This study will facilitate data collection of the long-term outcomes of pediatric subjects who have been treated in clinical trials with dabrafenib, trametinib or the combination, to assess the long-term effect on growth, development and general health of these subjects.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Oct 2019 → ongoing

Decision date (initial)

2024-07-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis pharma AG OMS ID: ORG-100003908

External identifiers

EU CT number

2023-509276-42-00

EudraCT number

2018-004459-19

ClinicalTrials.gov

NCT03975829

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy

To assess the long-term safety of treatment with dabrafenib, trametinib or the combination.

Secondary objectives 2

1. To assess the long-term effect of treatment with dabrafenib, trametinib or the combination on general health, growth, and development.
2. To assess efficacy as determined by institutional standard of care procedures.

Conditions and MedDRA coding

Children and Adolescents with Cancers Harboring V600 mutation.

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001147-PIP02-20, EMEA-001177-PIP01-11, EMEA-001147-PIP01-11, EMEA-001177-PIP02-20

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Written informed consent, according to local guidelines, signed by the subject and/or by the parents or legal guardian prior to any study related screening procedures are performed.
2. Current or prior participation in a Novartis sponsored study such as CTMT212X2101, CDRB436G2201, CDRB436A2102, regardless of current age and independent of study phase.
3. Parent study (or cohort of parent study) is planned to be closed.
4. Subject has demonstrated treatment compliance, as assessed by the Investigator, within the parent study protocol requirement(s).
5. Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures.
6. Subject is currently receiving treatment with dabrafenib and/or trametinib within a Novartis Sponsored Drug Development study (i.e. CTMT212X2101, CDRB436G2201, CDRB436A2102)
7. In the opinion of the Investigator is likely to benefit from continued treatment.
8. Does not require treatment with prohibited concomitant medications.

Exclusion criteria 7

1. Subject has participated in a combination trial where dabrafenib and/or trametinib was dispensed in combination with another study medication. (Exception: Patients who were on the chemotherapy arm of the CDRB436G2201 study are eligible for this study after crossing over into the experimental treatment arm of the CDRB436G2201 study or have discontinued the study treatment and are now in follow-up).
2. Subject has permanently discontinued from study treatment in the parent protocol due to any reason.
3. Treatment with dabrafenib and/or trametinib for the patient’s indication is approved for marketing and the appropriate dosage form is commercially available and reimbursed in the country.
4. Subject currently has unresolved drug related severe toxicities for which dabrafenib and/or trametinib dosing has been interrupted in the parent study. If the subject should meet criteria to resume treatment on the parent protocol then they may be eligible for enrolment in this study.
5. Women of childbearing potential, defined as all females physiologically capable of becoming pregnant, must continue to use highly effective form of birth control method (contraception) during the study and for 16 weeks after stopping treatment with trametinib monotherapy or dabrafenib in combination with trametinib, and 2 weeks after stopping treatment with dabrafenib monotherapy, whichever is longer. a. Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (i.e. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. b. Female bilateral tube ligation, female sterilization, surgically sterilized prior to the study (have had surgical bilateral oophorectomy with or without hysterectomy) or total hysterectomy at least six weeks before taking study treatment. In case of oophorectomy alone, only when reproductive status of woman has been confirmed by follow-up hormone level assessment. c. Sterilization (at least 6 months prior to screening) for male partners. The sterilized male partner should be the sole partner for that subject. d. For subjects on dabrafenib monotherapy / trametinib in combination with dabrafenib: Placement of a hormonal or non-hormonal intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year. e. For subjects on trametinib monotherapy: Use of oral (estrogen and progesterone), injected or implanted combined hormonal methods of contraception, or placement of an intrauterine device (IUD), or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Male subjects (including those that have had a vasectomy) not willing to use a condom during intercourse while taking trametinib and/or dabrafenib and for the period of 16 weeks (for patients taking trametinib only, or in combination) or 2 weeks (for patients taking dabrafenib only) following stopping of study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above. Notes: • Double-barrier contraception: condom and occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/cream/suppository) are not considered highly effective methods of contraception. • Hormonal-based methods (i.e. oral contraceptives) are not considered as highly effective methods of contraception for patients taking dabrafenib due to potential drugdrug interactions with dabrafenib. • If local regulations are more stringent than the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF
6. Lactating females who are actively breast feeding.
7. Concurrent participation in other clinical trials using experimental therapies.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. AEs, SAE, clinically significant changes in laboratory values and vital signs.

Secondary endpoints 2

1. Serial measurements of height, weight, skeletal maturation, sexual maturation and cardiac function.
2. Disease specific clinical benefit, as determined by investigator using institutional standard of care.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 8

Locations

10 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 132 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications