## Protocol Section
### Identification Module
**NCT ID:** NCT01896479

**Acronym:** EXAMINER

**Brief Title:** A Study of Two Different Doses of Cabozantinib (XL184) in Progressive, Metastatic Medullary Thyroid Cancer

**Official Title:** A Randomized, Double-blind Study To Evaluate the Efficacy and Safety of Cabozantinib (XL184) at 60 mg/Day Compared to a 140 mg/Day in Progressive, Metastatic Medullary Thyroid Cancer Patients

#### Organization Study ID Info
**ID:** XL184-401
#### Organization
**Class:** INDUSTRY
**Full Name:** Exelixis
### Status Module
#### Completion Date
**Date:** 2023-12

**Type:** ESTIMATED

#### Disp First Post Date
**Date:** 2021-07-26

**Type:** ACTUAL

**Disp First Submit Date:** 2021-07-13
**Disp First Submit QC Date:** 2021-07-20

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-07-12

**Type:** ACTUAL

**Last Update Submit Date:** 2023-07-07

**Overall Status:** ACTIVE_NOT_RECRUITING

#### Primary Completion Date
**Date:** 2020-07

**Type:** ACTUAL

#### Start Date
**Date:** 2014-12

**Status Verified Date:** 2023-07

#### Study First Post Date
**Date:** 2013-07-11
**Type:** ESTIMATED
**Study First Submit Date:** 2013-07-08
**Study First Submit QC Date:** 2013-07-08
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Exelixis

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The objective of this study is to evaluate the efficacy and safety of oral cabozantinib at a 60 mg dose compared with a 140 mg dose in subjects with progressive, metastatic MTC. It will test if the lower dose results in similar progression free survival (PFS) and overall response rate (ORR) with fewer adverse events compared to the PFS, ORR and adverse events found in previous clinical trials of 140 mg.

### Conditions Module

**Conditions:**

- Medullary Thyroid Cancer

**Keywords:**

- thyroid cancer

- medullary thyroid cancer

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 247

**Type:** ACTUAL

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Cabozantinib (XL184) 140 mg as capsules and placebo tablets administered orally once a day.

**Intervention Names:**

- Drug: Cabozantinib (XL184) 140 mg

- Drug: Placebo tablet

**Label:** Cabozantinib (XL184) 140 mg

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Cabozantinib (XL184) 60 mg as tablets and placebo capsules administered orally once a day.

**Intervention Names:**

- Drug: Cabozantinib (XL184) 60 mg

- Drug: Placebo capsule

**Label:** Cabozantinib (XL184) 60 mg

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Cabozantinib (XL184) 140 mg

**Name:** Cabozantinib (XL184) 140 mg

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Cabozantinib (XL184) 60 mg

**Name:** Cabozantinib (XL184) 60 mg

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Cabozantinib (XL184) 140 mg

**Name:** Placebo tablet

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

- Cabozantinib (XL184) 60 mg

**Name:** Placebo capsule

**Type:** DRUG

### Outcomes Module

#### Other Outcomes

**Description:** Adverse events are measured from informed consent and at least through 30 days after the date of a decision to discontinue study treatment. Assessed for up to 31 months.

**Measure:** Safety and tolerability of cabozantinib as assessed by adverse events.

**Time Frame:** Up to 31 months

#### Primary Outcomes

**Description:** PFS is measured from randomization until the date of first documented disease progression or date of death from any cause, whichever comes first. Assessed for up to 31 months.

**Measure:** Progression Free Survival

**Time Frame:** Up to 31 months

#### Secondary Outcomes

**Description:** ORR is the proportion of subjects with measurable disease at baseline and who experience a best overall response of complete response (CR) or partial response (PR) which is confirmed ≥ 28 days later. Assessed for up to 31 months.

**Measure:** Objective Response Rate

**Time Frame:** Up to 31 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. The subject has a histologically confirmed diagnosis of MTC.
2. All subjects will need to be tested for RET mutational status. If subjects do not have documentation confirming they have a RET mutation, a sample of their tumor (taken either during screening or from a procedure within 6 months prior to randomization) will need to be tested.
3. The subject has measurable disease per RECIST 1.1 that is metastatic as determined by the investigator based upon computerized tomography (CT), magnetic resonance imaging (MRI), PET scan, bone scan, or X-ray taken within 28 days before randomization.
4. The subject has documented worsening of disease (progressive disease) at screening as compared with a previous CT, PETor MRI scan, bone scan, or X-ray as determined by the investigator per RECIST 1.1 on qualifying screening images taken within 28 days prior to randomization as compared to previous images taken within 14 months before the qualifying screening images.
5. The subject has recovered to baseline or CTCAE v4.0 (Common Terminology Criteria for Adverse Events, version 4.0) ≤ Grade 1 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy.
6. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 at screening.
7. The subject has adequate organ and marrow function
8. The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
9. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment.

