Chronic Toxicities Related to Treatment in Patients With Localized Cancer (CANTO)

• ClinicalTrials.gov Identifier: NCT01993498
• Recruitment Status: Recruiting
• First Posted: November 25, 2013
• Last Update Posted: April 24, 2023
• Sponsor: UNICANCER
• Information provided by (Responsible Party): UNICANCER

Tracking Information

• First Submitted Date: October 17, 2013
• First Posted Date: November 25, 2013
• Last Update Posted Date: April 24, 2023
• Actual Study Start Date: February 20, 2012
• Estimated Primary Completion Date: March 2034 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 22, 2013): Evaluation of chronic toxicity in patients treated for non-metastatic breast cancer [ Time Frame: 8 years ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Chronic Toxicities Related to Treatment in Patients With Localized Cancer
• Official Title: A Cohort to Quantify and to Predict Treatment Related Chronic Toxicities in Patients With Non-metastatic Cancer - Breast and Lung.

Brief Summary

The aims of the cohort will be to quantify impact of cancer treatments toxicities , and to generate predictors of chronic toxicity in patients with non-metastatic cancer. Study of the original cohort will be focused on localized breast cancer patients, other localisation in non-metastatic setting will be explored furtherwise, fist of all in lung cancer.

The project will include four specific aims :

1. To develop a database of chronic treatment related toxicity in a cohort of 14750 women with stage I-III breast cancer (= non metastatic), whatever these treatments are (surgery; radiation therapy; chemotherapy …)
2. To describe incidence, clinical presentation, and outcome of chronic toxicities.
3. To describe the psychological, the social and the economic impacts of chronic toxicities.
4. To generate predictors for chronic toxicities in order to prevent them, based upon biological criteria.

The expected impact of these toxicities, when identified, will be to improve quality of life and to decrease health cost, by the early identification of patients at high risk of toxicity. Such early identification could lead to prevent toxic effect by: a. developing prevention strategies, b. substituting toxic treatment by a non (less) toxic one.

Also, such cohort will offer a quantification of the impact of treatment toxicity, that could be further used to quantify medical usefulness of strategies that aim at decreasing treatment toxicities (implementation of predictive biomarker for resistance, cytotoxic-free regimen etc…)

Detailed Description

SPECIFIC AIM I: TO DEVELOP A TOXICITY DATABASE ON A COHORT OF 20,000 WOMEN WITH STAGE I-III (NON METASTATIC) BREAST CANCER

Selection criteria The cohort will include female patients with non-metastatic breast cancer (stage I-III) without any selection based on their characteristics (except stage) or treatment. They may be included in other concomitant clinical studies.

Patients will have to sign informed consent and will have to benefit from social security.

The lack of selection criteria is related to the fact that the cohort aims at investigating toxicity in the whole population of breast cancer from a public health perspective.

Sample size The cohort plans to include 14750 women in 13 years. A cohort of 14750 patients will allow to detect a two fold increased in the risk of a specific toxicity in a homogenous subgroup.

As illustration, the study present a 90% power to detect whether a variable (age as example) observed in 50% of patients is associated with an increased risk of toxicity (heart toxicity) in a specific subgroup (Her2+++).

Development of the cohort The14750 patients will be recruited in 26 cancer centers, maximum in France. These patients will be followed for at least 5 years in the context of the cohort. After 5 years, additional specific data will then be captured each year.

Patients will be included at the time of diagnosis, before any cancer specific treatment. After having signed informed consent, the patient will fill a first questionnaire for demographics (adapted from French DREES reference study) and living conditions, and a set of validated questionnaires related to QoL and special psychological dimensions. In addition, blood samples will be collected at baseline.

The toxicities (events) will start to be collected 3 months after the end of "acute" treatment (surgery/adjuvant/chemotherapy/radiation therapy). Toxicity data will also be collected at the time of the last chemotherapy. Toxicities will be collected each 6 months, alternatively by a dedicated nurse and by the patient herself. Three sets of toxicities will be collected.

• First, predefined and previously described toxicities will be collected on dedicated items in the case report form.
• Second, unknown toxicities will be captured by the use of a patient's notebook where each patient will collect events and doctor' visits (general practitioner or organ specialist). This will allow capturing events that have not previously been associated with cancer treatment toxicities.
• Finally, objective measurements by paraclinic exams will be done. This includes yearly blood tests and a heart ultrasonography at 1 and 5 years.

In addition to the data collection, a baseline blood sample for genetic analyses will be done, and serum samples will be collected at baseline and yearly during 5 years (serum).

