted: October 13, 2006
• Study Start: March 1, 2005
• Primary Completion: October 1, 2007
• Study Completion: May 1, 2009
• Last Updated: March 29, 2010

Record last verified: 2010-03

Locations

US (1)