Exclusion Criteria:

1. The subject has previously received cabozantinib.
2. Receipt of any type of small molecule kinase inhibitor or hormonal therapy within 28 days or 5 half-lives of the compound or active metabolites, whichever is shorter, before randomization.
3. Receipt of any systemic anti-tumor therapy within 28 days of randomization (42 days for nitrosoureas or/ mitomycin C).
4. Receipt of any other type of investigational agent within 28 days of randomization.
5. Receipt of radiation therapy within 28 days (14 days for radiation for bone metastases) of randomization or radionuclide treatment within 42 days of randomization. Subject is ineligible if there are any clinically relevant ongoing complications from prior radiation therapy.
6. The subject has untreated and/or active (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) central nervous system (CNS) metastasis. Must have completed radiation therapy ≥ 28 days prior to randomization and be stable without corticosteroids or anti-convulsant treatment for ≥ 10 days.
7. Treatment at therapeutic doses with oral anticoagulants or platelet inhibitors (examples are warfarin and clopidogrel).
8. The subject has uncontrolled, significant intercurrent illness including, but not limited to, cardiovascular disorders, gastrointestinal disorders, active infections, non-healing wounds, recent surgery.
9. Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms within 28 days before randomization.
10. The subject is unable to swallow multiple tablets or capsules.
11. The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation.
12. The subject is pregnant or breastfeeding.
13. The subject has had a diagnosis of another malignancy within 2 years before randomization, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** St. Leonards

