Vitamin Supplementation in NSCLC Patients on Pemetrexed Based Chemotherapy

NCT02679443 | Completed

• 1 other identifier: NK/2376/DM/913
• Study Type: interventional
• Target: 161
• Locations: 1 country
• Sites: 1

Brief Summary

Folic acid (FA; folate) in the dose of 350-1,000 μg daily should be supplemented, daily, starting 7 days before the first dose of pemetrexed based chemotherapy and should be continued while the patient is on therapy and for 21 days after cessation of therapy. Vitamin B12 injections (1,000 μg i.m.) should also be started 1 week before the first dose of chemotherapy. However, the evidence for delaying chemotherapy by seven days for the purpose of giving vitamin B12 and FA supplementation is not robust. Observational and prospective single arm studies have not shown any increased toxicity if pemetrexed was started earlier than the recommended duration of supplementation. In a resource constrained setting, this will lead to one additional visit and 1-week chemotherapy delay which may be inconvenient for patients. Hence an open label, randomized control trial is being undertaken to evaluate if there are any differences in pemetrexed related hematological toxicity amongst patients who receive delayed initiation of chemotherapy (following 5 - 7 days of vitamin B12 and FA supplementation; Delayed Arm) as compared to those in whom vitamin B12 and FA supplementation is starting simultaneously (within 24 hours) of initiation of chemotherapy (Immediate Arm).

Conditions

Lung Adenocarcinoma; Neutropenia; Anemia; Thrombocytopenia; Nonsquamous Nonsmall Cell Neoplasm of Lung

Keywords

Lung Adenocarcinoma; Non-squamous NSCLC; Chemotherapy; Pemetrexed; Vitamin B12; Folate; Supplementation; Cytopenia

Outcome Measures

Primary Outcomes (1)

• Incidence of any grade hematological toxicity

  Incidence of Grade 1-5 Anemia, Grade 1-5 Neutropenia, Grade 1-5 Thrombocytopenia (all graded according to NCI CTCAE Version 3.0) related to pemetrexed-platinum doublet chemotherapy during the study period

  Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy

Secondary Outcomes (6)

• Incidence of grade 3/4 hematological toxicity

  Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy

• Number of doses of G-CSF administered

  Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy

• Number of doses of ESAs administered

  Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy

• Number of PRBC transfusions administered

  Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy

• Relative Dose Intensity (RDI) delivered

  Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy

Other Outcomes (1)

• Changes in serum levels of folic acid and homocysteine

  Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy

Study Arms (2)

Delayed Arm

NO INTERVENTION

Participants are started on folate and vitamin B12 supplementation for 5-7 days prior to initiation of chemotherapy

Immediate Arm

EXPERIMENTAL

Participants are started on folate and vitamin B12 supplementation simultaneously with chemotherapy (within 24 hours of initiation of chemotherapy)

Dietary Supplement: Folate and B12

Interventions

Folate and B12 DIETARY_SUPPLEMENT

Vitamin (folate and B12) supplementation started simultaneously with initiation of chemotherapy (within 24 hours of initiation of chemotherapy). The only difference from the delayed (no-intervention) arm is the timing of initiation of vitamin supplementation. Dose and mode of administration of vitamin B12 and folate supplementation remain similar in both arms.

Immediate Arm

Eligibility Criteria

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

You may qualify if:

• Locally advanced or metastatic (Stage IIIB/IV) NSCLC and Stage III A NSCLC, not scheduled for upfront surgical resection
• Nonsquamous histology (including adenocarcinoma)
• At least one unidimensionally measurable lesion, according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.0), or at least one nonmeasurable lesion that was assessable using conventional techniques or a spiral computed tomography scan
• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• No previous chemotherapy for advanced disease and no previous targeted molecular therapy
• Adequate liver and renal function;
• Previous radiation therapy is permitted if completed \>4 weeks before enrollment and the patient has recovered from any treatment-related toxicity.

You may not qualify if:

• Hemoglobin value \< 9gm/dl
• Required erythropoiesis stimulating agents or blood transfusions in the recent past (4 months)
• Symptomatic untreated brain metastasis
• Any previous malignancy
• Concurrent use of any other tumor therapy
• Active infection or a serious concomitant disorder
• Inability to interrupt nonsteroidal anti-inflammatory agents
• Inability or unwillingness to take folic acid, vitamin B12, or dexamethasone supplementation
• Pregnancy or breast feeding

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead

Study Sites (1)

PGIMER

Chandigarh, 160012, India

Location

Related Publications (2)

• Singh N, Baldi M, Kaur J, Muthu V, Prasad KT, Behera D, Bal A, Gupta N, Kapoor R. Timing of folic acid/vitamin B12 supplementation and hematologic toxicity during first-line treatment of patients with nonsquamous non-small cell lung cancer using pemetrexed-based chemotherapy: The PEMVITASTART randomized trial. Cancer. 2019 Jul 1;125(13):2203-2212. doi: 10.1002/cncr.32028. Epub 2019 Mar 2.

  PMID: 30825389 DERIVED

• Baldi M, Behera D, Kaur J, Kapoor R, Singh N. Rationale and Design of PEMVITASTART-An Open-label Randomized Trial Comparing Simultaneous Versus Standard Initiation of Vitamin B12 and Folate Supplementation in Nonsquamous, Non-Small-cell Lung Cancer Patients Undergoing First-line Pemetrexed-based Chemotherapy. Clin Lung Cancer. 2017 Jul;18(4):432-435. doi: 10.1016/j.cllc.2016.11.017. Epub 2016 Dec 2.

  PMID: 28073680 DERIVED

MeSH Terms

Conditions

Adenocarcinoma of Lung; Neutropenia; Anemia; Thrombocytopenia; Cytopenia

Interventions

Folic Acid; Vitamin B 12

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Agranulocytosis; Leukopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Blood Platelet Disorders

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds, 4 or More Rings; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Navneet Singh, MD DM

  PGIMER, Chandigarh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 1, 2016
• First Posted: February 10, 2016
• Study Start: July 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 25, 2017

Record last verified: 2017-04

Locations

IN (1)