## Protocol Section
### Identification Module
**NCT ID:** NCT01652079

**Brief Title:** CRLX101 in Combination With Bevacizumab for Recurrent Ovarian/Tubal/Peritoneal Cancer

**Official Title:** A Phase II, 2-stage Trial of CRLX101 in Combination With Bevacizumab in Recurrent Platinum-Resistant Ovarian, Tubal and Peritoneal Cancer

#### Organization Study ID Info
**ID:** 11-485
#### Organization
**Class:** OTHER
**Full Name:** Massachusetts General Hospital
### Status Module
#### Completion Date
**Date:** 2018-03

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2018-07-02

**Type:** ACTUAL

**Last Update Submit Date:** 2018-06-28

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2018-03

**Type:** ACTUAL

#### Start Date
**Date:** 2012-04

**Status Verified Date:** 2018-06

#### Study First Post Date
**Date:** 2012-07-27
**Type:** ESTIMATED
**Study First Submit Date:** 2012-07-25
**Study First Submit QC Date:** 2012-07-25
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Massachusetts General Hospital

#### Responsible Party

**Investigator Affiliation:** Massachusetts General Hospital

**Investigator Full Name:** Richard Thomas Penson

**Investigator Title:** Principal Investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This research study is a Phase II clinical trial. In addition to studying safety, Phase II clinical trials test if the investigational drug is effective and whether the drug works in treating a specific cancer. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of cancer. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved CRLX101 for your type of cancer.

Camptothecin is a chemical extracted from plants that is the basis for the standard FDA-approved chemotherapy drugs irinotecan and topotecan. Camptothecin works by interfering with the way cells divide and multiply. The investigational drug CRLX101 is a formulation of camptothecin and a large molecule (nanoparticle)that appears to allow more of the camptothecin to get into tumors and stay in tumors. The persistence of the CRLX101 in the tumor may increase the probability that the tumor cells will be damaged.

CRLX101 has been well tolerated in the laboratory and in participants with different kinds of cancer.

Bevacizumab (Avastin) is a VEGF inhibitor which has activity in many kinds of cancer. Bevacizumab has been successfully combined with many chemotherapy partners.

It has been hypothesized that the combination of bevacizumab with CRLX101 might have unique clinical activity in combination in the treatment of this disease due to the simultaneous inhibition of distinct steps along the HIF → (CAIX) → VEGF → VEGFR2 pathway. Specifically, it is hypothesized that CRLX101-mediated inhibition of HIF-1α carries with it the potential to interrupt hypoxia and HIF-1α-associated resistance to VEGFR inhibitors. It is hoped that this combination will work to treat your type of cancer.

**Detailed Description:** You will receive CRLX101 and bevacizumab through an intravenous (IV) infusion once every 14 days. Each cycle is 28 days. You will continue to receive both drugs until you and/or the research doctor decides it may not be in your best interest to continue.

You will receive premedication including decadron, zantac and benadryl to help prevent an allergic reaction and nausea prior to your CRLX101 infusion.You will also receive IV fluid before and after the study drug administration to keep you hydrated. It will be important for you to drink water regularly in between study visits.You will be treated as an outpatient. At every clinic visit, you will undergo the following assessments: Medical history, physical examination, vital signs, performance status, routine blood tests, urine tests, assessment for any new side effects, CT evaluation (every 8 weeks).

You will have an end of study visit within 30 days of your last dose.

### Conditions Module

**Conditions:**

- Ovarian Cancer

- Fallopian Tube Cancer

- Primary Peritoneal Cancer

**Keywords:**

- Epithelial

- Primary

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 63

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** CRLX101

**Intervention Names:**

- Drug: CRLX101

**Label:** Treatment Arm

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Treatment Arm

**Description:** q 14 days

**Name:** CRLX101

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Progression free survival at 6 months (PFS6) using RECIST 1.1

**Measure:** Progression Free Survival

**Time Frame:** 6 months

#### Secondary Outcomes

**Description:** Response Rate (CR+PR) using RECIST 1.1

**Measure:** Response Rate

**Time Frame:** 2 years

**Description:** Assessment of toxicity

**Measure:** Assessment of Toxicity

**Time Frame:** 2 years

**Description:** Analysis of ovarian tumor biopsies and ascites of the presence or absence of CRLX101 or the active drug, camptothecin

**Measure:** Analysis of biopsies

**Time Frame:** 2 years

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Histologically or cytologically confirmed epithelial ovarian, tubal or primary peritoneal cancer
* Measurable disease
* May have received up to 2 prior cytotoxic chemotherapy
* Life expectancy of greater than 3 months

Exclusion Criteria:

