Individualized Treatment Strategy for Patients With Metastatic Non-clear Cell Renal Cell Carcinoma

NCT ID: NCT04644432

Last Updated: 2020-11-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-06

Study Completion Date

2022-09-06

Brief Summary

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The purpose of the open-label INDIGO-study is to examine whether a first line individualized treatment strategy based on DNA and RNA analyses from the patient's tumor is feasible. Moreover, to involve the patient further in their treatment via patient-reported outcomes (PRO) measurements in a value-based healthcare setup with simultaneous analyses of the financial costs of this strategy.

The patients are assigned into 4 treatment arms according to the results of their DNA and RNA analyses. All patients receive electronic questionnaires regarding symptoms and side effects weekly and questionnaires regarding quality of life monthly. Based on each patient's answers of the questionnaires the patient receives advices in the app to reduce the symptoms and side effects or the patient is instructed to contact the hospital.

The hypothesis: Basing the choice of first-line treatment for DNA mutations and RNA profiles in a heterogeneous patient population increases the overall response rate for the total population to 30% compared to 10% for historical cohorts.

Detailed Description

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Conditions

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Metastatic Renal Cell Carcinoma Kidney Neoplasm Urologic Neoplasms Urogenital Neoplasms

Keywords

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non-clear cell renal cell carcinoma liquid biopsy patient reported outcomes gene expression

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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A - for patients with a DNA mutation that match a targeted treatment

Listed below are the possible study drugs and dosages:

Erlotinib 150 mg once a day for 4 weeks.

Osimertinib 80 mg once a day for 4 weeks.

Alectinib 600 mg twice a day for 4 weeks

Dabrafenib 150 mg twice a day combined with Trametinib 2 mg once a day for 4 weeks

Trastuzumab-emtansin iv infusion 3.6 mg/kg every 3rd week

Olaparib 400 mg twice a day for 4 weeks

Pembrolizumab iv infusion 2 mg/kg every 3rd week

Cabozantinib 60 mg once a day for 4 weeks

Crizotinib 250 mg twice a day for 4 weeks

Palbociclib 125 mg once a day in3 weeks, hereafter pause for one week

Imatinib 400 mg once a day for 4 weeks

If the patient can fit in several arms, arm A or the arm closest to arm A is chosen.

Group Type EXPERIMENTAL

Medication (A specification is listed under each arm)

Intervention Type DRUG

Study drugs and dosages are listed in the description of arms.

Patient reported outcomes measurement

Intervention Type OTHER

PRO questionnaires regarding symptoms and side effects with questions selected from the Nation Cancer Institute Patient Reported Outcomes-Common Terminology Criteria for Adverse Events.

The patient receive individual advices according to the patient's answers to reduce the symptoms and side effects or is instructed to contact the hospital.

For monitoring quality of life the EORTC QLQ-C30 is used. All questionnaires are in Danish.

B - for patients with an angiogen profile

Study drug: Sunitinib peroral tablet 50 mg once a day for 4 weeks, hereafter pause for 2 weeks (4/2 schedule or 2/1 schedule).

If the patient can fit in several arms, arm A or the arm closest to arm A is chosen.

Group Type EXPERIMENTAL

Medication (A specification is listed under each arm)

Intervention Type DRUG

Study drugs and dosages are listed in the description of arms.

Patient reported outcomes measurement

Intervention Type OTHER

PRO questionnaires regarding symptoms and side effects with questions selected from the Nation Cancer Institute Patient Reported Outcomes-Common Terminology Criteria for Adverse Events.

The patient receive individual advices according to the patient's answers to reduce the symptoms and side effects or is instructed to contact the hospital.

For monitoring quality of life the EORTC QLQ-C30 is used. All questionnaires are in Danish.

C - for patients with an immune profile

Study drug: Nivolumab iv infusion 6 mg/kg (max 480 mg) every 4th week.

If the patient can fit in several arms, arm A or the arm closest to arm A is chosen.

Group Type EXPERIMENTAL

Medication (A specification is listed under each arm)

Intervention Type DRUG

Study drugs and dosages are listed in the description of arms.

