Malignant Childhood NeoplasmPhase 3NCT01858571
Low Dose Chemotherapy Versus Best Supportive Care in Progressive Pediatric Malignancies
A Phase 3 study testing Low dose chemotherapy in people with Malignant Childhood Neoplasm, run by All India Institute of Medical Sciences at 1 site in India.
Trial summary
Many of the pediatric malignancies are not curable on progression on front line or 2nd line chemotherapy. Further therapy with conventional drugs imposes many side effects and decreases the QOL. The usual therapy offered to such patients is best supportive care. Read more about this study
- Who is it for?
- Ages 5 to 18 years
- Conditions the study is for
- Malignant Childhood Neoplasm
- What is being tested?
- Low dose chemotherapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 108 participants
- Where
- 1 siteIndia
- Study dates
- Oct 2013to Jan 2017
- Phase
- Phase 3
- 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 5 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Refractory/Progressive non hematopoietic extracranial solid tumors following treatment with at least 2 lines of chemotherapy.
- ECOG performance status (<=3)(at least patients ambulating with crutches or on wheel chair)
- Age: 5-18 years
- Recovered from all acute toxic effects of earlier therapy
- Absolute neutrophil count > 1X 109/L
- Absolute platelet count > 75 x 109/L
- Normal renal functions
- Serum bilirubin <1.5 times the upper limit of normal, and the serum aspartate aminotransferase and alanine aminotransferase < 5 times the upper limit of normal.
Who cannot join
- Uncontrolled concurrent illness or active infection
- Positive serology for human immunodeficiency.
- Unable to swallow oral medication
- Pregnant and breast-feeding
Trial locations and contacts
1 site in 1 country.
India1 site
All India Institute of Medical Sciences
New Delhi, National Capital Territory of Delhi, 110029
About this study
Official title: Low Dose Chemotherapy (Metronomic Therapy) Versus Best Supportive Care in Progressive and/or Refractory Pediatric Malignancies: a Double Blind Placebo Controlled Randomized Study
Many of the pediatric malignancies are not curable on progression on front line or 2nd line chemotherapy. Further therapy with conventional drugs imposes many side effects and decreases the QOL. The usual therapy offered to such patients is best supportive care.
Metronomic chemotherapy can induce tumor stabilization or tumor responses in patients with cancer that are refractory or have relapsed after conventional chemotherapy. Whether metronomic therapy is better than best supportive care is not known. In order to do so, a study is required which may compare metronomic therapy with a placebo therapy on PFS and QOL in relapsed refractory cases of pediatric solid tumors who have failed at least two lines of chemotherapy.
Read more
HYPOTHESIS
The investigators hypothesize that metronomic chemotherapy in progressive pediatric malignancy will improve PFS and QOL. If validated, then this form for therapy will be an option for both the patients and the clinicians, who are left with just an option of best supportive care in such situations of progressive pediatric cancers despite multiple lines of chemotherapy.
Read the detailed description
Many of the pediatric malignancies are not curable on progression on front line or 2nd line chemotherapy. Further therapy with conventional drugs imposes many side effects and decreases the QOL. The usual therapy offered to such patients is best supportive care.
Metronomic chemotherapy can induce tumor stabilization or tumor responses in patients with cancer that are refractory or have relapsed after conventional chemotherapy. Whether metronomic therapy is better than best supportive care is not known. In order to do so, a study is required which may compare metronomic therapy with a placebo therapy on PFS and QOL in relapsed refractory cases of pediatric solid tumors who have failed at least two lines of chemotherapy.
It will be double blind randomized study. One group will receive metronomic therapy along with best supportive care and other will receive placebo and best supportive care.
The treatment will be continued till progression is documented. Metronomic chemotherapy schedule : Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) with each drug rounded off to the nearest tablet/capsule size.
Cycle A
- Daily oral Thalidomide (at 3mg/kg)
- Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
- Daily oral Etoposide (50 mg/m2/d) Cycle B
- Daily oral Thalidomide (at 3mg/kg)
- Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
- Daily oral Cyclophosphamide (2.5 mg/kg/d to a maximum of 100 mg/d) every 21 days
Placebo: Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration)
- Capsules of same size and color as used in metronomic therapy Best supportive care
- Management of pain as per WHO standard for pain management
The dose of medications in capsules have to be rounded off to the nearest capsule size. Instead of rounding off on the daily dose, the total dose over the week would be calculated and rounded off and divided over 5-6 days in a week. This is being done so as to prevent any extra dosing.
If any grade 3-4 toxicity occurs in the first course, then the dose for chemotherapy would be reduced in the subsequent course by 20%.
