Trial Outcomes & Findings for Study of Pralatrexate vs. Erlotinib for Non-Small Cell Lung Cancer After at Least 1 Prior Platinum-based Treatment (NCT NCT00606502)

Last Updated: 2021-03-05

Results Overview

OS was defined as the length of time from randomization until death due to any cause. Patients who were alive at the time of the data cut-off date were censored at the last contact date.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

201 participants

Primary outcome timeframe

Assessed from date of randomization no less frequently than every 16 weeks for up to 2 years after randomization.

Results posted on

2021-03-05

Participant Flow

Patients were enrolled between January 2008 and June 2009 across 43 study sites in 6 countries.

Participant milestones

Participant milestones
Measure	Pralatrexate 190 or 230 mg/m2 starting dose with increases or decreases to 150 to 270 mg/m2 per protocol, administered as an IV push over 3-5 minutes on days 1 and 15 of a 4-week cycle (ie, every 2 weeks)	Erlotinib 150 mg tablet taken orally daily
Randomization STARTED	100	101
Randomization COMPLETED	97	101
Randomization NOT COMPLETED	3	0
Treatment STARTED	97	101
Treatment COMPLETED	97	98
Treatment NOT COMPLETED	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Pralatrexate 190 or 230 mg/m2 starting dose with increases or decreases to 150 to 270 mg/m2 per protocol, administered as an IV push over 3-5 minutes on days 1 and 15 of a 4-week cycle (ie, every 2 weeks)	Erlotinib 150 mg tablet taken orally daily
Randomization Randomized but not treated	3	0
Treatment Treatment ongoing at time of data cutoff	0	3

Baseline Characteristics

Study of Pralatrexate vs. Erlotinib for Non-Small Cell Lung Cancer After at Least 1 Prior Platinum-based Treatment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pralatrexate n=100 Participants	Erlotinib n=101 Participants	Total n=201 Participants Total of all reporting groups
Age, Customized Between 18 and 65 years	58 participants n=5 Participants	60 participants n=7 Participants	118 participants n=5 Participants
Age, Customized >=65 years	42 participants n=5 Participants	41 participants n=7 Participants	83 participants n=5 Participants
Age, Continuous	63.0 years STANDARD_DEVIATION 9.0 • n=5 Participants	62.0 years STANDARD_DEVIATION 9.1 • n=7 Participants	63.0 years STANDARD_DEVIATION 9.0 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	33 Participants n=7 Participants	64 Participants n=5 Participants
Sex: Female, Male Male	69 Participants n=5 Participants	68 Participants n=7 Participants	137 Participants n=5 Participants
Region of Enrollment United States	31 participants n=5 Participants	37 participants n=7 Participants	68 participants n=5 Participants
Region of Enrollment Czech Republic	17 participants n=5 Participants	20 participants n=7 Participants	37 participants n=5 Participants
Region of Enrollment Hungary	17 participants n=5 Participants	15 participants n=7 Participants	32 participants n=5 Participants
Region of Enrollment India	11 participants n=5 Participants	12 participants n=7 Participants	23 participants n=5 Participants
Region of Enrollment Brazil	13 participants n=5 Participants	9 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Argentina	11 participants n=5 Participants	8 participants n=7 Participants	19 participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed from date of randomization no less frequently than every 16 weeks for up to 2 years after randomization.

OS was defined as the length of time from randomization until death due to any cause. Patients who were alive at the time of the data cut-off date were censored at the last contact date.

Outcome measures

Outcome measures
Measure	Pralatrexate n=100 Participants	Erlotinib n=101 Participants
Overall Survival (OS) of Patients Receiving Pralatrexate vs. Erlotinib	6.7 Months Survival Interval 5.3 to 9.0	7.0 Months Survival Interval 3.9 to 7.9

SECONDARY outcome

Timeframe: Assessed every 8 weeks for the first 24 weeks, then every 16 weeks for up to 2 years or until PD or start of subsequent treatment.

Population: Based on all treated patients with measurable disease at baseline. Patients who were declared unevaluable for response were considered nonresponders and were included in the calculation of response rate. Patients were unevaluable if they were off-treatment prior to first response assessment, never received treatment or had unconfirmed responses.

Number of patients whose tumors responded to Pralatrexate or Erlotinib, using the Response Criteria in Solid Tumors (RECIST).

Outcome measures

Outcome measures
Measure	Pralatrexate n=97 Participants	Erlotinib n=98 Participants
Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib Complete + Partial Response	2 Participants	7 Participants
Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib Complete Response (CR)	0 Participants	1 Participants
Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib Partial Response (PR)	2 Participants	6 Participants
Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib Stable Disease (SD)	33 Participants	35 Participants
Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib Progressive Disease (PD)	29 Participants	36 Participants
Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib Disease Control (CR+PR+SD)	35 Participants	42 Participants
Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib Unable to Evaluate	2 Participants	0 Participants
Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib Missing (off or no treatment, not confirmed)	31 Participants	20 Participants

SECONDARY outcome

Timeframe: Assessed every 8 weeks for the first 24 weeks, then every 16 weeks for up to 2 years or until PD or start of subsequent treatment.