Outcome data will also be collected and will include metastatic relapse (+ site), locoregional relapse (+ site) and death.

SPECIFIC AIM II: TO DESCRIBE INCIDENCE, CLINICAL PRESENTATION, BIOLOGICAL CHARACTERISTICS AND OUTCOME OF CHRONIC TOXIC EVENTS

This specific aim will follow three goals :

• First, the investigators will describe the incidence of predefined chronic toxicities according to the treatment received.
• Second, the investigators will aim at identifying new treatment-related toxicities. This information will be captured through a dedicated notebook where each patient will report all health and social related events.
• Finally, the investigators will also assess the outcome of each adverse event, and try to develop some hypotheses to be addressed in further clinical trials.

SPECIFIC AIM III: TO DESCRIBE THE PSYCHOLOGICAL AND THE SOCIAL IMPACTS OF TOXIC EVENTS This specific aim will be split in two parts: a. to describe the psychological and the social impact to the patient, b. to describe the impact at the population level.

To describe psychological and social impact for the patient

Using robust well validated methods, subjective and objective dimensions of wellbeing will be investigated, that is: a. Quality of life b. Living conditions c. Psychosocial issues.

Quality of life Global perception of quality of life will be assessed through different survey

Social impact Living conditions will be assessed through a questionnaire derived from the French DRESS reference study on living conditions. The initial questionnaire was designed by DRESS to investigate the social, economical, professional condition two years after the diagnosis of cancer: back or abandonment of the initial professional/social activity, conversion, income trends, etc.

Psychological impact This part will focus on psychological functioning, including psychological impact of chronic toxicities and psychological impact of cancer itself. Psychological impact is mainly expected on emotional issues, cognitive disorders, body image and sexual disorders.

To describe the impact on the society This sub-aim will mainly focus on medico-economics and will assess the global impact of treatment toxicity on health economy. The quantification of costs related to toxicities is a major challenge since it could allow to identify avoidable major source of expenses and could allow better tailoring treatment accordingly. Specific partnerships are being developed with the French social security and other public/private partners in order to accurately quantify toxicity-related cost.

SPECIFIC AIM IV TO DEVELOP PREDICTORS FOR CHRONIC TOXICITIES In the present specific aim, the goal will be to develop molecular/biologic predictors for toxic events. In as many cases as possible, the investigators will split the cohort into a discovery set and a test set, or will identify a cross-validating series before doing analyses.

Ultimately, the goal is to develop multiparametric scores to predict the occurrence of toxicity.

Regarding molecular predictors, it is planned that 20 ml blood will be collected yearly. One sample at baseline will be dedicated to single nucleotide polymorphism (SNP) arrays and validation of candidate genetic variants.

A number of tests are already planned. First, we will investigate conventional biological parameters including endocrine tests (cortisolemia, TSH, estradiol levels, mullerian hormone…), metabolic test (including lipidemia), hematologic tests, liver function, immune function (assessed by lymphocyte counts). Second, more recent and under investigation tests will be added including troponin (heart failure), mullerian hormone, bone resorption markers (bone loss), RANK / RANKL, osteoprotegerin (bone loss).

Finally, it is planned to use the baseline sample for the discovery of genetic tests and to use the serum for the discovery of biochemical predictors.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Breast Cancer Nos Metastatic Recurrent

