A clinical study to investigate the safety and efficacy of RXDX-101 in patients with locally Advanced or Metastatic Cancer

• Register: EUCTR
• Last refreshed on: 22 November 2021
• Main ID: EUCTR2014-001326-15-ES
• Date of registration: 04/07/2014
• Prospective Registration: Yes
• Primary sponsor: Ignyta Inc.
• Public title: A clinical study to investigate the safety and efficacy of RXDX-101 in patients with locally Advanced or Metastatic Cancer
• Scientific title: A Phase 1/2a, Multicenter, Open-Label Study of Oral RXDX-101 in Adult Patients with Locally Advanced or Metastatic Cancer Confirmed to be Positive for TrkA, TrkB, TrkC, ROS1, or ALK Molecular Alterations
• Date of first enrolment: 15/10/2014
• Target sample size: 124
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001326-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Italy, Korea, Republic of, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Ignyta Inc.

• Name: Clinical Trial Information Desk
• Affiliation: Ignyta Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Willing and able to provide written IRB/IEC-approved Informed Consent.

2. Have histologically or cytologically confirmed diagnosis of relapsed or refractory locally advanced or metastatic solid tumors that have a TrkA, TrkB, TrkC, ROS1, or ALK molecular alteration (as defined in Section 7.1) and for whom no alternative effective standard therapy is available or for whom standard therapy is considered unsuitable or intolerable.

For Phase 2a: Patients with locally advanced or metastatic solid tumors that have:
? Cohort #1: a TrkA molecular alteration.
? Cohort #2: a TrkB or TrkC molecular alteration.
? Cohort #3: a ROS1 molecular alteration.
? Cohort #4a: patients with locally advanced or metastatic solid tumors that have an ALK molecular alteration who are naïve to prior treatment with ALK inhibitors (patients with locally advanced or metastatic non-small cell lung cancer who have not received prior therapy with crizotinib will be excluded) or who have failed prior treatment with a single ALK inhibitor, including those who did not tolerate crizotinib. If a patient is refractory to one or more ALK inhibitors, then the patient must undergo a tumor biopsy following failure to prior therapy.
? Cohort #4b: patients with locally advanced or metastatic solid tumors that have an ALK molecular alteration who have failed prior treatment with more than one ALK inhibitor. If a patient is refractory to one or more ALK inhibitors, then the patient must undergo a tumor biopsy following failure to prior therapy.

3. Tumor tissue available for analysis. Only non-CNS lesions may be re-biopsied and must incur minimal risk to patients (e.g., percutaneous biopsy).

4. Measurable disease according to RECIST version 1.1.

5. Prior cancer therapy is allowed, including crizotinib and investigational drugs. At the time of treatment start, at least 2-4 weeks must have elapsed after prior cytotoxic chemotherapy (at least 6 weeks for nitrosureas, mitomycin C and liposomal doxorubicin). In the absence of toxicity, 7 days must have elapsed since completion of prior non-cytotoxic cancer therapy.

6. Prior radiotherapy is allowed if >14 days have elapsed since end of treatment, provided that no more than 25% of bone marrow reserve has been irradiated.

7. Patients with controlled asymptomatic CNS involvement are allowed in absence of therapy with anticonvulsants. Patients not requiring or requiring steroids at stable dose (? 4 mg/day dexamethasone or equivalent) for at least 2 weeks are eligible.

8. Patients who have received brain irradiation must have completed whole brain radiotherapy and gamma knife at least 4 weeks prior to enrollment.

9. Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to NCI CTCAE (Version 4.03) Grade ? 1 or to the baseline laboratory values as defined in Inclusion Criterion Number 13.

10. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ? 2.

11. Adult patients (age ?18).

12. Life expectancy of at least 3 months.

13. Baseline laboratory values fulfilling the study requirements.

14. Females of child-bearing potential must have a negative serum pregnancy test during screening and be neither breastfeeding nor intending to become pregnant during study participation. Females of childbearing potential must agree to avoid pregnancy during the study and agree upon the use of effective contraceptive methods (hormonal or barrier method of birth control, or abstinenc
Exclusion criteria:
1. Current participation in another therapeutic clinical trial.
2. Known symptomatic brain metastases or leptomeningeal involvement as assessed by MRI or contrast CT scan examination. Patients with asymptomatic leptomeningeal carcinomatosis may be enrolled at the discretion of the Investigator.
3. History of previous cancer, except squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected, requiring therapy within the previous 3 years.
4. Incomplete recovery from any surgery prior to treatment.
5. Any of the following in the past 6 months: myocardial infarction, unstable angina, coronary/ peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, symptomatic bradycardia, requirement for anti-arrhythmic medication.
6. History of prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 450 milliseconds).
7. History of additional risk factors for torsade de pointes (e.g., heart failure, family history of long QT syndrome).
8. Use of concomitant medications (refer to Section 10 of protocol) that increase or possibly increase the risk to prolong the QTc interval and/or induce torsades de pointes ventricular arrhythmia.
9. Known active infections (bacterial, fungal, viral including HIV positivity).
10. Gastrointestinal disease (e.g., Crohn?s disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
11. Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis.
12. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study or could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
13. History of stroke or seizure.
14. Peripheral neuropathy ? Grade 1.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Locally advanced or metastatic solid tumors
MedDRA version: 17.0 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864
MedDRA version: 17.0 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: RXDX-101
Pharmaceutical Form: Capsule
INN or Proposed INN: RXDX-101
CAS Number: 1108743-60-7
Current Sponsor code: RXDX-101
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: RXDX-101
CAS Number: 1108743-60-7
Current Sponsor code: RXDX-101
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: RXDX-101
CAS Number: 1108743-60-7
Current Sponsor code: RXDX-101
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: Primary Objective of Phase 1 Dose Escalation:
The primary objective of the Phase 1 dose escalation segment is to determine the first cycle dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and a biologically effective and recommended Phase 2 dose (RP2D) of RXDX-101 orally administered once daily.