Patient reported outcomes measurement

Intervention Type OTHER

PRO questionnaires regarding symptoms and side effects with questions selected from the Nation Cancer Institute Patient Reported Outcomes-Common Terminology Criteria for Adverse Events.

The patient receive individual advices according to the patient's answers to reduce the symptoms and side effects or is instructed to contact the hospital.

For monitoring quality of life the EORTC QLQ-C30 is used. All questionnaires are in Danish.

D - for patients that have neither mutations nor an immune- or angiogen profile

Study drug: Nivolumab iv infusion 6 mg/kg (max 480 mg) every 4th week.

If the patient can fit in several arms, arm A or the arm closest to arm A is chosen.

Group Type EXPERIMENTAL

Medication (A specification is listed under each arm)

Intervention Type DRUG

Study drugs and dosages are listed in the description of arms.

Patient reported outcomes measurement

Intervention Type OTHER

PRO questionnaires regarding symptoms and side effects with questions selected from the Nation Cancer Institute Patient Reported Outcomes-Common Terminology Criteria for Adverse Events.

The patient receive individual advices according to the patient's answers to reduce the symptoms and side effects or is instructed to contact the hospital.

For monitoring quality of life the EORTC QLQ-C30 is used. All questionnaires are in Danish.

Interventions

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Medication (A specification is listed under each arm)

Study drugs and dosages are listed in the description of arms.

Intervention Type DRUG

Patient reported outcomes measurement

PRO questionnaires regarding symptoms and side effects with questions selected from the Nation Cancer Institute Patient Reported Outcomes-Common Terminology Criteria for Adverse Events.

The patient receive individual advices according to the patient's answers to reduce the symptoms and side effects or is instructed to contact the hospital.

For monitoring quality of life the EORTC QLQ-C30 is used. All questionnaires are in Danish.

Intervention Type OTHER

Other Intervention Names

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PRO

Eligibility Criteria

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Inclusion Criteria

1. Signed informed consent form must be obtained before any study-related procedures start.
2. The patient must be willing and able to follow the protocol.
3. Age ≥ 18 years
4. Histological biopsy-confirmed inoperable, locally advanced or metastatic non-cc RCC or 100% sarcomatoid tumour arising from the kidney found unsuited for surgery with a curative intent. Nephrectomy is not mandatory.

1. If the primary disease was diagnosed more than 1 year ago, a fresh medium needle biopsy must be collected to confirm the diagnosis and tissue must be collected for DNA and RNA analyses.
2. If a patient with inoperable relapse had a nephrectomy less than 1 year ago, and no tissue samples are stored in Dansk CancerBiobank, a fresh medium needle biopsy must be collected for DNA and RNA analyses.
3. In cases where metastatic disease was confirmed by biopsy more than 1 year ago without initiated treatment, the patient is offered a fresh medium needle biopsy, but this is not mandatory for inclusion.
4. If the patient had a nephrectomy using tissue from Dansk CancerBiobank and has been diagnosed with metastases within 1 year, the patient must be offered a fresh medium needle biopsy from a metastasis if the metastasis is easily accessible for biopsy, but a fresh biopsy is not mandatory for inclusion.
5. A medium needle biopsy is mainly taken from a metastasis, but biopsy from a renal tumour is allowed.
6. A biopsy may not be taken from bones as it cannot be used for molecular analysis.
7. If the primary tumour is a proven clear cell RCC, but the biopsy from a metastasis shows non-cc RCC, the patient can be included in the study.
5. Sufficient tissue for DNA analyses, corresponding to 10 slides and RNA analyses corresponding to 1000 tumour cells.
6. Females with a negative pregnancy test or of non-childbearing potential (menopausal, hysterectomy or ovariectomy) and non-breastfeeding.
7. Females of childbearing potential (\<2 years after last menstrual period) and males must use effective contraception (pills, intrauterine device, diaphragm or condom with spermicide or sterilisation).
8. Measurable disease (according to RECIST 1.1 criteria)
9. Karnofsky Performance status ≥ 70% / ECOG Performance status 0-2.
10. Life expectancy more than 3 months.
11. At baseline, the laboratory values must be: Haematology: Leukocytes ≥ 3.0 x 109/l, thrombocytes ≥ 100 x 109/l, haemoglobin ≥ 6.2 mmol/l.
12. Biochemistry: International Normalized Ratio (INR) ≤ 1.5, APTT ≤ 1.5 x upper limit of normal (ULN) Total bilirubin ≤ 1.5 x ULN, aspartate transaminase, alanine aminotransferase ≤ 2.5 x ULN for patients without liver metastases, ≤ 5 x ULN for patients with liver metastases. Estimated glomerular filtration rate (eGFR) \> 30.

