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High Dose Chemotherapy in Oligo-metastatic Homologous Recombination Deficient Breast Cancer (Oligo)

Primary Purpose

Breast Cancer

Status

Active

Phase

Phase 3

Locations

Netherlands

Study Type

Interventional

Intervention

carboplatin, thiotepa, and cyclophosphamide

chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine)

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring oligo metastatic, HRD deficiency

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Histologically or cytologically confirmed infiltrating breast cancer
Oligometastatic disease defined as one to three distant metastatic lesions, with or without primary tumor, local recurrence, or locoregional lymph node metastases, including the ipsilateral axillary, parasternal, and periclavicular regions. All lesions must be amenable to resection or radiotherapy with curative intent. Staging examinations must have included a PET-CT-scan and a MRI of the liver in case of liver metastases. Clustered lymph nodes that can be irradiated with curative intent in a single field are defined as a single lesion. Histologic or cytologic confirmation of at least one distant metastatic lesion is required.
No prior line of chemotherapy for metastatic disease (a maximum of 3 months of palliative endocrine therapy is allowed).
The tumor must be HER2-negative (either score 0 or 1 at immunohistochemistry or negative at in situ hybridization in case of score 2 or 3 at immunohistochemistry).
The tumor is deficient in homologous recombination and/or the patient has a deleterious germline BRCA1 or BRCA2 mutation.
At least stable disease of all tumor lesions after three courses of induction chemotherapy
Age ≥18 years
World Health Organisation (WHO) performance status 0 or 1
Adequate bone marrow function (ANC ≥1.0 x 109/l, platelets ≥100 x 109/l)
Adequate hepatic function (ALAT, ASAT and bilirubin ≤2.5 times upper limit of normal)
Adequate renal function (creatinine clearance ≥60 ml/min)
If clinically recommended echocardiography, MUGA, or MRI to evaluate if LVEF ≥50%;
Signed written informed consent
Able to comply with the protocol

Exclusion Criteria:

No malignancy other than breast cancer, unless treated with curative intent without the use of chemotherapy or radiation therapy
No current pregnancy or breastfeeding. Women of childbearing potential must use adequate contraceptive protection.
No concurrent anti-cancer treatment or investigational drugs

Sites / Locations

NKI-AVL

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

intensified alkylating chemotherapy

three cycles of chemotherapy

Arm Description

a course chemotherapy with high dose cyclophosphamide, G-CSF and peripheral blood progenitor cell (PBPC) harvest followed by tandem intermediate-dose alkylating therapy (miniCTC, carboplatin 800 mg/m2, thiotepa 240 mg/m2, and cyclophosphamide 3000 mg/m2) with PBPC-reinfusion.

three cycles of chemotherapy depending on previously received agents chemotherapy naïve;three cycles of docetaxel, doxorubicin, and cyclophosphamide previously received anthracyclines without taxanes;three cycles of carboplatin and paclitaxel previously received anthracyclines and taxanes;three cycles of carboplatin and gemcitabine

Outcomes

Primary Outcome Measures

Event free survival

time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first

Secondary Outcome Measures

Difference in median overall survival

time from randomization to death from any cause

Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0)

Difference in percentage of patients with grade >2 non-hematologic toxicity (CTCAE v4.0)

Difference in quality of life (EORTC QLQ-C30 v 3.0)

Difference in event free survival

o Difference in event free survival in the subgroups based on: Estrogen receptor status; Origin of the oligo-metastatic lesion (lymphnodes versus bone versus visceral metastases); Primary or recurrent oligometastatic breast cancer; BRCA1 mutation/profile or BRCA2 mutation/profile; HRD based on BRCA1 or BRCA2 mutation and HRD based on BRCA1-like and/or BRCA2-like profile.

