Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05284305 |
| Other study ID # |
INT82/21 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2022 |
| Est. completion date |
May 15, 2023 |
Study information
| Verified date |
January 2023 |
| Source |
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano |
| Contact |
Marco Fiore, MD |
| Phone |
+390223903234 |
| Email |
marco.Fiore[@]istitutotumori.mi.it |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Desmoid tumors (DT) are rare disease of intermediate malignancy with variable and often
unpredictable clinical course. There is a growing interest in defining potential risk of
recurrence or progression during or after pregnancy and in identifying potential obstetrical
risks and infertility rate of desmoid patients.
Aim of the study:
- to define the impact of pregnancy on diagnosis, progression and recurrence of DT;
- to define the risks related to DT of obstetrical risks and decisions to interrupt or
avoid pregnancy after the diagnosis of DT.
Description:
Background. Desmoid tumors (DT) are rare disease of intermediate malignancy with variable and
often unpredictable clinical course.
A significant proportion of female patients with a diagnosis of DT have a recent pregnancy
history and on the contrary, the diagnosis of DT is often made during gestation or shortly
thereafter. Understanding the behavior of desmoids during or after pregnancy is crucial to
define the safest management of the tumor itself and of the pregnancy.
Moreover, analyzing the impact of DT on decisions regarding the pregnancy (and in turn
fertility), we will be able to implement new tools assisting and counselling women with DT.
Aim of the study.
1. to define the management of DT in patients diagnosed with desmoid before pregnancy and
during pregnancy;
2. analyze the oncological outcome of desmoid patients during and after pregnancy;
3. assess potential obstetrical risks and decisions to interrupt or avoid pregnancy after
the diagnosis of DT
Study design. International multicentric retrospective observational study. Histology. Only
patients with histology-proven desmoids will be included. DT will be defined according to the
WHO classification. Patients with FAP-related DT will be included and analyzed separately,
while those affected by infantile fibromatosis or palmar/plantar fibromatosis will be
excluded.
Data collection.
- Clinicopathological data: age at diagnosis, size of DT at the time of initial
presentation (measured as longest diameter) and tumor site. The latest will be
classified as abdominal wall, extremity (including limb girdle), intrabdominal
(including visceral, pelvic and mesenteric), or other.
- Treatment details of primary and recurrent DT: active surveillance, surgery, radiation
therapy, isolated limb perfusion, and systemic therapies. Date of surgery and margin
status (defined as R2, R1 and R0 if respectively macroscopic, microscopic and no tumor
is found in the final pathological specimen) will be also recorded. The systemic
treatment will include: cytotoxic chemotherapy with any regimen of agents, antiestrogen
or LH-RH inhibitors, other hormonal therapy, anti-inflammatory drugs, and molecular
targeted therapy.
- Recurrence or progression of disease and time of last follow-up. Recurrence will be
defined as macroscopic relapse 6 months or later after complete resection, for those
patients undergoing surgery. Progression, stability, or regression (partial or complete)
will be defined according to RECIST criteria (version 1.1), whether spontaneous or in
the presence oftherapy, both for patients undergoing surgery and for those managed with
active surveillance.
- Number of pregnancies and abortions (spontaneous or induced). For eachevent: date of
delivery or abortion, type of delivery, pregnancy complications and labor complications
will be recorded. For women with a history of DT, the date and type of first treatment
after pregnancy will be also recorded, regardless of the initial approach (whether
surgical or conservative).
- Patient reported outcomes. Concept elicitation (CE) interviews will be used to explore
desmoid patients' perspectives on key disease-related symptoms and impacts. Qualitative
analysis will be performed to determine the relative frequency and disturbance of
symptoms and impacts as well as other characteristics of these concepts (including
desire and success of a pregnancy, anxiety to start a pregnancy with a diagnosis of DT).
A draft patient-reported outcome (PRO) scale will be developed and compared with the
available literature then developed and tested with cognitive interviewing. Information
from the interviews will be subsequently incorporated into the refined PRO scale.
The following questions will be included in a questionnaire in order to define the possible
effects of DT on pregnancy:
1. Have you had a pregnancy during or after your diagnosis of desmoid tumor? [if Yes,
eligible for Study population]
2. At the time of the desmoid diagnosis were you fertile? If so, please answer the
following questions: [If Yes, eligible for Screening population]
3. After the diagnosis of desmoid, have you decided to postpone a pregnancy?
4. If so, was this related to the diagnosis of desmoid?
5. After the diagnosis of desmoid have you interrupted a pregnancy?
6. If so, was this related to the diagnosis of desmoid?
7. After the diagnosis of desmoid, have you decided to avoid pregnancies?
8. If so, was this related to the diagnosis of desmoid?
Statistical analysis. Discrete variables will be described as medians with interquartile
range (IQR). Categorical variables will be described as totals and frequencies. Univariate
comparisons will be assessed using the chi-squared or Wilcoxon-rank sum test as appropriate.
Univariate and multivariate logistic regression models will be assessed to determine the
association of relevant baseline clinicopathological factors with pregnancy. Variables with
univariate significance (p<0.20) will be entered into the multivariate model in combination
with important clinical variables and confounders. "Disease progression during pregnancy"
will include both PD according to RECIST within 1 year after delivery in patients with
previous SD, and local recurrence detected during pregnancy or within 1 year after delivery.
"Time to progression during pregnancy" will be calculated from estimated date of beginning of
pregnancy (based on date of delivery or abortion) and first evidence of PD/LR. "Spontaneous
regression after PD during pregnancy" will be defined as RECIST MR or PR in the absence of
any active treatment after delivery regardless of previous "Disease progression during
pregnancy". For the purpose of the following outcomes "Disease progression during
pregnancy","Time to progression during pregnancy", "Spontaneous regression after PD during
pregnancy" estimates will be calculated based on the overall number of recorded pregnancies,
meaning that for a single patients it will be calculated for each pregnancy following the
diagnosis of DF. Survival adjusted for censoring will be calculated using the Kaplan-Meier
method and medians compared using the log-rank test.
All analyses will be carried out with STATA version 13.0 (StataCorp, College Station, TX),
and a P-value of <0.05 (two-tailed) will be considered statistically significant.
Expected Results. Although DT tend to grow during pregnancy, patients followed in specialized
sarcoma centers are safely managed. DT should not be considered a contraindication to
pregnancy, however patients need to be enrolled in a close follow-up program. The impact of
DT (and of the related management) on pregnant women and new mothers can translate in anxiety
for a new pregnancy, desire to avoid pregnancy, and other symptoms which will be recorded as
PRO.
Data Quality Control. Data quality will be guarantee by local Principal Investigators. In
particular a specific kickoff meeting will be organized providing instruction for all
Investigators. Data entry will be centralized by means of an online CRF, who will be
accessible to Investigators after a data transfer and use agreement (DTUA) between the
Promoter and the participating centers.
As far as data of patients enrolled by Desmoid Foundation Italia, data quality check will be
guarantee by supervision of the study PI.