Intervention

Procedure: blood sampling

blood samples collection

Study Arms

breast cancer treatment + blood sampling

Standard treatment of breast cancer with intervention : samples collection

Intervention: Procedure: blood sampling

Publications *

• Soldato D, Havas J, Crane TE, Presti D, Lapidari P, Rassy N, Pistilli B, Martin E, Del Mastro L, Martin AL, Jacquet A, Coutant C, Cottu P, Merimeche A, Lerebours F, Tredan O, Vanlemmens L, Andre F, Vaz-Luis I, Di Meglio A. Coffee and tea consumption, patient-reported, and clinical outcomes in a longitudinal study of patients with breast cancer. Cancer. 2022 Oct 1;128(19):3552-3563. doi: 10.1002/cncr.34401. Epub 2022 Aug 1.
• Presti D, Havas J, Soldato D, Lapidari P, Martin E, Pistilli B, Jouannaud C, Emile G, Rigal O, Fournier M, Soulie P, Mouret-Reynier MA, Tarpin C, Campone M, Guillermet S, Martin AL, Everhard S, Di Meglio A. Factors associated with enrolment in clinical trials among women with early-stage breast cancer. ESMO Open. 2022 Jun;7(3):100513. doi: 10.1016/j.esmoop.2022.100513. Epub 2022 Jun 17.
• Baker JL, Di Meglio A, Gbenou AS, El Mouhebb M, Iyengar NM, Michiels S, Cottu P, Lerebours F, Coutant C, Lesur A, Tredan O, Vanlemmens L, Jouannaud C, Hrab I, Everhard S, Martin AL, Arveux P, Fabrice A, Vaz-Luis I, Jones LW. Association between physical activity and neoadjuvant chemotherapy completion and pathologic complete response in primary breast cancer: the CANTO study. Br J Cancer. 2022 Sep;127(5):886-891. doi: 10.1038/s41416-022-01870-y. Epub 2022 Jun 17.
• Di Meglio A, Havas J, Gbenou AS, Martin E, El-Mouhebb M, Pistilli B, Menvielle G, Dumas A, Everhard S, Martin AL, Cottu PH, Lerebours F, Coutant C, Lesur A, Tredan O, Soulie P, Vanlemmens L, Joly F, Delaloge S, Ganz PA, Andre F, Partridge AH, Jones LW, Michiels S, Vaz-Luis I. Dynamics of Long-Term Patient-Reported Quality of Life and Health Behaviors After Adjuvant Breast Cancer Chemotherapy. J Clin Oncol. 2022 Sep 20;40(27):3190-3204. doi: 10.1200/JCO.21.00277. Epub 2022 Apr 21.
• Vaz-Luis I, Di Meglio A, Havas J, El-Mouhebb M, Lapidari P, Presti D, Soldato D, Pistilli B, Dumas A, Menvielle G, Charles C, Everhard S, Martin AL, Cottu PH, Lerebours F, Coutant C, Dauchy S, Delaloge S, Lin NU, Ganz PA, Partridge AH, Andre F, Michiels S. Long-Term Longitudinal Patterns of Patient-Reported Fatigue After Breast Cancer: A Group-Based Trajectory Analysis. J Clin Oncol. 2022 Jul 1;40(19):2148-2162. doi: 10.1200/JCO.21.01958. Epub 2022 Mar 15.
• Di Meglio A, Charles C, Martin E, Havas J, Gbenou A, Flaysakier JD, Martin AL, Everhard S, Laas E, Chopin N, Vanlemmens L, Jouannaud C, Levy C, Rigal O, Fournier M, Soulie P, Scotte F, Pistilli B, Dumas A, Menvielle G, Andre F, Michiels S, Dauchy S, Vaz-Luis I. Uptake of Recommendations for Posttreatment Cancer-Related Fatigue Among Breast Cancer Survivors. J Natl Compr Canc Netw. 2022 Feb 7;20(13). doi: 10.6004/jnccn.2021.7051.
• Di Meglio A, Havas J, Soldato D, Presti D, Martin E, Pistilli B, Menvielle G, Dumas A, Charles C, Everhard S, Martin AL, Coutant C, Tarpin C, Vanlemmens L, Levy C, Rigal O, Delaloge S, Lin NU, Ganz PA, Partridge AH, Andre F, Michiels S, Vaz-Luis I. Development and Validation of a Predictive Model of Severe Fatigue After Breast Cancer Diagnosis: Toward a Personalized Framework in Survivorship Care. J Clin Oncol. 2022 Apr 1;40(10):1111-1123. doi: 10.1200/JCO.21.01252. Epub 2022 Jan 21.
• Caumette E, Vaz-Luis I, Pinto S, Havas J, Bovagnet T, Ruiz de Azua G, Di Meglio A, Martin AL, Everhard S, Cottu P, Vanlemmens L, Jouannaud C, Lerebours F, Dumas A, Menvielle G. The Challenge of Return to Work after Breast Cancer: The Role of Family Situation, CANTO Cohort. Curr Oncol. 2021 Oct 1;28(5):3866-3875. doi: 10.3390/curroncol28050330.
• Di Meglio A, Gbenou AS, Martin E, Pistilli B, Ligibel JA, Crane TE, Flaysakier JD, Minvielle E, Vanlemmens L, Guenancia C, Rigal O, Fournier M, Soulie P, Mouret-Reynier MA, Tarpin C, Boiffard F, Guillermet S, Everhard S, Martin AL, Giacchetti S, Petit T, Dalenc F, Rouanet P, Arnaud A, Andre F, Vaz-Luis I. Unhealthy behaviors after breast cancer: Capitalizing on a teachable moment to promote lifestyle improvements. Cancer. 2021 Aug 1;127(15):2774-2787. doi: 10.1002/cncr.33565. Epub 2021 Apr 22.
• Di Meglio A, Menvielle G, Dumas A, Gbenou A, Pinto S, Bovagnet T, Martin E, Ferreira AR, Vanlemmens L, Arsene O, Ibrahim M, Wassermann J, Martin AL, Lemonnier J, Del Mastro L, Jones LW, Partridge AH, Ligibel JA, Andre F, Michiels S, Vaz Luis I. Body weight and return to work among survivors of early-stage breast cancer. ESMO Open. 2020 Nov;5(6):e000908. doi: 10.1136/esmoopen-2020-000908.
• Pistilli B, Paci A, Ferreira AR, Di Meglio A, Poinsignon V, Bardet A, Menvielle G, Dumas A, Pinto S, Dauchy S, Fasse L, Cottu PH, Lerebours F, Coutant C, Lesur A, Tredan O, Soulie P, Vanlemmens L, Jouannaud C, Levy C, Everhard S, Arveux P, Martin AL, Dima A, Lin NU, Partridge AH, Delaloge S, Michiels S, Andre F, Vaz-Luis I. Serum Detection of Nonadherence to Adjuvant Tamoxifen and Breast Cancer Recurrence Risk. J Clin Oncol. 2020 Aug 20;38(24):2762-2772. doi: 10.1200/JCO.19.01758. Epub 2020 Jun 22.
• Kabore EG, Guenancia C, Vaz-Luis I, Di Meglio A, Pistilli B, Coutant C, Cottu P, Lesur A, Petit T, Dalenc F, Rouanet P, Arnaud A, Arsene O, Ibrahim M, Wassermann J, Boileau-Jolimoy G, Martin AL, Lemonnier J, Andre F, Arveux P. Association of body mass index and cardiotoxicity related to anthracyclines and trastuzumab in early breast cancer: French CANTO cohort study. PLoS Med. 2019 Dec 23;16(12):e1002989. doi: 10.1371/journal.pmed.1002989. eCollection 2019 Dec.
• Ferreira AR, Di Meglio A, Pistilli B, Gbenou AS, El-Mouhebb M, Dauchy S, Charles C, Joly F, Everhard S, Lambertini M, Coutant C, Cottu P, Lerebours F, Petit T, Dalenc F, Rouanet P, Arnaud A, Martin A, Berille J, Ganz PA, Partridge AH, Delaloge S, Michiels S, Andre F, Vaz-Luis I. Differential impact of endocrine therapy and chemotherapy on quality of life of breast cancer survivors: a prospective patient-reported outcomes analysis. Ann Oncol. 2019 Nov 1;30(11):1784-1795. doi: 10.1093/annonc/mdz298.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 14, 2022): 14750
• Original Estimated Enrollment (submitted: November 22, 2013): 20000
• Estimated Study Completion Date: March 2034
• Estimated Primary Completion Date: March 2034 (Final data collection date for primary outcome measure)

