Study of Pemetrexed Plus Cisplatin as First-line Therapy in Patients With Advanced Non-squamous NSCLC

Study of Pemetrexed Disodium Plus Cisplatin as First-line Therapy in Patients With Advanced Non-squamous Cell Lung Cancer: a Phase IIA Pharmacogenomic Trial

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01088906

Acronym

Phalcis

Enrollment

Registered

2010-03-17

Start date

2010-01-31

Completion date

2014-04-30

Last updated

2024-10-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Carcinoma, Non Small Cell Lung

Keywords

Phalcis, BRCA1, RAP80, TS, First line, Non-squamous

Brief summary

This is a study of pemetrexed disodium plus cisplatin as first-line therapy in patients with advanced non-squamous cell lung cancer. This is a phase IIA pharmacogenomic trial.

Detailed description

This is a non-randomized, phase IIA pharmacogenomic, open label, uncontrolled, efficacy study in patients with advanced non-squamous cell lung cancer as a first line therapy.

Interventions

DRUGPemetrexed/Cisplatin

Pemetrexed 500 mg/m2 IV followed by cisplatin 75 mg/m2 IV every 21 days. A cycle is 21 day.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Histologic or cytologic diagnosis of non-squamous NSCLC, that is not amenable to curative treatment with surgery or radiation therapy. This population encompasses advanced stage patients with select stage IIIB (with pleural or pericardial effusion) or stage IV disease. Histologic or cytologic documentation of recurrence is required in patients who were previously completely resected and now have progressive disease. * Tissue must be available to generate and apply the genomics predictor. If not obtained at the time of diagnosis, then subject must consent to another biopsy. If patient had prior radiation therapy, tissue biopsy for genomics analysis must be outside radiation field. * At least one, non-radiated, measurable lesion by RECIST criteria. * ECOG performance status of 0 or 1 * No prior chemotherapy, biologic or targeted therapy for any malignancy. * Prior radiation therapy is permitted if ≥1 week since completion of radiation treatment. Radiation must be \<25% of bone marrow reserve. * Age greater than 18 years. * No previous or concomitant malignancy in the past 5 years other than surgical management for carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin. * No other serious medical or psychiatric illness. * Signed informed consent. * Females of child-bearing potential (not surgically sterilized and between menarche and 1 year post menopause) must test negative for pregnancy within 7 days prior to or at the time of enrollment based on a serum pregnancy test. Both sexually active males and females of reproductive potential must agree to use a reliable method of birth control, as determined by the patient and their health care team, during the study and for 3 months following the last dose of study drug. * Required laboratory data within two weeks of enrollment: 1. ANC or AGC greater than 1500 per uL 2. Platelets greater than 100,000 per uL 3. Total bilirubin less than 1.5mg/dL 4. Creatinine clearance greater than or equal to 45 ml/min. 5. SGOT/SGPT less than or equal to 3x/ULN except in presence of known hepatic metastases in which it may be up to 5x ULN.

Exclusion criteria

* Patients with squamous cell NSCLC. * Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. * Concurrent administration of any other anti-tumor therapy. * Inability to comply with protocol or study procedures. * Active infection requiring IV antibiotics, antifungal or antiviral agents, that in the opinion of the investigator would compromise the patient's ability to tolerate therapy. * Documented symptomatic or untreated central nervous system (CNS) metastases (except if adequately treated and stable for at least 2 weeks). * Major surgery within 2 weeks of study or other serious concomitant systemic disorders that, in the opinion or the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study. * Myocardial infarction having occurred less than 6 months before inclusion, any known uncontrolled arrhythmia, symptomatic angina pectoris, active ischemia or cardiac failure not controlled by medications. * Have peripheral neuropathy of CTCAE Grade 1 or higher * Contraindications to corticosteroids. * Inability or unwillingness to take folic acid or vitamin B12 supplementation. * Unwillingness to stop taking herbal supplements while on study. * Presence of clinically significant third-space fluid collections (for example, ascites or pleural effusions) that cannot be controlled by drainage or other procedures prior to study entry and throughout study enrollment as the distribution of pemetrexed in this fluid space is not fully understood. * Recent (within 30 days before enrollment) or concurrent yellow fever vaccination. * Have prior known allergic/hypersensitivity reaction to any of the components of study treatment * Inability to discontinue administration of aspirin at a dose greater than 1300 mg/day or other non-steroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days for long-acting agents such as piroxicam). * Female patients that is pregnant or breast-feeding.

