Lung AdenocarcinomaPEMVITASTARTNCT02679443
Vitamin Supplementation in NSCLC Patients on Pemetrexed Based Chemotherapy
A study testing Folate and B12 in people with Lung Adenocarcinoma and Neutropenia, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Adenocarcinoma, Neutropenia, Anemia
- What is being tested?
- Folate and B12
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 161 participants
- Where
- 1 siteIndia
- Study dates
- Jul 2015to Dec 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- Inability to interrupt nonsteroidal anti-inflammatory agents
- Inability or unwillingness to take folic acid, vitamin B12, or dexamethasone supplementation
- Pregnancy or breast feeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Optimum Duration of Vitamin B12 and Folate Supplementation in Non-squamous Non-small Cell Lung Cancer (NSCLC) Patients Undergoing Pemetrexed Containing Chemotherapy: a Randomized Controlled Trial
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).
Read the detailed description
Chemotherapy Regimen:
All patients will receive pemetrexed and cisplatin in doses of 500 mg and 65 mg, respectively, per square meter of body surface area each on day 1 of a 3-week cycle. Patients with contraindications to administration of cisplatin, those who are intolerant to cisplatin, or develop grade 3 or 4 adverse events from cisplatin will be given carboplatin in combination with pemetrexed. Carboplatin will be given at a dose calculated to produce an area under the concentration-time curve (AUC) of 5.0mg/mL/min. Dose modifications of either pemetrexed or the platinum agent or both will be done in case of significant change in PS or toxicity from or intolerance to dose administered in the previous cycle.
Supplementation:
- Folic acid (FA) supplementation will be given to all patients orally in the dose of 5 ml (1000 μg) once daily of VITCOFOL (FDC Limited, Mumbai, India) pediatric formulation, which contains 200 μg FA/ml of the preparation. Patients will be instructed to measure the prescribed dose using a 5 ml plastic syringe containing markings at every 0.5 ml. Patients will also be instructed not to take any additional multivitamin supplements. In addition to FA supplementation, all patients will also be started simultaneously on oral iron (ferrous sulphate 200 mg twice a day). Once initiated, both FA and ferrous sulphate will be given on a daily basis and continued throughout the duration of chemotherapy and for at least 3 weeks beyond the last cycle.
- Vitamin B12 supplementation will be given to all patients intramuscularly in the dose of 1000 μg along with each cycle of chemotherapy (maximum of six doses during the study period).
- Conditions
- Lung Adenocarcinoma, Neutropenia, Anemia, Thrombocytopenia, Nonsquamous Nonsmall Cell Neoplasm of Lung
- Being tested
- Folate and B12
- Keywords
- Lung Adenocarcinoma, Non-squamous NSCLC, Chemotherapy, Pemetrexed, Vitamin B12, Folate, Supplementation, Cytopenia
- Medical subject headings
- Adenocarcinoma of Lung, Neutropenia, Anemia, Thrombocytopenia, Cytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Folate and B12Dietary 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.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Dietary Supplement: Folate and B12 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Incidence of Grade 3-4 Anemia, Grade 3-4 Neutropenia, Grade 3-4 Thrombocytopenia (all graded according to NCI CTCAE Version 3.0) related to pemetrexed-platinum doublet chemotherapy during the study period
Measured: 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
Number of doses of G-CSF (granulocyte colony stimulating factor) administered during the study period
Measured: Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy
Number of doses of ESAs administered
Number of doses of ESAs (erythropoiesis stimulating agents) administered during the study period
Measured: Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy
Number of PRBC transfusions administered
Number of PRBC (packed red blood cell) transfusions administered during the study period
Measured: Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy
Relative Dose Intensity (RDI) delivered
RDI (in percentage) will be calculated as [(delivered dosage/predicted dosage)*100]. This will be calculated separately for pemetrexed and platinum compounds for each chemotherapy cycle and also averaged for the total duration of chemotherapy
Measured: Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy
Number of Inter-Cycle Delays (ICDs)
ICD will be defined as a delay of at least 7 days between scheduled date and actual date of administration of a given cycle of chemotherapy
Measured: Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2016 (estimated)
- Study startJul 2015
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Lung AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 161 participants (actual)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Navneet Singh, Post Graduate Institute of Medical Education and Research, Chandigarh
- Investigators
- Navneet Singh, MD DM, Principal investigator, PGIMER, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02679443
- Sponsor's protocol ID
- NK/2376/DM/913
- Acronym
- PEMVITASTART
- Status last verified
- Apr 2017
- First submitted
- 1 Feb 2016
- Last updated
- 25 Apr 2017
- Results posted
- No
Publications
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.
PubMed 30825389Baldi 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.
PubMed 28073680
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimum Duration of Vitamin B12 and Folate Supplementation in Non-squamous Non-small Cell Lung Cancer (NSCLC) Patients Undergoing Pemetrexed Containing Chemotherapy: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT02679443
- Acronym / sponsor ID
- PEMVITASTART / NK/2376/DM/913
- 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 161 participants (actual)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- Jul 2015 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 10 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Chemotherapy Regimen:
All patients will receive pemetrexed and cisplatin in doses of 500 mg and 65 mg, respectively, per square meter of body surface area each on day 1 of a 3-week cycle. Patients with contraindications to administration of cisplatin, those who are intolerant to cisplatin, or develop grade 3 or 4 adverse events from cisplatin will be given carboplatin in combination with pemetrexed. Carboplatin will be given at a dose calculated to produce an area under the concentration-time curve (AUC) of 5.0mg/mL/min. Dose modifications of either pemetrexed or the platinum agent or both will be done in case of significant change in PS or toxicity from or intolerance to dose administered in the previous cycle.
Supplementation:
- Folic acid (FA) supplementation will be given to all patients orally in the dose of 5 ml (1000 μg) once daily of VITCOFOL (FDC Limited, Mumbai, India) pediatric formulation, which contains 200 μg FA/ml of the preparation. Patients will be instructed to measure the prescribed dose using a 5 ml plastic syringe containing markings at every 0.5 ml. Patients will also be instructed not to take any additional multivitamin supplements. In addition to FA supplementation, all patients will also be started simultaneously on oral iron (ferrous sulphate 200 mg twice a day). Once initiated, both FA and ferrous sulphate will be given on a daily basis and continued throughout the duration of chemotherapy and for at least 3 weeks beyond the last cycle.
- Vitamin B12 supplementation will be given to all patients intramuscularly in the dose of 1000 μg along with each cycle of chemotherapy (maximum of six doses during the study period).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 | Dietary Supplement: Folate and B12Participants are started on folate and vitamin B12 supplementation simultaneously with chemotherapy (within 24 hours of initiation of chemotherapy) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Folate and B12Vitamin (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. | Dietary supplement | Immediate Arm |
Primary outcome
Incidence of any grade hematological toxicity
Time frame: Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy
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
6 secondary outcomes
Incidence of grade 3/4 hematological toxicity
Time frame: 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
Time frame: Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy
Number of doses of ESAs administered
Time frame: Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy
Number of PRBC transfusions administered
Time frame: Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy
Relative Dose Intensity (RDI) delivered
Time frame: Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy
Number of Inter-Cycle Delays (ICDs)
Time frame: Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2017.
- Derived from this study: PubMed 30825389Singh 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.
- Derived from this study: PubMed 28073680Baldi 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Navneet Singh, MD DM principal investigator
PGIMER, Chandigarh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Folate and B12 in people with Lung Adenocarcinoma and Neutropenia, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of any grade hematological toxicity (time frame: Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02679443, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2017.