Exclusion Criteria

1. Previous systemic treatment for metastatic RCC (including neoadjuvant treatment).
2. Former adjuvant treatment with immune checkpoint inhibitors.
3. Major surgical procedure, open surgical biopsy or significant trauma within 28 days prior to initiation.
4. Serious non-healing wound, ulcer or bone fracture.
5. Auto-immune disease or other condition requiring systemic treatment with either corticosteroids (prednisolone \> 10 mg/day or similar) or other immunosuppressive drugs
6. Metastases in the central nervous system (CNS). The patient must have an MRI scan (preferred) or CT scan of the brain (using contrast agent if possible) within 28 prior to initiation.
7. Seizures which cannot be managed with standard medical treatment.
8. If urine dipstick with protein ≥ 3+, urine must be collected over a period of 24 hours which must be \< 3.5 grams/day. If degree 2 proteinuria, urine must be collected over a period of 24 hours prior to each prescription.
9. Other malignancy within 5 years (except for curatively treated basal cell carcinoma of the skin and/or cervix carcinoma in situ).
10. Uncontrolled hypertension (≥ 150 mm Hg systolic and/or ≥ 100 mm Hg diastolic) despite maximum antihypertensive medical treatment.
11. Clinically significant (i.e. active) cardiovascular disease, such as cerebrovascular conditions (≤ 6 months), myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) congestive heart failure ≥ degree III or serious cardiac arrhythmia requiring medical treatment. Patients with well-managed Atrial fibrillation/ atrial flutter may be included.
12. Treatment using other investigational drugs or participation in other studies.
13. Previous or current other diseases, metabolic dysfunction, clinical findings on physical examination or clinical laboratory findings that give suspicion of a disease or condition that would contraindicate the use of an investigational drug or a patient with a high risk of treatment complications.
14. Patients where the investigator finds that patient compliance prevents safe completion of the treatment.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Herlev and Gentofte Hospital

OTHER

Sponsor Role lead

Responsible Party

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Ida Rasmussen

Principal investigator, MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ida Marie L Rasmussen, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Oncology, Herlev and Gentofte Hospital

Locations

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Department of Oncology, Herlev and Gentofte Hospital

Herlev, , Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Anne Kirstine H Moeller, MD, PhD

Role: CONTACT

Phone: +4538681083

Email: [email protected]

Jesper A Palshof, MD, PhD

Role: CONTACT

Phone: +4538686161

Email: [email protected]

Facility Contacts

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Anne Kirstine H Moeller, MD, PhD

Role: primary

Jesper A Palshof, MD, PhD

Role: backup

References

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Rasmussen IML, Soerensen AV, Moller AK, Persson GF, Palshof JA, Taarnhoj GA, Pappot H. Individualizing the Oncological Treatment of Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma by Using Gene Sequencing and Patient-Reported Outcomes: Protocol for the INDIGO Study. JMIR Res Protoc. 2022 Sep 15;11(9):e36632. doi: 10.2196/36632.

Reference Type DERIVED
PMID: 36107483 (View on PubMed)

Other Identifiers

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2019-001316-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PACTIUS

Identifier Type: OTHER

Identifier Source: secondary_id

GCP

Identifier Type: OTHER

Identifier Source: secondary_id

UR1909

Identifier Type: -

Identifier Source: org_study_id