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

NCT04644432 | Unknown Phase 2 DMC

• 4 other identifiers: UR19092019-001316-38PACTIUSGCP
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Renal Cell Carcinoma; Kidney Neoplasm; Urologic Neoplasms; Urogenital Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Overall response rate (ORR)

  The total share of patients who have received treatment with complete and partial response assessed radiologically based on RECIST v.1.1.

  30 months

• Time to treatment failure (TTF)

  The time from start up day 1 until discontinuation of treatment, regardless of the reason.

  30 months

Secondary Outcomes (8)

• Overall Survival (OS)

  30 months

• Progression-Free Survival (PFS)

  30 months

• Disease Control Rate (DCR)

  30 months

• Response duration

  30 months

• Use of PRO tools

  30 months

Other Outcomes (1)

• Quality of life questionnaires EORTC QLQ-C30 (general quality of life questionnaire)

  36 months

Study Arms (4)

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

EXPERIMENTAL

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.

Drug: Medication (A specification is listed under each arm); Other: Patient reported outcomes measurement

B - for patients with an angiogen profile

EXPERIMENTAL

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.

Drug: Medication (A specification is listed under each arm); Other: Patient reported outcomes measurement

C - for patients with an immune profile

EXPERIMENTAL

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.

Drug: Medication (A specification is listed under each arm); Other: Patient reported outcomes measurement

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

EXPERIMENTAL

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.

Drug: Medication (A specification is listed under each arm); Other: Patient reported outcomes measurement

Interventions

Medication (A specification is listed under each arm) DRUG

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

A - for patients with a DNA mutation that match a targeted treatment; B - for patients with an angiogen profile; C - for patients with an immune profile; D - for patients that have neither mutations nor an immune- or angiogen profile

Patient reported outcomes measurement 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.

Also known as: PRO

A - for patients with a DNA mutation that match a targeted treatment; B - for patients with an angiogen profile; C - for patients with an immune profile; D - for patients that have neither mutations nor an immune- or angiogen profile

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form must be obtained before any study-related procedures start.
• The patient must be willing and able to follow the protocol.
• Age ≥ 18 years
• 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.
• 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.
• 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.
• A medium needle biopsy is mainly taken from a metastasis, but biopsy from a renal tumour is allowed.
• A biopsy may not be taken from bones as it cannot be used for molecular analysis.
• 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.
• Sufficient tissue for DNA analyses, corresponding to 10 slides and RNA analyses corresponding to 1000 tumour cells.
• Females with a negative pregnancy test or of non-childbearing potential (menopausal, hysterectomy or ovariectomy) and non-breastfeeding.
• 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).
• Measurable disease (according to RECIST 1.1 criteria)
• Karnofsky Performance status ≥ 70% / ECOG Performance status 0-2.
• Life expectancy more than 3 months.

You may not qualify if:

• Previous systemic treatment for metastatic RCC (including neoadjuvant treatment).
• Former adjuvant treatment with immune checkpoint inhibitors.
• Major surgical procedure, open surgical biopsy or significant trauma within 28 days prior to initiation.
• Serious non-healing wound, ulcer or bone fracture.
• Auto-immune disease or other condition requiring systemic treatment with either corticosteroids (prednisolone \> 10 mg/day or similar) or other immunosuppressive drugs
• 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.
• Seizures which cannot be managed with standard medical treatment.
• 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.
• Other malignancy within 5 years (except for curatively treated basal cell carcinoma of the skin and/or cervix carcinoma in situ).
• Uncontrolled hypertension (≥ 150 mm Hg systolic and/or ≥ 100 mm Hg diastolic) despite maximum antihypertensive medical treatment.
• 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.
• Treatment using other investigational drugs or participation in other studies.
• 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.
• Patients where the investigator finds that patient compliance prevents safe completion of the treatment.

Sponsors & Collaborators

• Herlev and Gentofte Hospital: lead

Study Sites (1)

Department of Oncology, Herlev and Gentofte Hospital

Herlev, 2730, Denmark

RECRUITING

Related Publications (1)

• 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.

  PMID: 36107483 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms

Interventions

Dosage Forms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Study Officials

• Ida Marie L Rasmussen, MD

  Department of Oncology, Herlev and Gentofte Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne Kirstine H Moeller, MD, PhD

CONTACT

+4538681083; anne.kirstine.hundahl.moeller@regionh.dk

Jesper A Palshof, MD, PhD

CONTACT

+4538686161; jesper.andreas.palshof@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator, MD

Study Record Dates

• First Submitted: October 30, 2020
• First Posted: November 25, 2020
• Study Start: March 6, 2020
• Primary Completion: September 6, 2022
• Study Completion: September 6, 2022
• Last Updated: November 25, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)