Common Protocol Template Breast Cancer Library V001

Common Protocol Template BC Library v001

Common Protocol Template Breast Cancer Library v001

Section in Common Protocol Template (CPT) / Library Content
3. Objectives and Endpoints (Main Body) / Objectives and corresponding endpoints for the breast cancer study
5. Study population / Inclusion criteria related type of participation and disease characteristics
Exclusion criteria related to medical conditions
11. References / Protocol references

3. Objectives and Endpoints

Primary/Secondary Objective / Primary/Secondary Endpoint
Efficacy Objectives and Endpoints: Objective Response Rate(ORR)
Limited to participants who achieved either a complete response (CR) or partial response (PR) during study intervention phase of study prior to subsequent therapy.
To compare study intervention [X] to comparator study intervention [y] or comparator study intervention [X] [plus placebo if randomized trials], on objective response rate. / Objective Response Rate (ORR) Endpoints
ORR can be assessed in single-arm trials. Requires a smaller population and can be assessed earlier, compared with survival trials. Effect is attributable directly to the drug, not the natural history of the disease.
ORR is measured by the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by investigator assessment, and/or by the investigator at the local site, or derived from the raw tumor data (from local site and/or central review).
Objective response rate (ORR) is defined as the percentage of measurable disease participants with advanced or metastatic cancer who have achieved either complete response (CR) or partial response (PR) to a therapeutic intervention in clinical trials of anticancer agents.

Overall survival (OS) Objectives

To compare study intervention [X] relative to comparator study intervention [Y] on overall survival (OS).
OR: For single arm studies:
To demonstrate efficacy of study intervention X on overall survival. / Overall survival (OS) Endpoints
Overall survival is length of time from [randomization/date of first dose] until the date of death from any cause.

Progression free survival (PFS) Objectives

To compare study intervention [X] relative to comparator study intervention [Y] on progression free survival (PFS)
OR For single arm studies:
To demonstrate efficacy of study intervention [X] on progression free survival. / Progression free survival (PFS) Endpoints
Progression free survival (PFS) is measured by the PFS per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by blinded independent central review, and/or by the investigator at local site, or derived from the raw tumor data (from local site and/or central review).
Determination of progression made by the investigator at the local site.
Determination of progression made by independent central review process.
Determination of progression derived from raw tumor data via algorithm.
Time to Progression (TTP) Objective
To compare [study intervention X] relative to [comparator study intervention Y] on time to progression (TTP). / Time to Progression (TTP) Endpoint
TTP is measured by time from randomization until objective tumor progression.