- Conditions
- Malignant Childhood Neoplasm
- Being tested
- Low dose chemotherapy
- Keywords
- Childhood Cancer
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low dose chemotherapyDrug
Also called •Thalidomide •Celecoxib •Etoposide •Cyclophosphamide
Metronomic chemotherapy schedule : Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) with each drug rounded off to the nearest tablet/capsule size.
Cycle A
- Daily oral Thalidomide (at 3mg/kg)
- Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
- Daily oral Etoposide (50 mg/m2/d)
Cycle B
- Daily oral Thalidomide (at 3mg/kg)
- Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
- Daily oral Cyclophosphamide (2.5 mg/kg/d to a maximum of 100 mg/d) every 21 days
| Study group | Role | What they receive |
|---|---|---|
| Low dose chemotherapy | Experimental | Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) with each drug rounded off to the nearest tablet/capsule size.
Cycle A
* Daily oral Thalidomide (at 3mg/kg)
* Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
* Daily oral Etoposide (50 mg/m2/d)
Cycle B
* Daily oral Thalidomide (at 3mg/kg)
* Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
* Daily oral Cyclophosphamide (2.5 mg/kg/d to a maximum of 100 mg/d) every 21 days Receives: Drug: Low dose chemotherapy |
| Best supportive care | Placebo comparator | Placebo: Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration)
* Capsules of same size and color as used in metronomic therapy Best supportive care
* Management of pain as per WHO standard for pain management Receives: Drug: Low dose chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Measured: Up to 2 years
Secondary outcomes (1)
Overall Survival
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2013 (estimated)
- Study startOct 2013
- Primary completionJul 2016
- Study completionJan 2017
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 Malignant Childhood NeoplasmStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- All India Institute of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sameer Bakhshi, All India Institute of Medical Sciences
- Investigators
- Sameer Bakhshi, MD, Principal investigator, All India Institute of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01858571
- Sponsor's protocol ID
- IEC/NP-63/2013
- Status last verified
- Jan 2017
- First submitted
- 17 May 2013
- Last updated
- 25 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Pramanik R, Agarwala S, Sreenivas V, Dhawan D, Bakhshi S. Quality of life in paediatric solid tumours: a randomised study of metronomic chemotherapy versus placebo. BMJ Support Palliat Care. 2023 Jun;13(2):234-237. doi: 10.1136/bmjspcare-2020-002731. Epub 2021 Jan 19.
PubMed 33468507Pramanik R, Agarwala S, Gupta YK, Thulkar S, Vishnubhatla S, Batra A, Dhawan D, Bakhshi S. Metronomic Chemotherapy vs Best Supportive Care in Progressive Pediatric Solid Malignant Tumors: A Randomized Clinical Trial. JAMA Oncol. 2017 Sep 1;3(9):1222-1227. doi: 10.1001/jamaoncol.2017.0324.
PubMed 28384657
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Dose Chemotherapy (Metronomic Therapy) Versus Best Supportive Care in Progressive and/or Refractory Pediatric Malignancies: a Double Blind Placebo Controlled Randomized Study
- ClinicalTrials.gov ID
- NCT01858571
- Acronym / sponsor ID
- IEC/NP-63/2013
- Conditions
- Malignant Childhood Neoplasm
- Keywords
- Childhood Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- All India Institute of Medical SciencesUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 21 May 2013 (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.
Many of the pediatric malignancies are not curable on progression on front line or 2nd line chemotherapy. Further therapy with conventional drugs imposes many side effects and decreases the QOL. The usual therapy offered to such patients is best supportive care.
Metronomic chemotherapy can induce tumor stabilization or tumor responses in patients with cancer that are refractory or have relapsed after conventional chemotherapy. Whether metronomic therapy is better than best supportive care is not known. In order to do so, a study is required which may compare metronomic therapy with a placebo therapy on PFS and QOL in relapsed refractory cases of pediatric solid tumors who have failed at least two lines of chemotherapy.
HYPOTHESIS
The investigators hypothesize that metronomic chemotherapy in progressive pediatric malignancy will improve PFS and QOL. If validated, then this form for therapy will be an option for both the patients and the clinicians, who are left with just an option of best supportive care in such situations of progressive pediatric cancers despite multiple lines of chemotherapy.
Detailed description
Many of the pediatric malignancies are not curable on progression on front line or 2nd line chemotherapy. Further therapy with conventional drugs imposes many side effects and decreases the QOL. The usual therapy offered to such patients is best supportive care.