Full Information

NCT ID

NCT01646034

First Posted

June 14, 2012

Last Updated

October 11, 2022

Sponsor

The Netherlands Cancer Institute

1. Study Identification

Unique Protocol Identification Number

NCT01646034

Brief Title

High Dose Chemotherapy in Oligo-metastatic Homologous Recombination Deficient Breast Cancer

Acronym

Oligo

Official Title

High-dose Alkylating Chemotherapy in Oligo-metastatic Breast Cancer Harboring Homologous Recombination Deficiency

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 2014 (undefined)

Primary Completion Date

January 2023 (Anticipated)

Study Completion Date

October 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The Netherlands Cancer Institute

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This study investigates the effect of high-dose alkylating chemotherapy compared with standard chemotherapy as part of a multimodality treatment approach in patients with oligo-metastatic breast cancer harboring homologous recombination deficiency.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

oligo metastatic, HRD deficiency

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

74 (Actual)

8. Arms, Groups, and Interventions

Arm Title

intensified alkylating chemotherapy

Arm Type

Experimental

Arm Description

Arm Title

three cycles of chemotherapy

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

carboplatin, thiotepa, and cyclophosphamide

Intervention Description

tandem intermediate-dose alkylating therapy: carboplatin 800 mg/m2, thiotepa 240 mg/m2, and cyclophosphamide 3000 mg/m2) with PBPC-reinfusion.

Intervention Type

Drug

Intervention Name(s)

chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine)

Intervention Description

chemotherapy naïve;three cycles of docetaxel, doxorubicin, and cyclofosfamide chemotherapy naïve;1 cycle of dose-dense Adriamycin and cyclophosphamide followed by 4 cycles of carboplatin and paclitaxel previously received anthracyclines without taxanes;three cycles of carboplatin and paclitaxel previously received anthracyclines and taxanes;three cycles of carboplatin and gemcitabine

Primary Outcome Measure Information:

Title

Event free survival

Description

time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first

Time Frame

assessed up to 120 months

Secondary Outcome Measure Information:

Title

Difference in median overall survival

Description

time from randomization to death from any cause

Time Frame

assessed up to 120 months

Title

Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0)

Description

Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0)

Time Frame

6 months after start of treament

Title

Difference in percentage of patients with grade >2 non-hematologic toxicity (CTCAE v4.0)

Description

Difference in percentage of patients with grade >2 non-hematologic toxicity (CTCAE v4.0)

Time Frame

6 months after start of treatment

Title

Difference in quality of life (EORTC QLQ-C30 v 3.0)

Description

Difference in quality of life (EORTC QLQ-C30 v 3.0)

Time Frame

6 and 12 months post treatment

Title

Difference in event free survival

Description

Time Frame

assessed up to 120 months

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically or cytologically confirmed infiltrating breast cancer Oligometastatic disease defined as one to three distant metastatic lesions, with or without primary tumor, local recurrence, or locoregional lymph node metastases, including the ipsilateral axillary, parasternal, and periclavicular regions. All lesions must be amenable to resection or radiotherapy with curative intent. Staging examinations must have included a PET-CT-scan and a MRI of the liver in case of liver metastases. Clustered lymph nodes that can be irradiated with curative intent in a single field are defined as a single lesion. Histologic or cytologic confirmation of at least one distant metastatic lesion is required. No prior line of chemotherapy for metastatic disease (a maximum of 3 months of palliative endocrine therapy is allowed). The tumor must be HER2-negative (either score 0 or 1 at immunohistochemistry or negative at in situ hybridization in case of score 2 or 3 at immunohistochemistry). The tumor is deficient in homologous recombination and/or the patient has a deleterious germline BRCA1 or BRCA2 mutation. At least stable disease of all tumor lesions after three courses of induction chemotherapy Age ≥18 years World Health Organisation (WHO) performance status 0 or 1 Adequate bone marrow function (ANC ≥1.0 x 109/l, platelets ≥100 x 109/l) Adequate hepatic function (ALAT, ASAT and bilirubin ≤2.5 times upper limit of normal) Adequate renal function (creatinine clearance ≥60 ml/min) If clinically recommended echocardiography, MUGA, or MRI to evaluate if LVEF ≥50%; Signed written informed consent Able to comply with the protocol Exclusion Criteria: No malignancy other than breast cancer, unless treated with curative intent without the use of chemotherapy or radiation therapy No current pregnancy or breastfeeding. Women of childbearing potential must use adequate contraceptive protection. No concurrent anti-cancer treatment or investigational drugs

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gabe S Sonke, MD

Organizational Affiliation

NKI-AVL, Amsterdam

Official's Role

Principal Investigator

Facility Information:

Facility Name

NKI-AVL

City

Amsterdam

ZIP/Postal Code

1066 CX

Country

Netherlands

12. IPD Sharing Statement

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High Dose Chemotherapy in Oligo-metastatic Homologous Recombination Deficient Breast Cancer

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