Eligibility Criteria

Patient with disease ( 14550)

Inclusion Criteria:

• Women,
• Aged 18 years and over,
• With an invasive breast cancer diagnosed by cytology or histology,
• Tumors cT0 to cT3, CN0-3,
• No clinical evidence of metastasis at the time of inclusion,
• Untreated including scored for breast cancer surgery in progress,
• Patient receiving a social security system,
• Patient mastering the French language,
• Free and informed consent for additional biological samples, different questionnaires and collecting information on resource usage.

• (Since february 2022) Patient :

  1. Age < 45 years at diagnostic
  2. Or CT2-3, cN0-3, HER2+(RH+or RH-) or RH-HER2-

Exclusion Criteria:

• Metastatic breast cancer,
• Local recurrence of breast cancer,
• History of cancer within 5 years prior to entry into the trial other than basal cell skin or carcinoma in situ of the cervix,
• Already received treatment for breast cancer ongoing,
• Blood transfusion performed for less than six months,
• Persons deprived of liberty or under supervision (including guardianship).

Healthy volunteers ( 200)

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Catherine Gaudin; (0)6 71 48 27 76 ext + 33; c-gaudin@unicancer.fr

Contact: Anne Laure Martin; (0)1 44 23 55 56; al-martin@unicancer.fr

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT01993498
• Other Study ID Numbers: UC-0140/1103 CANTO; 2011-A01095-36 ( Other Identifier: French Conpetant Authority )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.
• Access Criteria: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.

• Current Responsible Party: UNICANCER
• Original Responsible Party: Same as current
• Current Study Sponsor: UNICANCER
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Fabrice André; Gustave Roussy - Villejuif

• PRS Account: UNICANCER
• Verification Date: April 2023