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Phase I/II Study of Two Different Schedules of Pemetrexed (ALIMTA) and Erlotinib (TARCEVA) in Advanced Solid Tumors, With Emphasis on Non-Small Cell Lung Cancer (NSCLC)


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Lung Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase I/II Study of Two Different Schedules of Pemetrexed (ALIMTA) and Erlotinib (TARCEVA) in Advanced Solid Tumors, With Emphasis on Non-Small Cell Lung Cancer (NSCLC)


OBJECTIVES:

Primary

- Determine the safety and feasibility of combining pemetrexed disodium with erlotinib
hydrochloride in patients with advanced non-small lung cancer (NSCLC) or other solid
tumors. (Phase I)

- Determine the response rate in patients with NSCLC treated with pemetrexed disodium in
combination with erlotinib hydrochloride. (Phase II)

Secondary

- Compare toxicity differences between different schedules of pemetrexed disodium and
erlotinib hydrochloride. (Phase I)

- Determine the maximum tolerated dose (MTD) of 2 different schedules of pemetrexed
disodium and erlotinib hydrochloride. (Phase I)

- Determine, preliminarily, the efficacy of the combination of pemetrexed disodium and
erlotinib hydrochloride in patients with advanced solid tumors. (Phase I)

- Assess the overall survival and progression-free survival. (Phase II)

- Determine the frequency and severity of toxicities associated with the administration
of pemetrexed disodium and erlotinib hydrochloride. (Phase II)

OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II
open-label study.

- Phase I: Patients are assigned to 1 of 2 treatment groups in an alternating fashion.
Once accrual to the first dose level in group 1 is complete, group 2 will open for
accrual to its first dose level.

- Group 1: 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.

- Group 2: 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.

In both groups, patients may continue to receive erlotinib hydrochloride alone after
completion of 6 courses of erlotinib hydrochloride in combination with pemetrexed disodium.

In both groups, cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride
and pemetrexed disodium until the maximum tolerated dose (MTD) is determined. The MTD is
defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience
dose-limiting toxicity.

- Phase II: Patients receive pemetrexed disodium at the MTD and erlotinib hydrochloride
at the MTD as in group 1 or 2 (whichever is more favorable).

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 92 patients will be accrued for this study.


Inclusion Criteria:



- 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.

- Patients on coumadin should have their INR monitored at least once per week or more
frequently depending on the investigators judgement. There have been some case
reports of increased INR when coumadin is co-administered with OSI-774/placebo.

Exclusion Criteria:

- 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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and feasibility (Phase I)

Outcome Time Frame:

October 2007

Safety Issue:

Yes

Principal Investigator

David Gandara, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, Davis

Authority:

United States: Federal Government

Study ID:

CDR0000505895

NCT ID:

NCT00387322

Start Date:

March 2005

Completion Date:

May 2009

Related Keywords:

  • Lung Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • 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
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Neoplasms

Name

Location

University of California Davis Cancer CenterSacramento, California  95817