Disease control rate (DCR) Objective

To compare study intervention [X] relative to comparator study intervention [Y] on disease control rate (DCR). / Disease control rate (DCR) Endpoint
DCR is measured by the percentage of participants with a best overall confirmed response of CR or PR at any time plus SD ≥[XX] weeks from [start of study intervention/randomization] until disease progression or death due to any cause or the start of new anticancer therapy.
Time to response (TTR) Objective
To compare [study intervention X] relative to [comparator study intervention Y] on time to response (TTR). / Time to response (TTR) Endpoint
TTR is measured, for participants with a confirmed CR or PR, by the time from first dose to the first documented evidence of CR or PR.
Time to recurrence (TTRc) Objective
To compare [study intervention X] relative to [study intervention Y] on time to recurrence (TTRc). / Time to recurrence (TTRc) Endpoints
TTRc is measured as the time from randomization to breast cancer recurrence;
Ignoring second primary cancers (including contralateral breast cancers and non breast second malignancies) and counting deaths without recurrence as a competing risk.
Time to distant recurrence (TTDR) Objective
To compare [study intervention X] relative to [study intervention Y] on time to distant recurrence (TTDR). / Time to distant recurrence (TTDR) Endpoints
TTDR is measured as the time from randomization to distant breast cancer recurrence;
ignoring second primary cancers (including contralateral breast cancers and non breast second malignancies) and counting deaths without recurrence as a competing risk.
Pathologic complete response (pCR) Objective
To compare [study intervention X] relative to [study intervention Y] on pathologic complete response (pCR) rate. / Pathologic complete response (pCR) Endpoints
pCR is measured as pathological complete response rates at the time of definite surgery according to NSABP guidelines.
pCR will be considered as a binary variable of ‘response’ versus ‘non-response’.
Event-Free Survival (EFS) Objective
To compare background therapy plus [study intervention X] relative to background therapy [plus placebo] on event-free survival.
OR for single arm studies:
To compare [study intervention X] on event free survival. / Event-Free Survival (EFS) Endpoint
Event free survival (EFS) is the length of time from [start date] until either death or until progression of the disease occurs[start date] that precludes surgery, including both local and distant recurrence.
Disease free survival (DFS) Objective
To compare background therapy plus [study intervention X] relative to background therapy [plus placebo] on disease-free survival.
OR for breast cancer types/stages that do not have background therapy (eg TNBC palliative care) or any single arm studies:
To demonstrate efficacy of [study intervention X] on disease free survival. / Disease free survival (DFS) Endpoints
Disease free survival is the length of time from [start date] until the patient survives without any evidence of disease recurrence [<define by protocol] or death.
Duration of Response (DOR) Objective
To compare background therapy plus [study intervention X] relative to background therapy [plus placebo] on duration of response.
Or for single arm studies:
To demonstrate efficacy of [study intervention X] on duration of response. / Duration of Response (DOR) Endpoints
Response or determination of progression made by the investigator at the local site
Response or determination of progression made by independent central review process
Response or determination of progression derived from raw tumor data via algorithm
Limited to participants who achieved either a CR or PR during dosing phase of study
Duration of response (DOR) is measured from the time that criteria are met for complete response (CR) or partial response (PR), [identified by RECIST 1.1/protocol defined criteria>] until the first date that recurrent or progressive disease is objectively documented
Best Overall Response (BOR) Objectives
Limited to participants who have measurable disease
To compare background therapy plus [study intervention X] relative to background therapy [plus placebo] on best overall response.
Or for single arm studies:
To demonstrate efficacy of [study intervention X] on best overall response. / Best Overall Response (BOR) Endpoints
Best response from start of trial until death or determination of recurrence or progression made by the investigator at the local site
Best response from start of trial until death or determination of recurrence or progression made by independent central review process
Best response from start of trial until death or determination of recurrence or progression derived from raw tumor data via algorithm
Best overall response (BOR) is defined as the best response recorded from the start of the trial, normally the date of randomization, until disease progression occurs (identified by [RECIST/protocol defined criteria] or death, or the patient discontinues study intervention.
Secondary Objective / Secondary Endpoint
Molecular biomarkers for clinical response or resistance Objective
To demonstrate the predictive value of [x] biomarker for clinical responsiveness or resistance. / Molecular biomarkers for clinical response or resistance Endpoint
This endpoint is measured by the relationship of biomarker [x] with clinical responsiveness or resistance.
Change in molecular biomarkers for clinical outcome Objective
To demonstrate a change in value of [x] biomarker correlates with clinical outcome. / Endpoint biomarker measured by change
This endpoint is measured by a change in biomarker [x] either 1) on study intervention or 2) at disease progression correlates with clinical outcome.
Patient-reported Outcomes Endpoints
To describe the changes of Patient Reported Outcomes (PRO) and Health-Related Quality of Life (HRQOL) within the study population and to describe the differences of PRO /HRQOL between study intervention groups. / Patient-reported Outcomes Endpoints
This endpoint is measured by changes from baseline in PRO and HRQOL scores and for each study arm
PRO for example Functional Assessment of Cancer Therapy – Breast (FACT-B) and Multidimensional Assessment of Fatigue (MAF) Scale.
Safety Objectives
The secondary objective of this trial is to compare the incidence of [X] safety event in patients treated with [study intervention X] relative to [comparator [study intervention Y] / Safety Event Endpoints
This endpoint is measured by the incidence of [X] safety events in each study intervention group.
Time to occurrence of [x] safety event may be included as part of this endpoint.

5. Study Population

5.1 Inclusion Criteria

Type of participant and disease characteristics

Histologically or cytologyically confirmed [x] breast cancer.

Instructional text specific to defined breast cancer type.

Breast cancer types as classified by pathologic and clinical assessment per regionally/locally recognized guidelines (i.e., American Society for Clinical Oncology [ASCO] CAP, European Guidelines for Breast Cancer Screening and Diagnosis etc).
Measurable disease, i.e., presenting with at least one measureable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Documented disease progression (i.e., based on radiographic imaging) following [x] line anti cancer systemic study intervention or documented radiological disease progression during the most recent cancer study intervention regimen.
Known hormone receptor status (ER/PgR or ER alone).
Documentation of [x] biomarker overexpression/amplification.

Instructional text specific to this inclusion criteria biomarker overexpression/amplification.

Overexpression/amplification as defined by recognized definition/consensus.

Eastern Cooperative Oncology Group (ECOG) performance status [x].

5.2. Exclusion Criteria

Concurrent medical conditions/history

Previous (less than 10 years) or current history of malignant neoplasm, except for:

Exceptions listed i.e. curative, basal cell carcinoma etc

If the protocol is to be conducted in a relapsed/refractory population. Replace [X] with malignancy under study.

Prior malignancy other than [X].
Other concurrent serious medical conditions that may interfere with planned study intervention.

11. References

Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
Burstein HJ, Harris JR, Morrow M. Malignant tumors of the breast. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2011.
Schwartz TL, Mogal H, Papageorgiou C, Veerapong J, Hsueh EC. Metaplastic breast cancer: histologic characteristics, prognostic factors and systemic treatment strategies. Exp Hematol Oncol. 2013;2(1):31. doi:10.1186/2162-3619-2-31.
Breast Cancer. Merck Manuals Professional Edition. Published October 2013. Accessed February 24, 2015.
Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE. Cancer of the Breast. Abeloff’s Clinical Oncology. 5th ed. New York: Churchill Livingstone; 2014.