Design outcomes

Primary

Measure	Time frame	Description
Objective Response Rate	From start of treatment to end of follow up, up to 24 months	The percentage of patients who have experienced a tumor response since the start of treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Secondary

Measure	Time frame	Description
Time to Progression	From the date of enrollment until end of follow up, up to 24 months.	This interval is measured in months from the date of entry into the study until the first date of the appearance of new metastatic lesions or objective progression of the disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time to Progression of Patients According the Results of Biomarker BRCA1	From the date of enrollment until end of follow up, up to 24 months.	This interval is measured from the date of entry into the study until the first date of the appearance of new metastatic lesions or objective progression of the disease for patients with biomarker BRCA1.
Time to Progression of Patients According the Results of Biomarker RAP80	From the date of enrollment until end of follow up, up to 24 months.	This interval is measured from the date of entry into the study until the first date of the appearance of new metastatic lesions or objective progression of the disease.
Overall Survival	From the date of enrollment until end of follow up, up to 24 months.	Overall survival is measured from the date of enrollment to the date of death from any cause
Overall Survival of Patients According the Results of Biomarker BRCA1	From the date of enrollment until end of follow up, up to 24 months.	Overall survival is measured from the date of enrollment to the date of death from any cause
Overall Survival of Patients According the Results of Biomarker RAP80	From the date of enrollment until end of follow up, up to 24 months.	Overall survival is measured from the date of enrollment to the date of death from any cause
Overall Survival of Patients According the Results of Biomarker TS	From the date of enrollment until end of follow up, up to 24 months.	Overall survival is measured from the date of enrollment to the date of death from any cause.
Time to Progression of Patients According the Results of Biomarker TS	From the date of enrollment until end of follow up, up to 24 months.	This interval is measured from the date of entry into the study until the first date of the appearance of new metastatic lesions or objective progression of the disease.

Countries

Spain

Participant flow

Recruitment details

Dates of recruitment: start date: 20 January 2010 and ended at 19 February 2014.

Participants by arm

Arm	Count
EXPERIMENTAL ARM Pemetrexed 500 mg/m2 IV + cisplatin 75 mg/m2 every 21 days Pemetrexed/Cisplatin: Pemetrexed 500 mg/m2 IV followed by cisplatin 75 mg/m2 IV every 21 days. A cycle is 21 day. Total: 6 cycles.	52
Total	52

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Did not receive study treatment	3
Overall Study	Inclusion error	1
Overall Study	Missing data	1

Baseline characteristics

Characteristic	EXPERIMENTAL ARM
Age, Continuous	62 years
ECOG ECOG 0	14 participants
ECOG ECOG 1	33 participants
ECOG ECOG UK	5 participants
Histology Adenocarcinoma	51 participants
Histology Large Cell Lung Carcinoma	1 participants
Region of Enrollment Spain	52 participants
Sex: Female, Male Female	13 Participants
Sex: Female, Male Male	39 Participants
Smoking status Former	31 participants
Smoking status Never	5 participants
Smoking status Smoker	16 participants
Treatment compliance Cycle 1 completed	1 participants
Treatment compliance Cycle 2 completed	7 participants
Treatment compliance Cycle 3 completed	6 participants
Treatment compliance Cycle 4 completed	8 participants
Treatment compliance Cycle 5 completed	4 participants
Treatment compliance Cycle 6 completed	26 participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	9 / 52
other Total, other adverse events	40 / 52
serious Total, serious adverse events	25 / 52

Outcome results

Primary

Objective Response Rate

The percentage of patients who have experienced a tumor response since the start of treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Time frame: From start of treatment to end of follow up, up to 24 months

Population: The percentage of patients who have experienced tumor regression since the start of treatment (Complete response + Partial response) among the total of patients ORR = 26%

Arm	Measure	Group	Value (NUMBER)
EXPERIMENTAL ARM	Objective Response Rate	Stable disease	44 percentage of participants
EXPERIMENTAL ARM	Objective Response Rate	Partial response	22 percentage of participants
EXPERIMENTAL ARM	Objective Response Rate	Complete response	4 percentage of participants
EXPERIMENTAL ARM	Objective Response Rate	Progression	30 percentage of participants

p-value: 0.05Regression, Logistic

Secondary