Metronomic chemotherapy can induce tumor stabilization or tumor responses in patients with cancer that are refractory or have relapsed after conventional chemotherapy. Whether metronomic therapy is better than best supportive care is not known. In order to do so, a study is required which may compare metronomic therapy with a placebo therapy on PFS and QOL in relapsed refractory cases of pediatric solid tumors who have failed at least two lines of chemotherapy.
It will be double blind randomized study. One group will receive metronomic therapy along with best supportive care and other will receive placebo and best supportive care.
The treatment will be continued till progression is documented. Metronomic chemotherapy schedule : Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) with each drug rounded off to the nearest tablet/capsule size.
Cycle A
- Daily oral Thalidomide (at 3mg/kg)
- Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
- Daily oral Etoposide (50 mg/m2/d) Cycle B
- Daily oral Thalidomide (at 3mg/kg)
- Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg)
- Daily oral Cyclophosphamide (2.5 mg/kg/d to a maximum of 100 mg/d) every 21 days
Placebo: Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration)
- Capsules of same size and color as used in metronomic therapy Best supportive care
- Management of pain as per WHO standard for pain management
The dose of medications in capsules have to be rounded off to the nearest capsule size. Instead of rounding off on the daily dose, the total dose over the week would be calculated and rounded off and divided over 5-6 days in a week. This is being done so as to prevent any extra dosing.
If any grade 3-4 toxicity occurs in the first course, then the dose for chemotherapy would be reduced in the subsequent course by 20%.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low dose chemotherapy | Experimental | Drug: Low dose chemotherapyAlternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) with each drug rounded off to the nearest tablet/capsule size. Cycle A * Daily oral Thalidomide (at 3mg/kg) * Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg) * Daily oral Etoposide (50 mg/m2/d) Cycle B * Daily oral Thalidomide (at 3mg/kg) * Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg) * Daily oral Cyclophosphamide (2.5 mg/kg/d to a maximum of 100 mg/d) every 21 days |
| Best supportive care | Placebo comparator | Drug: Low dose chemotherapyPlacebo: Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) * Capsules of same size and color as used in metronomic therapy Best supportive care * Management of pain as per WHO standard for pain management |
Who may qualify
- Ages
- 5 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Refractory/Progressive non hematopoietic extracranial solid tumors following treatment with at least 2 lines of chemotherapy.
- ECOG performance status (<=3)(at least patients ambulating with crutches or on wheel chair)
- Age: 5-18 years
- Recovered from all acute toxic effects of earlier therapy
- Absolute neutrophil count > 1X 109/L
Key exclusion criteria (4 listed)
- Uncontrolled concurrent illness or active infection
- Positive serology for human immunodeficiency.
- Unable to swallow oral medication
- Pregnant and breast-feeding
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 |
|---|---|---|
| Low dose chemotherapyAlso: •Thalidomide •Celecoxib •Etoposide •CyclophosphamideMetronomic chemotherapy schedule : Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) with each drug rounded off to the nearest tablet/capsule size. Cycle A * Daily oral Thalidomide (at 3mg/kg) * Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg) * Daily oral Etoposide (50 mg/m2/d) Cycle B * Daily oral Thalidomide (at 3mg/kg) * Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg) * Daily oral Cyclophosphamide (2.5 mg/kg/d to a maximum of 100 mg/d) every 21 days | Drug | Best supportive care, Low dose chemotherapy |
Primary outcome
Progression free survival
Time frame: Up to 2 years
1 secondary outcome
Overall Survival
Time frame: Up to 2 years
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 Jan 2017.
- Derived from this study: PubMed 33468507Pramanik R, Agarwala S, Sreenivas V, Dhawan D, Bakhshi S. Quality of life in paediatric solid tumours: a randomised study of metronomic chemotherapy versus placebo. BMJ Support Palliat Care. 2023 Jun;13(2):234-237. doi: 10.1136/bmjspcare-2020-002731. Epub 2021 Jan 19.
- Derived from this study: PubMed 28384657Pramanik R, Agarwala S, Gupta YK, Thulkar S, Vishnubhatla S, Batra A, Dhawan D, Bakhshi S. Metronomic Chemotherapy vs Best Supportive Care in Progressive Pediatric Solid Malignant Tumors: A Randomized Clinical Trial. JAMA Oncol. 2017 Sep 1;3(9):1222-1227. doi: 10.1001/jamaoncol.2017.0324.
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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.
Sameer Bakhshi, MD principal investigator
All India Institute of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Low dose chemotherapy in people with Malignant Childhood Neoplasm, run by All India Institute of Medical Sciences 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 8 inclusion and 4 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 Jan 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Progression free survival (time frame: Up to 2 years). 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 NCT01858571, 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 Jan 2017.