* Pregnant or breastfeeding
* Prior camptothecin, prior VEFG inhibitors
* Gross hematuria
* Chemotherapy or radiotherapy within 4 weeks of study entry
* uncontrolled HTN
* Receiving other study agents
* History of allergic reaction to compounds of similar chemical or biologic composition to topotecan or irinotecan
* Known brain metastases
* History of a different malignancy within the previous 2 years
* Intercurrent illness
* HIV positive on combination antiretroviral therapy

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Boston

**Country:** United States

**Facility:** Massachusetts General Hospital

**State:** Massachusetts

**Zip:** 02114

**Location 2:**

**City:** Boston

**Country:** United States

**Facility:** Beth Israel Deaconess Medical Center

**State:** Massachusetts

**Zip:** 02115

**Location 3:**

**City:** Boston

**Country:** United States

**Facility:** Brigham and Women's Hospital

**State:** Massachusetts

**Zip:** 02215

**Location 4:**

**City:** Boston

**Country:** United States

**Facility:** Dana-Farber Cancer Institute

**State:** Massachusetts

**Zip:** 02215

#### Overall Officials

**Official 1:**

**Affiliation:** Massachusetts General Hospital

**Name:** Richard Penson, MD, MRCP

**Role:** PRINCIPAL_INVESTIGATOR

## Annotation Section

### Unposted Annotation

#### Event: RELEASE

- Date: 2022-12-14

- Date Unknown: Unknown

#### Event: RESET

- Date: 2023-01-05

- Date Unknown: Unknown

#### Event: RELEASE

- Date: 2023-01-05

- Date Unknown: Unknown

#### Event: RESET

- Date: 2023-01-31

- Date Unknown: Unknown

#### Event: RELEASE

- Date: 2023-03-06

- Date Unknown: Unknown

#### Event: RESET

- Date: 2023-03-28

- Date Unknown: Unknown

#### Event: RELEASE

- Date: 2023-06-07

- Date Unknown: Unknown

#### Event: RESET

- Date: 2023-06-27

- Date Unknown: Unknown

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000000291

- Term: Adnexal Diseases

- ID: D000005831

- Term: Genital Diseases, Female

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000005833

- Term: Genital Neoplasms, Female

- ID: D000014565

- Term: Urogenital Neoplasms

- ID: D000091662

- Term: Genital Diseases

- ID: D000005184

- Term: Fallopian Tube Diseases

- ID: D000000008

- Term: Abdominal Neoplasms

- ID: D000004067

- Term: Digestive System Neoplasms

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000010532

- Term: Peritoneal Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M14850

- Name: Recurrence

- Relevance: LOW

- As Found: Unknown

- ID: M12974

- Name: Ovarian Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M1704

- Name: Carcinoma, Ovarian Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M8328

- Name: Fallopian Tube Neoplasms

- Relevance: HIGH

- As Found: Fallopian Tube Cancer

- ID: M13443

- Name: Peritoneal Neoplasms

- Relevance: HIGH

- As Found: Peritoneal Cancer

- ID: M3643

- Name: Adnexal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8943

- Name: Genital Diseases, Female

- Relevance: LOW

- As Found: Unknown

- ID: M2876

- Name: Genital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8945

- Name: Genital Neoplasms, Female

- Relevance: LOW

- As Found: Unknown

- ID: M17315

- Name: Urogenital Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8327

- Name: Fallopian Tube Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7

- Name: Abdominal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8886

- Name: Gastrointestinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7256

- Name: Digestive System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M13441

- Name: Peritoneal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T4352

- Name: Ovarian Cancer

- Relevance: HIGH

- As Found: Ovarian Cancer

- ID: T2189

- Name: Fallopian Tube Cancer

- Relevance: HIGH

- As Found: Fallopian Tube Cancer

- ID: T4354

- Name: Ovarian Epithelial Cancer

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000005185

- Term: Fallopian Tube Neoplasms

- ID: D000010534

- Term: Peritoneal Neoplasms

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M246

- Name: Bevacizumab

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

#### Submission Tracking

- Estimated Results First Submit Date: 2022-12-14

##### Submission Infos

- MCP Release N: Unknown

- Release Date: 2022-12-14

- Reset Date: 2023-01-05

- Unrelease Date: Unknown

- Unrelease Date Unknown: Unknown

- MCP Release N: Unknown

- Release Date: 2023-01-05

- Reset Date: 2023-01-31

- Unrelease Date: Unknown

- Unrelease Date Unknown: Unknown

- MCP Release N: Unknown

- Release Date: 2023-03-06

- Reset Date: 2023-03-28

- Unrelease Date: Unknown

- Unrelease Date Unknown: Unknown

- MCP Release N: Unknown

- Release Date: 2023-06-07

- Reset Date: 2023-06-27

- Unrelease Date: Unknown

- Unrelease Date Unknown: Unknown

- Version Holder: 2024-05-24