**Country:** Australia

**State:** New South Wales

**Zip:** 2065

**Location 2:**

**City:** Herston

**Country:** Australia

**State:** Queensland

**Zip:** 4006

**Location 3:**

**City:** Kurralta Park

**Country:** Australia

**State:** South Australia

**Zip:** 5037

**Location 4:**

**City:** Parkville

**Country:** Australia

**State:** Victoria

**Zip:** 3050

**Location 5:**

**City:** Québec

**Country:** Canada

**State:** Quebec

**Zip:** JIH 5N4

**Location 6:**

**City:** Toronto

**Country:** Canada

**Zip:** M5G 2M9

**Location 7:**

**City:** Osijek

**Country:** Croatia

**Zip:** 31000

**Location 8:**

**City:** Zagreb

**Country:** Croatia

**Zip:** 10000

**Location 9:**

**City:** Zagreb

**Country:** Croatia

**Zip:** 1000

**Location 10:**

**City:** Bordeaux

**Country:** France

**State:** Gironde

**Zip:** 33076

**Location 11:**

**City:** Angers

**Country:** France

**State:** Maine-et-Loire

**Zip:** 49933

**Location 12:**

**City:** Lyon

**Country:** France

**State:** Rhône

**Zip:** 69373

**Location 13:**

**City:** Villejuif

**Country:** France

**State:** Val-de-Marne

**Zip:** 94805

**Location 14:**

**City:** Dijon

**Country:** France

**Zip:** 21079

**Location 15:**

**City:** Paris

**Country:** France

**Zip:** 75013

**Location 16:**

**City:** Strasbourg Cedex

**Country:** France

**Zip:** 67065

**Location 17:**

**City:** Budapest

**Country:** Hungary

**Zip:** 1088

**Location 18:**

**City:** Debrecen

**Country:** Hungary

**Zip:** 4032

**Location 19:**

**City:** Jerusalem

**Country:** Israel

**Zip:** 91120

**Location 20:**

**City:** Petach Tikva

**Country:** Israel

**Zip:** 49100

**Location 21:**

**City:** Safed

**Country:** Israel

**Zip:** 13100

**Location 22:**

**City:** Catania

**Country:** Italy

**State:** CT

**Zip:** 95124

**Location 23:**

**City:** Roma

**Country:** Italy

**State:** RM

**Zip:** 00161

**Location 24:**

**City:** Sienna

**Country:** Italy

**State:** SI

**Zip:** 53100

**Location 25:**

**City:** Pisa

**Country:** Italy

**State:** Toscana

**Zip:** 56124

**Location 26:**

**City:** Milano

**Country:** Italy

**Zip:** 20133

**Location 27:**

**City:** Padua

**Country:** Italy

**Zip:** 35138

**Location 28:**

**City:** Torino

**Country:** Italy

**Zip:** 10153

**Location 29:**

**City:** Goyang

**Country:** Korea, Republic of

**State:** Gyeonggido

**Zip:** 410769

**Location 30:**

**City:** Seoul

**Country:** Korea, Republic of

**Zip:** 110744

**Location 31:**

**City:** Seoul

**Country:** Korea, Republic of

**Zip:** 135-710

**Location 32:**

**City:** Amsterdam

**Country:** Netherlands

**State:** Noord Holland

**Zip:** 1066 CX

**Location 33:**

**City:** Leiden

**Country:** Netherlands

**State:** Zuid-Holland

**Zip:** 2333 ZA

**Location 34:**

**City:** Groningen

**Country:** Netherlands

**Zip:** 9713 GZ

**Location 35:**

**City:** Gliwice

**Country:** Poland

**State:** Slaskie

**Zip:** 44-100

**Location 36:**

**City:** Poznań

**Country:** Poland

**State:** Wielkopolskie

**Zip:** 60-355

**Location 37:**

**City:** Bucharest

**Country:** Romania

**Zip:** 10825

**Location 38:**

**City:** Bucharest

**Country:** Romania

**Zip:** 11863

**Location 39:**

**City:** Cluj-Napoca

**Country:** Romania

**Zip:** 400058

**Location 40:**

**City:** Timisoara

**Country:** Romania

**Zip:** 300723

**Location 41:**

**City:** Novosibirsk

**Country:** Russian Federation

**Zip:** 630068

**Location 42:**

**City:** Obninsk

**Country:** Russian Federation

**Zip:** 249036

**Location 43:**

**City:** St. Petersburg

**Country:** Russian Federation

**Zip:** 197089

**Location 44:**

**City:** Yaroslavl

**Country:** Russian Federation

**Zip:** 150040

**Location 45:**

**City:** Barcelona

**Country:** Spain

**Zip:** 08035

**Location 46:**

**City:** Madrid

**Country:** Spain

**Zip:** 28034

**Location 47:**

**City:** Madrid

**Country:** Spain

**Zip:** 28046

**Location 48:**

**City:** Lund

**Country:** Sweden

**State:** Skane Ian

**Zip:** SE-22185

**Location 49:**

**City:** Uppsala

**Country:** Sweden

**State:** Uppsala Ian

**Zip:** 75185

### References Module

#### References

**Citation:** Capdevila J, Klochikhin A, Leboulleux S, Isaev P, Badiu C, Robinson B, Hughes BGM, Keam B, Parnis F, Elisei R, Gajate P, Gan HK, Kapiteijn E, Locati L, Mangeshkar M, Faoro L, Krajewska J, Jarzab B. A Randomized, Double-Blind Noninferiority Study to Evaluate the Efficacy of the Cabozantinib Tablet at 60 mg Per Day Compared with the Cabozantinib Capsule at 140 mg Per Day in Patients with Progressive, Metastatic Medullary Thyroid Cancer. Thyroid. 2022 May;32(5):515-524. doi: 10.1089/thy.2022.0027.

**PMID:** 35403447

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004700

- Term: Endocrine System Diseases

- ID: D000004701

- Term: Endocrine Gland Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000006258

- Term: Head and Neck Neoplasms

- ID: D000018358

- Term: Neuroendocrine Tumors

- ID: D000017599

- Term: Neuroectodermal Tumors

- ID: D000009373

- Term: Neoplasms, Germ Cell and Embryonal

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000000230

- Term: Adenocarcinoma

- ID: D000002277

- Term: Carcinoma

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009380

- Term: Neoplasms, Nerve Tissue

### Condition Browse Module - Browse Branches

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16718

- Name: Thyroid Diseases

- Relevance: HIGH

- As Found: Thyroid

- ID: M16723

- Name: Thyroid Neoplasms

- Relevance: HIGH

- As Found: Thyroid Cancer

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M20423

- Name: Carcinoma, Neuroendocrine

- Relevance: HIGH

- As Found: Medullary Thyroid Cancer

- ID: M7862

- Name: Endocrine System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7863

- Name: Endocrine Gland Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M9348

- Name: Head and Neck Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M20495

- Name: Neuroendocrine Tumors

- Relevance: LOW

- As Found: Unknown

- ID: M19845

- Name: Neuroectodermal Tumors

- Relevance: LOW

- As Found: Unknown

- ID: M20388

- Name: Neuroectodermal Tumors, Primitive

- Relevance: LOW

- As Found: Unknown

- ID: M12318

- Name: Neoplasms, Germ Cell and Embryonal

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M3585

- Name: Adenocarcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12325

- Name: Neoplasms, Nerve Tissue

- Relevance: LOW

- As Found: Unknown

- ID: T5651

- Name: Thyroid Cancer, Medullary

- Relevance: HIGH

- As Found: Medullary Thyroid Cancer

- ID: T4091

- Name: Neuroendocrine Tumor

- Relevance: LOW

- As Found: Unknown

- ID: T4092

- Name: Neuroepithelioma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000013964

- Term: Thyroid Neoplasms

- ID: D000018278

- Term: Carcinoma, Neuroendocrine

- ID: D000013959

- Term: Thyroid Diseases

### Misc Info Module

- Version Holder: 2024-05-24