Population: Patients who were alive without a disease response assessment of PD as of the data cut-off date were censored at the last disease assessment date or the date of randomization, whichever was later. Patients with no response assessments after baseline were censored at date of randomization resulting in a duration of PFS of 1 day.

PFS was calculated as the number of days from randomization to the date of radiological evidence of PD or death due to any cause.

Outcome measures

Outcome measures
Measure	Pralatrexate n=100 Participants	Erlotinib n=101 Participants
Progression-free Survival (PFS) of Patients Receiving Pralatrexate vs. Erlotinib	3.4 months Interval 2.1 to 4.7	2.8 months Interval 2.1 to 3.7

SECONDARY outcome

Timeframe: Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal).

Population: Adverse Events (AEs) and Serious AEs (SAEs) are presented regardless of causality for patients who received at least one dose of Pralatrexate or Erlotinib. Events were graded by the investigator using the NCI CTCAE Scale (version 3.0) which provides a grading scale for each AE term. Grade 3 = Severe Grade 4 = Life-threatening or disabling

Outcome measures

Outcome measures
Measure	Pralatrexate n=97 Participants	Erlotinib n=101 Participants
Adverse Events of Patients Receiving Pralatrexate vs. Erlotinib At least one AE	75 Treated Participants	77 Treated Participants
Adverse Events of Patients Receiving Pralatrexate vs. Erlotinib Grade 3 AEs	25 Treated Participants	18 Treated Participants
Adverse Events of Patients Receiving Pralatrexate vs. Erlotinib Grade 4 AEs	5 Treated Participants	0 Treated Participants
Adverse Events of Patients Receiving Pralatrexate vs. Erlotinib At least one SAE	14 Treated Participants	2 Treated Participants

Adverse Events

Pralatrexate

Serious events: 31 serious events

Other events: 91 other events

Deaths: 0 deaths

Erlotinib

Serious events: 32 serious events

Other events: 94 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Monitor

Allos Therapeutics, Inc

Phone: 303-426-6262

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Allos agreements with investigators (PIs) may vary. The PI may publish/make public data from the study after the earlier of publication by Allos or 24 months after database lock. Allos is allowed 60 days to review and comment on the communication prior to public release. Allos can request removal of confidential information (other than study results).
Publication restrictions are in place

Restriction type: OTHER

Measure	Pralatrexate n=97 participants at risk	Erlotinib n=101 participants at risk
Gastrointestinal disorders stomatitis	63.9% 62/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	4.0% 4/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Gastrointestinal disorders diarrhoea	15.5% 15/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	31.7% 32/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Gastrointestinal disorders nausea	12.4% 12/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	16.8% 17/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Gastrointestinal disorders vomiting	10.3% 10/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	9.9% 10/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Gastrointestinal disorders constipation	3.1% 3/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	7.9% 8/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Skin and subcutaneous tissue disorders dermatitis acneiform	4.1% 4/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	27.7% 28/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Skin and subcutaneous tissue disorders rash maculo-papular	4.1% 4/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	20.8% 21/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Skin and subcutaneous tissue disorders dry skin	2.1% 2/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	8.9% 9/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
General disorders fatigue	25.8% 25/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	15.8% 16/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
General disorders asthenia	15.5% 15/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	7.9% 8/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
General disorders oedema peripheral	5.2% 5/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	6.9% 7/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Respiratory, thoracic and mediastinal disorders dyspnoea	12.4% 12/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	21.8% 22/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Respiratory, thoracic and mediastinal disorders cough	11.3% 11/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	16.8% 17/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Metabolism and nutrition disorders anorexia	16.5% 16/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	18.8% 19/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Metabolism and nutrition disorders hypokalaemia	5.2% 5/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	7.9% 8/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Musculoskeletal and connective tissue disorders back pain	3.1% 3/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	9.9% 10/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Musculoskeletal and connective tissue disorders musculoskeletal pain	4.1% 4/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	8.9% 9/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Blood and lymphatic system disorders anaemia	20.6% 20/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	11.9% 12/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Blood and lymphatic system disorders thrombocytopenia	12.4% 12/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	0.99% 1/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Infections and infestations bronchitis	5.2% 5/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	7.9% 8/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Investigations weight decreased	8.2% 8/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	9.9% 10/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.
Eye disorders conjunctivitis	6.2% 6/97 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.	5.0% 5/101 • Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal). Events reported for all patients who received at least one dose of Pralatrexate or Erlotinib.