Primary Objective of Phase 2a Expansion:
The primary objective of the Phase 2a expansion cohorts is Objective Response (OR) defined as Complete Response (CR) and Partial Response (PR) at the RP2D of RXDX-101 orally administered once daily.

Primary end point(s): - Phase I
DLTs,(dose-limiting toxicities) MTD (maximum tolerated dose) and RP2D (recommended Phase 2 dose)

- Phase 2
OR (Objective Response) defined as Complete Response (CR) and Partial Response (PR) according to RECIST v1.1.
Measured by tumour imaging

Timepoint(s) of evaluation of this end point: - Phase I
First cycle

- Phase 2
Scr; D28-C2; D28 each cycle; EoT

Secondary Objective: Phase 1 dose escalation.To assess:
- Safety profile of RXDX-101
- Pharmacokinetics
- Antitumor activity
- Assay methods to detect TrkA, TrkB, TrkC, ROS1, and ALK molecular alterations, identify appropriate analytical cutoffs, and other relevant biomarker parameters
- Pharmacodynamics of RXDX-101 on molecular targets in tumor and surrogate tissue

Phase 2a segment .To assess:
-Progression-Free Survival
-Overall Survival
- Disease Control
- Duration of response
- Intracranial tumor response for patients with brain metastases
- Safety and tolerability of RXDX-101
- Assay methods to detect TrkA, TrkB, TrkC, ROS1, and ALK molecular alterations; identification of appropriate analytical cutoffs and other relevant biomarker parameters
- Pharmacodynamics of RXDX-101 on molecular targets in tumor and surrogate tissue
- Pharmacokinetics of RXDX-101 and metabolites in plasma

Secondary Outcome(s)

Secondary end point(s): - Phase I
1. Adverse events
2. Clinical safety lab test (blood, urine)
3. Vital signs, weight performance
4. ECG
5. Physical examination
6. Pharmacokinetics (PK)
7. Objective Response (OR)
8. Progression-Free Survival (PFS)
9. Overall Survival (OS)
10. Disease Control (DC)
11. Duration of response (DOR)
12. Pharmacodynamics (PD)

- Phase 2
1. Adverse events
2. Clinical safety lab test (blood, urine)
3. Vital signs, weight performance
4. ECG
5. Physical examination
6. Progression-Free Survival (PFS)
7. Overall Survival (OS)
8. Disease Control (DC)
9. Duration of response (DOR)
10. Intracranial tumour response
11. Pharmacodynamics (PD)
12. Pharmacokinetics (PK)

Timepoint(s) of evaluation of this end point: Ph I
1.V1-C1 to VFU
2.Scr; each D-C1,C2; D14, 28-each C;EoT
3.Scr; D1 to 28, 42-C1; D28-C2; D28-each C;EoT
4.Scr; D1, 7,D42-C1; D28-C2; D28-each C;EoT
5.Scr; each D-C1; D28-C2; D28 each C;EoT
6.D1,7,14,28, 35,42-C1
7,8 Scr; D28-C2; D28 each C;EoT
9. 1st dose to death
10,11.Scr, D28-C2; D28 each C;EoT
12 D1 to 28-C1; C2D28;EoT

Ph2
1.V1-C1 to VFU
2.Scr; D1 to 28-C1; each D-C2; D14, 28-each C;EoT
3.Scr; D1 to 28-C1; 28-C2; D28-each C;EoT
4.Scr; D1, 7,28-C1; D28-C2; D28-each C;EoT
5.Scr; D1 to 28-C1; D28-C2; D28 each C;EoT
6.Scr,D28-C2; D28 each C;EoT
7.1st dose to death
8,9,10. Scr, D28-C2; D28 each C;EoT
11.D1,7,14,28-C1; D28-C2;EoT
12.D1,7,14,28-C1

Secondary ID(s)

RXDX-101-01

Source(s) of Monetary Support

Ignyta, Inc.

Ethics review

Status: Approved
Approval date: 07/10/2014
Contact:

Results

• Results available: Yes
• Date Posted: 12/06/2021
• Date Completed: 02/06/2020
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001326-15/results